Good morning, everybody. My name is Andy Chen. I'm the biotech analyst here at Wolfe Research and welcome to the second day, the first meeting of the second day of Wolfe's healthcare conference, and today we have Insmed, Roger Adsett, currently the Chief Operating Officer at Insmed. He's been with the company for many years and previously also the Chief Commercial Officer, based on my understanding, and that's also a very important role given that Insmed will be commercializing a big drug in the year 2025, so I guess for those who may not be familiar with the company, maybe Roger, you can give people, I guess, just a two or three-minute intro of the company and your focus on pulmonology. Yeah, perfect. Thanks, Andy. So I appreciate the opportunity to be here. For those of you who perhaps are not as familiar with the Insmed story, this year has been a pretty transformational year for Insmed. We like to think about our company as focused around four pillars, perhaps not the most imaginative structure, but the first three pillars are our products. So I'll give you a brief overview of each. And then our fourth pillar is our research pillar, where we have some novel research ongoing to feed the future for the company. And we just sort of lump that all into our fourth pillar. So the first pillar is Arikayce. As Andy alluded to, this was our first product that we launched. We launched that back in 2018, first in the U.S. This is approved for a condition, a rare pulmonary condition called NTM MAC. It's a lung disease that affects about 12,000-15,000 patients currently in the U.S. It's the only product approved for this condition. This year, we're guiding to $340-$360 million worth of sales. In the most recent quarter, we put up a little over $93 million in sales. It's about 18%, more than 18% year-on-year growth. So really, I think for now entering, what is that, our seventh year on the market, a really substantial growth for that product. We've commercialized that in the U.S., as I mentioned, as our first launch. But we also commercialized that in Europe and Japan. We think of those three regions as our key strategic markets: Europe, Japan, and the U.S. As I mentioned, this is approved for refractory MAC. What we're really excited about is the potential for expanding that indication into what we call all MAC. So rather than waiting for patients to be refractory and to fail on the guideline-based therapy for the first six months, we're conducting a trial to expand that indication so that when you get newly diagnosed, you'll be able to receive Arikayce as well, and that's something we call the Encore trial, and I'm sure we'll talk more about that, but we're looking to launch that indication and have results in the first quarter of 2026 from that Encore trial. Our second pillar is Brensocatib, and so Brensocatib is probably the most exciting asset for this year, and we had a very substantial readout, our Aspen trial in bronchiectasis this year, and so this is a product that we in-licensed from AstraZeneca. Arikayce is something we developed in our own lab, but Brento, we in-licensed. We did a phase two study in bronchiectasis, which was very successful, published in the New England Journal of Medicine. We followed that up with the Aspen trial, which is a very large trial. It was 1,600 patients worldwide. It showed, I think, pretty remarkable success. There's substantial excitement around this product in both the patient and the physician community. We were able to reduce exacerbations, which was our primary endpoint, across two doses, the 10 and the 25 milligram dose, by about 20%. But I think what was also very exciting. It's the first time we've seen that. There's nothing approved for bronchiectasis. But beyond that, I think what the KOLs are really excited about is we also saw on our 25 milligram a statistically significant reduction, or sorry, improvement in lung function. And so James Chalmers is our primary investigator, one of the premier thought leaders. And he thinks of that as disease-modifying potentially for this disease. So we're really excited about that asset. It attacks neutrophilic inflammation as a mode of action. So while bronchiectasis has typically been attacked by antibiotics and treating infections, this really treats the underlying inflammation. And so we're really excited about the potential for Brensocatib. Beyond bronchiectasis, which we will be filing with the FDA in the fourth quarter of this year, I will mention it has breakthrough status from the FDA and prime status from Europe. We're also exploring in phase 2 for chronic rhinosinusitis without nasal polyps and also hidradenitis suppurativa, which is a dermatological condition also we believe neutrophilic driven. So we're really excited about the potential for Brensocatib and can't wait to bring that to patients and the physicians. Our third pillar is a product we call TPIP. It's treprostinil palmitate inhalation powder. This is a prodrug of treprostinil. It also comes out of our labs. It's a dry powder inhaled product. What we've done is taken treprostinil, which is a well-known active molecular entity. This formulation is approved for both PAH and PH-ILD. We've made it into a prodrug. It gets cleaved in the lungs. What that results in is a sort of a sustained release of treprostinil. That is in contrast to the currently approved inhaled treprostinils, where you see this spike on the PK, which can be problematic from a side effect perspective, but also problematic from an efficacy perspective because it only lasts very short residence in the body. And so you need to take it four times a day, and you don't get any nighttime coverage for these patients. So we think that not only is our once-a-day formulation, that's very attractive for both patients and physicians, but we focus on bringing forward best-in-class, first-in-class therapies. And we really think that the potential from an efficacy and tolerability perspective for TPIP is pretty substantial. So we're able to get to higher doses than the currently approved TPIP. So compared to the DPI that's available from United Therapeutics, we can get to 40% higher doses just on our 640 microgram dose and 60% higher than their DPI, 40% higher than their nebulized formulation. We've seen we've released blended blinded data from our PVR, from our PAH study, which showed, again, this is across the whole spectrum of patients. So they can placebo plus the active therapy. We've seen a sustained reduction of 20% on PVR, which is comparable to oral treprostinil, just the therapeutic, just the active arm. We've seen actually some response, 50%, 60%, 70%, some of these patients have responded from a PVR perspective. Again, blended blinded, hopefully it's not placebo. If it is, maybe we should be taking placebo, but we'll see as we unblind that data, so we're really excited about the potential for TPIP in both PAH and PH-ILD. Hopefully that's a helpful overview. Yeah. So three major assets, right? One approved on the market already, one almost approved, and one that's very much de-risked in a way. So maybe we can talk about Arikayce for a bit. So you're going to have the Encore data soon. But maybe you can talk about the market opportunity a bit. So right now it's used in the later line, but you're hoping to expand into the front line. Can you talk about how big that front line setting could be? What's the market opportunity? Is it really a few-fold? Or if you can talk about the commercial potential a bit. Absolutely. Yeah, thanks, so we're really excited about the Arikayce, the potential in the front line setting, the early MAC setting. And just to review, the FDA has asked us to do a patient-reported outcome, so in order to get approval, most agencies around the world, in fact, most of the KOLs focus on culture conversion, so can you knock out that infection in these patients? And we were able to demonstrate that. But what the FDA focuses is on for patients, do you feel better? Do you function better? Do you survive better? So we qualified our PRO with our first part of our trial, which was the ARISE trial. Now, we also captured culture conversion data in that trial, and we were actually really very much encouraged by the results there. So not only do we have a PRO that we've endpointed, we've now agreed with the FDA will be the primary endpoint for the Encore study. So this is QOL-B, the Bronchiectasis Quality of Life Spectrum Scale with an eight-question measurement. And we were able to demonstrate that we were able to show a significant difference in our ARISE trial. But we also saw at six months an 80% culture conversion rate, which was sustained when we measured again in month seven. That contrasts that if you think about our initial CONVERT study. If you wait for patients to become refractory, that's about a 29% conversion. So you're much more likely, if you start earlier, to CONVERT these patients and knock out that infection. And we've been able to show that correlation with the patient-reported outcome that they actually feel better. The Encore study, as you mentioned, we'll have results from that in Q1 of 2026. It's a 12-month study. We're expecting to get those results there. But as you talk about the potential and the patient opportunity, so we're about 12,000-15,000 refractory patients in the U.S. currently. We think it's somewhere between 80,000 and 90,000 patients in the U.S. is the front line opportunity. Just anecdotally, I will share that we had a town hall meeting the other day in our company. One of our sales reps is getting impatient for our data to come out. She just shared with us that every day she gets questions from physicians who are asking, when will we have this front line data? Because he really is looking forward to using it with his patients in the front line setting. And we really think that the reaction to that ARISE data with that 80% culture conversion is really encouraging. That sort of changes the paradigm as to when they want to intervene. If you can intervene early and really knock out that infection for their patients, they're really excited about the potential to do that. Yeah, yeah. So that's the commercial potential. Can you also talk about the regulatory side? I think at some point in the past, you mentioned that you may be approaching the FDA to talk about potentially accelerated approval before even you have the Encore data, right? Can you talk about that a little bit? Absolutely, yes. So as I said, we were really excited about the ARISE data. And the KOLs also shared their enthusiasm with us. So the base case all along has been that we would expect that the FDA will want us to have the 12-month data, the PRO data, as well as the culture conversion data for the other agencies. But we were so excited about the data, we thought, well, why don't we ask and see if we can get an accelerated approval from that? So the FDA came back. And as we expected, we were hopeful. But as we expected, they said, no, we'd really like to wait for the Encore trial. So that continues. In fact, we can say that we've fully enrolled that trial now. So it is fully enrolled. We have 425 patients in that trial. And so we're still on track for that Q1 2026 readout and get that 12-month data for approval. Regarding your sales force, my understanding is that you hired 120 incremental salespeople in preparation for the Brensocatib launch. But right now, they're already calling on doctors to talk about Arikayce, right? So I know that you mentioned that your salespeople are impatient. But are doctors also impatient? Are they already asking you about Brensocatib even though you're basically selling Arikayce right now? Yeah, that's right. So yeah, so we have expanded our sales force, as you said. And so we've got about 185-190 patient sales reps out there, therapeutic specialists. And their charge is twofold. First, every one of them leads with Arikayce. So the first discussion is always about Arikayce. The interesting thing and the great thing about these two diseases is there's a huge overlap between bronchiectasis and NTM. So most patients, in fact, maybe all patients who have NTM, MAC lung disease, have bronchiectasis as well. So there's a huge overlap in the KOL, in the treating community, and in the specialists. And so we've expanded to cover all the pulmonologists in the U.S. So we are talking about Arikayce first line with them as our first position, not the first line indication. And then we're also charged with, as we did with Arikayce before we had approval, educating about the disease state. So we do educate about bronchiectasis. We talk about the inflammatory nature of this condition. And I will say that there is significant enthusiasm from physicians around Brensocatib. So they are anxiously awaiting the approval. But in the meantime, we are engaging very productively with our sales team. I have to say, I think we've hired just an amazing sales team to go out there and support Arikayce, but also to launch Brensocatib in the US. We had thousands of applications for the 120 positions that we added. So we were really gratified by the response for that. Got it. So no Brensocatib revenue yet. But what about Arikayce revenue? Because you have this new sales force. Should we be expecting an inflection upward in Q1, for example? Yeah. So as I mentioned, we've guided for this year to $340-$360 million. We put up $93.4 million in the third quarter. So we're not giving any guidance at this point for 2025. But we built into our forecast and our projections, we built into that expansion. So we knew we've been planning for success ever since Willow. And we put our plans in place to hire our customer-facing teams ahead of Aspen and pulled the trigger once we got the Aspen data so we were ready to deploy. So we've built that into our projections for Arikayce. But again, we feel very good about the opportunity for Arikayce and perhaps just a little bit more excited about the brensocatib opportunity. So maybe we can transition to Brensocatib right now. So Brensocatib most likely will be a bigger opportunity than Arikayce, even though it's your second asset. But given your experience on the commercial side, maybe you can talk about how fast that launch will be, right? I think you guided to $5 billion in bronchiectasis alone, right? In addition, you have other indications coming up. But in BE, how do you view the launch? Should we be thinking about Arikayce as an analog? Because I think Arikayce also had a very fast launch at the beginning. Or should we be expecting something slower just because I think there's a Medicare tilt in BE? So you won't have official coverage for a while, right? So maybe you can comment on that a bit. Yeah, absolutely. So yeah, so as you mentioned, Arikayce took off really quite well. We were very pleased with that launch. It was a top 10 rare disease launch at the time. We've got the same team who are working on Brensocatib. It's a much larger opportunity for us, to be frank, right? So as we think about the opportunity and the uptake for Brensocatib, we've looked at not the Arikayce analog, because we're talking about in the US, 550,000 diagnosed bronchiectasis patients. And we had 12,000-15,000 for Arikayce. So it's quite a much larger opportunity. We looked at some other analogs. So Dupixent is one we looked at. We looked at Tyvaso. We looked at Fasenra and Ofev as other opportunities. And we think that in the first two quarters, we're looking at benchmark would tell us if we're doing really well along those analogs. We're looking at the high 10s, high double-digit millions of dollars. Now, this is, of course, going to be dependent. This is the first two quarters dependent on when we actually get approval and we're able to get launched. We're looking at mid-next year for that approval if all goes well. Then as we think about the months three through six, that's sort of the $500 million-$600 million as the first full 12 months on the market. That's the sort of analog that we're thinking about. As you mentioned for the Medicare coverage, it actually reflects the split between Medicare and commercial is actually pretty similar to Arikayce. It's not unusual. In fact, most products, you don't come out with formulary status. You have to go through this medical exception process. Medicare has to review within the first 90 days of your approval. In the meantime, it's a pretty straightforward process to get covered. It's to work with the physician to just attest why this patient will need this therapy for their medical condition, so that's what we expect to launch with. We do have our managed care team already intact. They're having product education information sessions with the payers, and we do expect that we'll be able to get to our ambition is to get to an attestation that the physician will match the criteria for the Aspen trial, and we'll be able to get reimbursement for Brensocatib using that methodology. And within this bronchiectasis population, my understanding is that the diagnosis rate is very low right now because there's no approved therapy. So why bother diagnosing these patients correctly, right? So assuming that Brensocatib is approved on the market, my expectation is that the diagnosis rate will go up. But how fast will it go up? And will it really go to 100%? I don't know. Can you maybe comment on that? Yeah. So let me push back just a little bit because I don't think it's low diagnosis currently. So we have about 500,000 to 550,000 diagnosed patients in the U.S. currently. So that's a pretty substantial market. They're already diagnosed. They already have a diagnosis code in the databases that we've searched. And that's how we've sized our sales force to cover the pulmonologists with those patients. We have about 600,000 patients in Europe. And we're estimating about 150,000 patients in Japan. So we've got over a million patients worldwide already diagnosed. But I think where you're going with this, and this is what is really interesting about this opportunity, is there's a significant number of patients that the medical community believes, particularly within the COPD population, that actually have underlying bronchiectasis. So they're co-diagnosed with COPD and bronchiectasis. So the literature is all over the place. They say anywhere from 4%-54% of COPD patients might have underlying bronchiectasis driving their symptomatology. If we talk to the KOLs, sort of it varies from practice to practice. But they seem to be landing around this 20% mark as to potential. If you do a CT scan, which is the gold standard for diagnosis, then you might show that amount of patients that actually have the bronchiectasis driving their symptomatology. So we're really excited about that opportunity. As you mentioned, if you're doing a CT scan, there was not the rationale to do that other than if you're, well, this patient's really sick. I need to see if I can help them. But without an approved therapy for bronchiectasis, there wasn't really a lot of driver to go and do that CT scan. We think that with the approval of Brensocatib and the first approved therapy for bronchiectasis, we think that there will be an initiative from physicians to actually investigate at least some of those COPD patients that are continuing to have symptoms and they're not responding adequately to their therapy, so we're excited about that opportunity as well. I think in your pipeline, I think in the past, your company talked about maybe another DPP-1 molecule, maybe a next generation. Is this a replacement for Brensocatib? Is it an upgrade? Or is it just for future indication expansions into non-bronchiectasis indications? Yeah, thanks. So as I mentioned, we in-licensed the Brensocatib from AstraZeneca. And so we have worldwide rights to all indications for Brensocatib. But COPD and asthma are carved out of that. So neither company can pursue those indications. So what we wanted to do is, as we think we've unlocked this neutrophilic inflammation platform, is to expand into different indications, the first two being CRS and then without nasal polyps and then HS. But there are other neutrophilic inflammation indications that we think that we could pursue. We just mentioned COPD and asthma as potential. But also, if we think about something like rheumatoid arthritis, that might be something that would be interesting for us to pursue as well. And so we've decided that what we wanted to do, and we did this after we saw the Willow data, is we wanted to build a stable of DPP-1 inhibitors. Now, it's not so much as improving on Brensocatib because Brensocatib is a pretty impressive compound with the efficacy and the safety that we've seen. But it's getting different molecules. If you think about the IRA and the incentive to pursue different disease states with multiple products as opposed to stacking the indications onto a small molecule, then that's something we thought made a lot of sense to us. So as we think about the additional inflammation opportunities that we want to pursue, we want to do those with novel DPP-1 inhibitors. The ideal would be to match the characteristics and the different enzymes that are inhibited by DPP-1 to the specific disease state if we can do that. But that's where we're headed, is really about indication expansion rather than replacing Brensocatib. In comparison versus Arikayce, for example, Arikayce is kind of special because the Japanese market is pretty big compared to other drugs. Is there something special about brensocatib and the ex-US market? Are there unique challenges or opportunities within the ex-US market for brensocatib? Yeah. So we're really excited about the potential. I think it's interesting you mentioned Japan. And what we've seen within our sub-analysis that we just released at CHEST for brensocatib and the Aspen data is we saw a really robust response for patients of Asian ethnicity. So either patients from Japan or patients who self-identify as Asians, we saw actually a reduction of around 60% of exacerbations. So we think our Japanese team saw that. They were very excited about the potential there. We don't understand why, to be quite frank, why there's this response. But we've seen it across. There's two other companies that are developing DPP-1 inhibitors. There's a Chinese company called Haisco. And Boehringer Ingelheim is also developing a DPP-1 inhibitor. And we looked at their data. And it seemed like the Asian population was also responding in a better way there. So it's consistent across these DPP-1 inhibitors. So we think the effect is real. We'd like to understand a little bit more why that is. But we think that that bodes really well for the opportunity in Japan if we're able to really reduce those exacerbations even beyond what we saw from top-line data within Aspen. Yeah, yeah. And then moving to TPIP, your third product, which in our view is also kind of de-risked, there are two indications here. There's PAH. There's PH-ILD. There are, I guess, advantages and disadvantages of the two markets. One is more crowded. One is not, and I think one is tougher to treat. Can you maybe talk about the opportunities within each? I think Insmed previously talked about maybe a $2 billion opportunity. What's the split? Which one is the bigger opportunity here? Yeah. So we also feel very excited about TPIP and the potential in those two indications. So if you think about the split for patients in PAH and PH-ILD, I think PH-ILD is about 40% larger than the PAH population. We haven't given any guidance on how we think the revenue splits out for TPIP. But that gives you, at least from a prevalence perspective in the U.S., as to how things shake out. Although interestingly, I think the PH-ILD, Tyvasco is the first product approved there, the only product approved there. And we'll see if that expands the indication as well as their launch progresses, as you might see more patients being identified and treated. But both of these diseases are devastating diseases, right? PH-ILD is a death sentence. PAH also, these patients have very high near-term mortality. So really quite sad for those patients who are facing those diseases. And I think the unmet need is quite high. So as I mentioned, the PHILD, we did a phase 2 trial that we read out earlier this year. This was primarily a safety trial. So very small, 39 patients. And we saw very good safety. We saw we were able to get to those higher doses of 640 micrograms within these patients. And interestingly, we saw in one of our secondary endpoints, and this is nominally statistically significant, but we were able to see a difference even with that small amount of patients on clinical worsening. So we were really encouraged about PHILD. We expect to kick off a phase 3 in the second half of next year. We'll be talking to the FDA about that design. And then PAH, I mentioned the blended blinded data. We think that if everything holds up really well, that we'll be able to hopefully show a really significant impact on PVR. We'll also be measuring the six-minute walk test. And again, we're able to get to 85% of the patients, I think, have been able to get to that 640 microgram dose. Really encouraging was the doctors. When we talked to them, our safety monitoring committee, they encouraged us to really move to higher doses than even the 640. And so in our open label, we'll be making available going up to 1280 micrograms. So what the doctors tell us is a very well-known dose response curve. The impediment has been the tolerability of treprostinil. If you can solve that and get to those higher doses, then you're going to get better efficacy out of this molecule. So we're really encouraged about that. So PAH, we're ongoing with our phase two trial. We're over 90% enrolled currently. We expect to have results in the second half of next year. And then we'll be assuming all those goes well, we'll be able to move into phase three with PAH as well. In my conversations with investors, most people ask about brensocatib. Most people don't ask about TPIP. Why do you think this might be underappreciated? I mean, what's the misunderstanding here? Yeah. Or Or is it just because brensocatib is going to be such a big drug? It's in the spotlight. Is that why? I think that's part of the reason. Honestly, I mean, our CEO, Will Lewis, he always talks about TPIP as the most underappreciated asset in our pipeline. Brensocatib is an enormous opportunity. It kind of takes all the air out of the room when we start talking about that. But I think what we wanted to accomplish by releasing the blended blinded PBR data was really to have the physician community understand this is not just treprostinil, right? This is a pro-drug. And there's really differentiated efficacy and safety outcomes that have potential from this drug. So we wanted to encourage the enrollment in the trial. And once the physicians and the investigators saw that data, they became much more excited about it than if you just think it's another treprostinil. I think that as we have more data and as we unveil that data, I think the excitement will grow around TPIP and the potential for this molecule and these patients. There is also a hidden fourth pillar. I think previously Insmed talked about how you may have new assets, a new clinical asset around year end or maybe Q1. Can you maybe provide some color here? Yeah, absolutely. So that fourth pillar of the research, everything is sort of into our research pillar. So we've got a variety of platforms that we're looking at. And so one of the things that we're focused on is gene therapy. And we've openly talked about a novel approach with an intrathecal administration to treat boys with Duchenne muscular dystrophy. And so we're progressing along those lines. So stay tuned more to come on that. OK, OK. So thinking about 2025, looking ahead, you're going to have the Brento launch, right? You're going to have more TPIP data. Maybe we're going to have some DMD news. Anything else that you want to highlight for investors? Yeah, absolutely. So we'll be starting out PH-ILD phase 3 next year, PAH data in the second half of next year, as you mentioned, brensocatib launch, hopefully the approval on the launch next year, filing for Europe and Japan to come thereafter. We expect to have CRS without nasal polyps data by the end of next year, and then we'll be enrolling our HS trial for brensocatib as well, so a lot of catalysts coming up for 2025. Got it. Thank you, Roger. We have about 30 seconds if there are any questions from investors. No questions, so Roger is going to be around for today, and I think a whole day of meetings lined up. Yes. All right. Thank you, Roger. Thanks for your participation. Appreciate it. Thank you. Thank you.