Insmed Incorporated (INSM) Earnings Call Transcript & Summary

Great. Welcome, everyone. My name is Jess Fye. I'm a biotech analyst at JPMorgan, and we're delighted to be continuing the 44th Annual Healthcare Conference today with Insmed. First, you're going to hear a presentation from the management team, and then we're going to go into some Q&A. [Operator Instructions] So with that, let me pass it over to the company CEO, Will Lewis.

Thank you. Thanks, Jess, and thanks, everyone, for joining us today. I want to start out the presentation with the call out to our forward-looking statements. The forward-looking statements mentioned here in our public filings should be something that everyone reviews carefully. Before I begin the presentation, I'd like to take a moment to talk about what drives us at Insmed, and that is our impact on patients and to highlight that I'm going to read a quote from a physician that we recently got in regards to the BRINSUPRI product that is now on the market for non-cystic fibrosis bronchiectasis, goes like this, "I see a patient who is a mother of 2 teenagers with a history of bronchiectasis since her 20s. Her chronic cough has kept or from attending sporting events, plays, movies, et cetera. She doesn't sleep most nights because of the cough. She has broken ribs due to it. She even has to work from home because her cough causes incontinence. After 4 weeks on BRINSUPRI, her CAT score went from a 32, which is a terrible score to a 6. She doesn't cough anymore. Her FEV1 increased 15%, she broke down in tears in my office. No more antibiotics, no more IVs, no more chest physiotherapy." Now I want to emphasize that we see these stories like this is inspirational and not necessarily representative of a typical patient or our clinical data, but it's extremely gratifying to hear that kind of an impact of the medicine that you see identified here in the upper left-hand corner. Insmed is a company organized around 3 therapeutic areas, respiratory, immunology & inflammation, and neuro & other rare. And in the upper left-hand corner, you see BRINSUPRI, which is the recently approved product for the treatment of non-cystic fibrosis bronchiectasis, the first ever approved for the same. ARIKAYCE, which is approved for the treatment of refractory MAC lung disease, the first ever approved for that disease. And beneath that, highlighting TPIP in its 4 indications we intend to pursue, the first of which PH-ILD is already in Phase III. PAH is going to follow shortly, followed by PPF and IPF in the second half of this year. Beneath that, we identify INS1148, which is a monoclonal antibody we recently acquired. And then we have DPP1 other generation molecules that will be targeting other diseases. In immunology & inflammation, we highlighted a number of things we're targeting. Brensocatib we'll be looking at HS in this space. We'll have more to say about that. We can look at our other DPP1 that's going to be entering the clinic this year. In this case, for rheumatoid arthritis and irritable bowel disease. We have next-generation products, which are deimmunized therapeutic proteins, Uricase for the treatment of gout, and that's something that we believe will be able to evade the immune system's response to Uricase as it's currently is a problem that, that program faces. IgG protease will similarly be deimmunized and launched. We have other applications in the I&I space for INS1148, and then we have a novel mechanism of action within the clinic right now -- pardon me, within our internal research right now that we think could be as impactful as DPP1. Finally, I'm very excited to talk about neuro & other rare. The first 2 identified here are gene therapies to treat Duchenne muscular dystrophy. We're already through our first cohort there and have 2 other cohorts behind it, which have already begun to enroll patients and we are now enrolling patients in our ALS study. Beyond that, we see a gene therapy that will enter hopefully, IND approval for Stargardt and then several other programs that are earlier in development. But collectively, you see our ambition to develop first or best-in-class therapies with each of these programs supported by further research and business development. Our company has gone from focusing on the 2 products in the upper left hand of respiratory to the entire collection that you see here today, and it is indeed an exciting time for Insmed. The last 18 months has seen our market cap increase on average $2 billion per month every month for the last 18. As we look forward, we see this collection of different milestones, both commercial and clinical that will be reading out, and this is what gives us encouragement that we will continue to be able to have impact in driving shareholder value. that shareholder value is identified here on the left-hand side of this slide. On the right-hand side of the slide, we try to highlight the different areas that will hopefully drive future value. We like to think that if we take care of patients, we'll take care of our investors as a consequence. And many of these compounds and trial readouts here represent first or best-in-class therapies that we should be able to either provide proof of concept or full approval for. Let's take a deeper dive into the first of the 3 therapeutic areas, which is respiratory. The lead program here, BRINSUPRI has just had what can only be described as a stellar full fourth quarter. It's our first fourth -- our first full quarter of performance, and we added 9,000 patients in that quarter, which gives us a cumulative total of more than 11,500 since the launch in August of last year. We have now more than 4,000 prescribers who are writing for this drug. It's very important that everyone understand that when we look at these 2 numbers, the 11,500 patients, that's from a targeted total of 250,000 and the 4,000 prescribers is from a targeted total of 27,000. So as impressive as these numbers are, they are just the beginning of a very long journey. On the left-hand side, the consequence of this is we put out very impressive revenue numbers for BRINSUPRI in the fourth quarter, $144.6 million. To put that into perspective for you, DUPIXENT's first full year of launch this number is higher than their fourth quarter from that first year. There's a lot of momentum behind this launch but there's still a lot more that we need to understand in order to gain a real confidence of where this is going to go and how high up is up. And those things include out-of-pocket reset dynamics. It always haunt the first quarter of the year for every drug, regardless of what it is. And the possibility of the clarity around insurance programs and how they will authorize or not, the use of this drug. I will tell you right now, we have had very good success in the market access arena. We expect that to continue, but it is something we're going to be watching very carefully. We called out inventory stocking. It was around 9% of Q4. We are contractually bound with our specialty pharmaceuticals -- pharmacies that they are not able to stock more than 2 weeks of inventory. So this number we don't expect to grow or be material as we move forward. It's important to remember that the other product we have approved ARIKAYCE also performed well this last year. We beat our guidance, which was raised during the year. And this year, we are targeting $450 million to $470 million for the full year. This represents continued growth in the eighth year that this drug has been on the market. We had particularly strong performance, as you see on the left-hand side, from international, which is Europe and Japan, and we expect that to continue. The next clinical trial readout will be ENCORE. This is the expansion opportunity for ARIKAYCE to treat frontline MAC patients. There is a current total addressable market that we target of around 30,000 patients. Should this trial be successful, that will increase to in excess of 200,000 patients. If you remember, we're targeting $450 million to $470 million in revenue this year from just the refractory market, one can imagine that the success going into the frontline market will bode very well for the future growth prospects of this program. Importantly, for both refractory and frontline MAC, there is nothing approved to treat this condition. So this meets our threshold of being first or best in class. We look at our next program in respiratory, which is TPIP. This is treprostinil palmitil inhalation powder, this is a 16 carbon chain appended to treprostinil by an ester bond. And with that dry powder formulation, it enters the body when it's inhaled with a single breadth and the esterases in the lung cleave off that ester bond and release the active drug. This has shown very good data in PH-ILD and PAH in Phase II, best-in-class. Clearly, very efficacious in terms of pulmonary vascular resistance as well as NT-proBNP and 6-minute walk benefit. And so our Phase III study is centered around those metrics and objectives. For PH-ILD, this program is already underway. It's called the PALM-ILD study. It initiated in December of last year. And for PAH, we expect to initiate that Phase III program imminently. PPF and IPF will begin later this year once we've had a meeting with the FDA and clarified what that will look like, but we're excited to be announcing that TPIP is going to be pursuing 4 Phase III programs in parallel and the opportunity that this would represent in terms of patient impact, because of the clinical data we produce to date, should it be replicated, is profound. This program, I like to say is every bit as exciting and promising as BRINSUPRI is and bronchiectasis is and where it could go remains to be seen, but certainly, the early data have been very, very encouraging. Let's talk a minute about INS1148. This is a program we in-licensed recently. It's a first-in-class therapy monoclonal antibody for the treatment of both respiratory and I&I diseases. Essentially, what this does is it targets stem cell factor III and the c-Kit signaling pathway that's associated with inflammatory disease Importantly, it does not impact stem cell factor 220, which is involved in homeostatic and tissue healing. The consequence of this, we believe will be that this program will be very effective in these diseases we're targeting initially ILD and moderate to severe asthma. And we hope that the data that has been available so far, which is an atopic dermatitis which showed a very benign safety profile and very clear efficacy will be replicated in these disease states. We'll have more to say about this program once we get, if you will, our arms around it through later in the year, but this is a very exciting addition to our repertoire. This is a snapshot of the swim lane just in respiratory. And here, you can see a broad collection of assets which are first or best-in-class all along the development time line. And on the right-hand side, the catalysts that are associated with each of them. You can see it is going to be a very busy year ahead for the respiratory therapeutic area. As we turn our attention to immunology and inflammation, the first readout we'll have here is in the second quarter of '26, the so-called CEDAR trial. This is looking at BRINSUPRI in the treatment of hidradenitis suppurativa or HS, which is a dermatologic disease or condition, we're going to be targeting AN count as the primary endpoint and a clear win in this trial that would encourage us to move into Phase III would be a 20% reduction in AN count versus baseline, a home run or, if you will, a World Cup win, as is more timely, is a 40% reduction in AN count versus baseline. We will be looking at the high score as well. For those of you who are familiar with this disease state, that takes longer to see impact in certain of its measures. And so that will be done at the end of the 52 weeks that this study will run. This is the balance of the pipeline in I&I. It's not as robust as respiratory, but there's some very exciting programs in here, including our next-generation DPP1s going into RA and IBD. Many of you are familiar with the CRS study we executed that did not work, that we reported that in December. That study has been shut down. That was with a DPP1 BRINSUPRI -- rather brensocatib targeting that disease state, but it was a clear miss and from that perspective, we consider the trial of success in answering the question of whether or not it's going to be effective. It's important to note that for both CRS and HS, there are no animal models available for those diseases. So it makes it very difficult to predict whether or not your particular drug candidate is going to be efficacious. For RA and IBD, it's different. There are available animal models, and we have tested the INS1033, this DPP1 in both of them. We indeed published our RA data from our brensocatib test in that model. It's very encouraging, and that lays a very strong round work for our belief that this is going to be a successful development program. We have another -- other programs in this area, and we certainly expect to keep our eyes out in the BD arena to see if there are ways we can augment here. As we turn to neuro and other rare, I mentioned at the start, both DMD and ALS. These programs are now up and running. In the DMD space, this is a novel approach. We're using intrathecal delivery for the treatment of this condition, which is counterintuitive because why would administering this gene therapy through the spinal cord result in effective transduction in muscle and cardiac tissue, but in fact, that is what we saw in animal model data. This is an incredibly exciting program because by virtue of going through the intrathecal delivery route, we avoid the IV challenges of first pass effect going through the liver or the majority of the virus is weeded out and creates oftentimes an immune response that can be very dangerous to the patient in question. Indeed, several young boys have lost their lives to the attempt of using this route. We're pleased to say that we are focused on the intrathecal route, and we think that will allow us to dose lower and be safer while still getting comparable or better efficacy, and that's the objective of this study. It's very exciting to be into cohort 2 and cohort 3 already. There's a lot of enthusiasm in the community for this program and you're going to be hearing more about it as we go through the year. Importantly, we are not using weight-based dosing, and that is significant distinction from other companies that have programs in this arena. Similarly -- and that's the ASCEND study for your reference. In ALS, we have the so-called ARMOR study, which initiated in the fourth quarter of last year. We are studying both SOD1 and sporadic patients. In our preclinical work, we took note that in the cell assay, we were using 7 of 10 cells that were taken from sporadic ALS patients were responsive to this treatment. That is an incredibly encouraging sign and is something we took to the FDA, and they agreed that in this study design, we could go after both sporadic and SOD1 patients. So in Cohort 1, we're actually starting off with sporadic patients. And we're super excited because as everyone is probably well aware, this is an absolutely devastating disease with nothing really available that makes a material impact, there's a lot of work still to be done here, and we want to hopefully be able to contribute to that. But we're very excited about these programs, and they'll continue to enroll this year. We haven't yet decided when we're going to begin to share data. We've obviously seen some of the DMD biopsy data already but there's more to come, and we want to make sure we have a complete data package when we finally bring this forward for everybody to evaluate. This is a snapshot of the neuro & rare therapeutic area pipeline beyond DMD and ALS. We have Stargardt. We have another gene therapy target we're considering right now. It's advancing. And then we have 2 other programs coming out of our Cambridge England operation for Ataxia-Telangiectasia and AOA1. This is using the synthetic rescue technology that is specific to that research site. Collectively, these 3 therapeutic areas are extremely exciting, and we will look to augment modestly through business development as we move forward. This comes built upon financial strength, as of the end of September, we had $1.7 billion of cash. We've talked about the guidance for this year for ARIKAYCE of $450 million to $470 million. And while we're not providing guidance for BRINSUPRI because it's too early in the launch, to be able to do that accurately, we feel very confident that we're off to a very strong start and that will continue. We're looking to take the capital that we have and look to deploy it against all these commercial and clinical opportunities as well as additional business development opportunities that we see suitable for in-license or acquisition. Behind all of this is the greatest strength of the company, which is our culture. I am incredibly proud of what we collectively have built at Insmed in this respect, and it has been recognized externally. We're now 5 years in a row, the #1 on the science top biopharma employer list, that's a feat that's matched by only 1 other company called Genentech. Everybody at the company is extremely excited about the work we've been doing. Often, people talk about the dramatic change in the company over the last 18 months. We like to say it's an overnight success, 13 years in the making. But the point is that we have assembled really a first-class collection of employees who are very motivated to help patients and as a consequence, drive value for our shareholders. So let me just end by summarizing the momentum that we had in '25 was hard to match. We're aware that sets a higher hurdle for us. And honestly, we welcome it. We are very driven to continue to see the success of BRINSUPRI. This is a first in disease approval and a first in mechanism approval. We're very excited to bring that forward. The strong start we've had to date, we hope is indicative of what's to come. with international launches to augment that this year. We are already approved in Europe. We will launch there in the first half of the year, along with the United Kingdom is our expectation. And then in the second half of the year, Japan, where we both already have commercial infrastructure in both regions. The 3 therapeutic areas I reviewed give structure and direction to where we intend to deploy our resources and our managerial attention and we're super excited to augment those through business development. The next 18 months will have more events commercial and clinical than the prior 18 months, and we know what that represented in terms of our value creation. So we're hopeful to be able to build on this momentum for the benefit of shareholders by benefiting patients. And with that, I'll stop, and we'll go to questions. Thank you.

Great. [Operator Instructions] Maybe just picking up where you left off, you mentioned the therapeutic area structure and business development, is that a priority across all 3 areas or more of a priority in some than others? And what type of deal structure are you kind of interested in right now?

Well, it's interesting. I think the deal we just did mirrors the one we did for DPP1 which we paid, I think, $30 million upfront for. This one, we paid $40 million upfront. Those are no-brainers. I'll do those all day long where you have a novel mechanism of action that targets multiple potential diseases and where we think scientifically we have seen evidence for why it will be effective and safe. Oftentimes, a little differently than perhaps the rest of the market does, which is why they're available at these inexpensive levels relatively speaking. I will do those all day long in any of those therapeutic areas. Part of the reason we did the architecture we did was to enable us to not only modularly add on new programs within each therapeutic area, but also to consider more ambitiously additional therapeutic areas we might target. We don't have anything on the agenda right now. But I would tell you, we would not limit ourselves to just the 3 therapeutic areas if we found something truly compelling Insmed views itself as being on a mission to create a self-sustaining biotech company. We've got a lot of growth within the pipeline already, but you want to do business development when you don't need it, that's something I'm a big believer in, and we've done that throughout our history, sometimes to the chagrin of some of our investors who would like to see us focus only on what's in front of us. But my belief is you've got to get there and you have to have development across the spectrum because inevitably, drugs are not going to work in certain diseases or they'll work, but they'll be meager. And I'm not interested in bringing forward a drug that isn't highly impactful on patients because when you do that, it makes the rest of the process so much easier.

Okay. So I guess related -- the third 1 is rare and not necessarily -- it's not necessarily like 1 therapeutic area, right? So we got a question here on the portal that was about the rationale for entering the retinal space with Stargardt disease. And what Insmed's aspirations are as it relates to becoming a big player in retina?

Yes. So I think right now, we call it neuro & rare and that's sort of a catch-all for the stuff that is coming out of our research labs that might be off of a platform that is related, but not disease related. So Stargardt is a good example. That's another gene therapy construct. There, we're harnessing a different kind of clinical technology, scientific technology, which is really fascinating. It's RNA enjoining. One of the limitations of gene therapy is the size of the gene cassette. And so what you can put inside a viral vector that gene cassette can't get bigger than that viral vector. That's why in the treatment of Duchenne muscular dystrophy, what's used is microdystrophin. It's not a full-length dystrophin. You can't make the full-length protein because what you can fit in the viral vector is constrained. RNA enjoining allows us to send in 2 viral vectors, 2 transgenes, which are then rejoined intracellularly and then read by the cellular mechanism to produce the protein that is therapeutic -- thought to be therapeutically beneficial. This is really cutting edge science, we've seen very good progress so far. The first place we're going to be applying it is in Stargardt because we'll be able to make the full-length protein. And we think that will be hopefully very impactful and safe, it's hermetically sealed in the eye so that makes it easier not to have to worry about ancillary implications from that approach we're taking. But we are also doing work in Duchenne muscular dystrophy for mid-length dystrophin. And as excited as we are about our microdystrophin program, our ambition here is to really impact this disease state. And the way we're going to go about doing that next is by using RNA enjoining to create a mid-length dystrophin and produce that in the hopes that they will be even more beneficial for patients with that devastating disease.

When can we start seeing some of that data, clinical data?

I don't know. I would say we're not going to put that data out. We might put a little bit out in '26, but probably '27. And the reason we say that is because, look, we've seen biopsy data. We know where we're going with the preclinical data. I am well aware that from the point of view of the investment community, the vast majority of the energy is focused on BRINSUPRI and ARIKAYCE and TPIP and the expansions that surround those 3 programs, and those are incredibly significant and important value drivers. But I am here to tell you that it is just the beginning, within Insmed for many years, we did these acquisitions 4, 5 years ago. We have been percolating the next gen of compounds that will be first or best in class. And the next place we're going to go is using gene therapy in DMD, ALS, Stargardt, possibly RET other places. So there's a lot out there for us to still do but each 1 of these programs needs to be first or best-in-class, and we need to convince you of that. And the way we're going to do that is not by putting out the first piece of data we have, but by building a mosaic that makes it very clear how the drug is in terms of its safety and its efficacy. And that includes both biopsy measures plus NSAA measures which are the ability to actually impact the patient's functionality. And we think that collective data is important for people to make their assessment. ALS is a little bit different. We'll have to look at what kind of data we unearth there as we move forward and how quickly the patients enroll but I am incredibly excited about this. We have several scientists who have devoted their entire lives to the treatment of this disease, and they are over the moon that we are now treating patients with this therapy because the preclinical animal data was just unbelievably exciting. When that data comes out in humans, we will share it. And hopefully, it will be just as compelling as it was in the animal models. That's probably not until '27.

So coming back to TPIP, a multipart question. One, you mentioned ramping manufacturing to support the IPF and PPF trials. What do you need to do to start those trials? Second part would be you've got multiple trials, multiple indications. Should we think of any of those as being kind of faster to recruit and get to data than others? And lastly, within the Phase II PAH, open-label extension data that I think we're getting later this year. What should we be looking out for when that data comes out?

Yes. So on the manufacturing side, we just need to make more drug. We have just added 2 massive Phase III programs to our original ambitions, and that's going to require more manufacturing. It's not a hurdle, we will be challenged to clear, but it is just a logistical reality we have to cross. At the same time, we also want to have dialogue with the regulatory agencies about the design of the IPF and PPF studies so that we're really clear on what those studies need to deliver in order to achieve approval because these are all Phase III studies for TPIP, it's registrational work we're doing. So we want to make sure that, that's clear, particularly because we haven't done Phase II or Phase I work in these areas prior, PPF or IPF. So once we have that clarity, I think we'll move as quickly as we possibly can to kick off those trials. But we're big believers in going slow to go fast as it relates to registrational study work. The second question related to?

Which of those indications or trials might go faster...

Which 1 can go faster in terms of enrollment. So ILD and PAH, we have data for. And just to refresh everyone's recollection, ILD data showed improvement in time to clinical worsening, improvement in 6-minute walk, it was a very small study, and it was really intended to be more of a safety study than actually an efficacy study. So the fact that we saw that was incredibly encouraging, so encouraging that it was discounted at the time. It also happened to come out right around the time of our ASPEN Phase III results. So to be honest, nobody really cared. But if you look at what happened in PAH, we had a 33.9% reduction in pulmonary vascular resistance, which is hands down to the best of our knowledge, above anything else in the prostanoid class. No one's ever come close to that. That is, in fact, comparable to sotatercept for PAH. So that result with a once-a-day dry powder formulation that covers patients for 24 hours is incredibly impressive. And it suggests that the ILD study was, in fact, as strong results as it appeared to be. Now these data getting into circulation have certainly raised the interest and appetite of the key opinion leader community in PAH to use this drug for the treatment of their patients. So we expect that our enrollment will be faster than it was in Phase II. We won't know that until we're into it a little bit. And since we just started the ILD study, and we'll shortly start the PAH study, it's going to take us a little while to get a sense of the tempo but we're very excited about what that could mean IPF and PPF are further down the line second half of the year ideally. And if that's the case, we'll have a better read on that once we get going, final question?

OLE data?

OLE, second half of the year, PAH open-label extension data, we will be looking at patients, some of whom may have titrated up even further in dose and others for all of them will have 6-minute walk data updated NT-proBNP data, which is a great correlate to impact on pulmonary vascular resistance and of course, safety data. It's important to understand that the doses we were looking at in Phase II were up to 640 micrograms, which is well above the highest dose you can get to with any other form of treprostinil. We then were told by our Data Safety Monitoring Board and the FDA that it is okay to go to double that level. So our Phase III studies will be targeting up to 1,280 micrograms of drug. In the open-label extension, we permitted patients to go higher if their physician thought it warranted it. So we may have some insight into what a higher dose above 640 would look like for these patients in terms of safety and efficacy. But this is incredibly exciting to be able to go that high with this drug for what is a fatal disease and have impact that at the Phase II study showed was a 33.9% PVR reduction that bodes very well for the higher doses, potentially having even more impact. And that would be a profound change for these patients.

So BRINSUPRI, what were your kind of key takeaways from this kind of initial launch experience? And how are you thinking about the growth and market penetration in the coming year?

The reason I started out with that quote from the patient that we got from one of our physicians is that that's not the only one we've received. We've received a number of these, and it's very encouraging. It's very exciting. It's inspirational. Obviously, it's not necessarily indicative of what every patient experience is. But the point of this is when you first launch a drug, particularly 1 that is for a disease like bronchiectasis, this disease has been around since '18, '19 with nothing approved to treat it. Every company that has tried has failed along comes the unknown Insmed, and we have success with this DPP1 inhibitor. And so the reticence to engage with this drug right out of the gate is a little bit there, right, new drug, new mechanism, and physicians are probably going to try it on 1 or 2 patients and see what happens. The immediate feedback loop that they get after a month or 2 of these patients being on drug, if it contains these kinds of anecdotes, is incredibly powerful to the further prescribing of the drug much more broadly and to the ultimate appetite of the patients to seek out the drug when they go in to talk to their physician. So we see this as the beginning of a potential virtuous cycle that will support the expanded use of the drug, encourage the physicians to continue to go and write more prescriptions. And we are starting with 4,000 physicians who've already written a prescription, out of 27,000. So we have a lot broader to go, and I'm confident we'll get a lot broader in the coming quarters. Importantly, those physicians will then hopefully write more prescriptions, which is to say, we'll increase our depth of prescribing behavior. So as those things expand, the opportunity for this drug to really deliver value to patients is going to be self-evident. And I hope those stories circulate because if they do, that's the big learning from this launch, not only do the patients experience the benefits that we're seeing in Phase III, but they are feeling better. And that's what we've heard from some of these anecdotes. It's not surprising. If you look at the secondary data secondary endpoints from the Phase III study, we had a very nominally statistically significant value for quality of life, bronchiectasis questionnaire or patient-reported outcome on how they felt on the drug. It was in the hierarchy below something that missed. So we can't say it's statistically significant. But if you look at the data, it's very encouraging. And to hear the real-world experience match that is very powerful. That means we think this will pick up momentum as patients and physicians talk to 1 another. And that's probably the biggest takeaway from the early days of the launch.

Okay. Can you talk a little bit more specifically about what you're seeing from a patient access and payer perspective. So do you feel like you've achieved the frictionless launch that you were aiming for?

Well, certainly out of the gate, we have a lot of experience with the medical exception process which is where every drug starts. We did that for 8 years with ARIKAYCE and to great success. I think our ambition here is that as we've engaged with market access players, we've tried to offer modest discounts as a part of our strategy to engage with them and work with them to ensure that their guidelines for use match things like the CHEST guidelines, which encourage the use of our drug and endorsed that when they were released in draft form in the October time frame. Going forward, we will know much more once we are into '26 about what the new policies are that are finally written by the different market access players and how those read through to patient uptake and the ease with which physicians can get a prescription filled. I want to emphasize that we have built the infrastructure in the field to support these physicians as they try to navigate the back-office authorization in a very compliant way, so the field access managers are there to help navigate through the [ Byzantine ] world of getting a prescription approved, and so far, that has gone extremely well. We have a very high number of patients who are opting into our patient support program. That is another positive. So really from every angle and every metric, this launch out of the gate is extremely strong. We've called out in our slide and certainly in our press release, some of the things that may be a little bit of a headwind as we go into '26, we don't know that they will be, but we just want to make sure that people are aware, there is a co-pay reset that hits in the first quarter of every year. It affects every drug. It could slow things a touch. But I would say the momentum behind this well outweighs the potential holdbacks.

What's your latest thinking on peak sales potential for BRINSUPRI in bronchiectasis? And what would drive either upside or downside to that?

So if you think about BRINSUPRI and what we've guided to in the past, it was prior to launch north of $5 billion in market -- in revenue. That's a very big number. it was built off of the price that we were charging, the fact that we're targeting 250,000 patients in the U.S. who are diagnosed with bronchiectasis already and have 2 or more exacerbations, if we can access that addressable population, we will get north of $5 billion in revenue in our estimation. I can tell you that, that 250,000 patients from a number of different angles is probably understated in terms of potential. We know there are 500,000 patients in the U.S. that are diagnosed with bronchiectasis. They don't all have 2 or more exacerbations but as we move through this process of learning more about the disease and as physicians learn how to diagnose these patients and treat them more effectively definition of an exacerbation and how they identify that and their patients will change. We think there's a reasonable chance that, that will increase in number and many of those patients may end up having 2 or more and therefore, be on label and definitely easily pass through the insurance process. Beyond that, the real big opportunity for this drug is the comorbid patients. Let me take a moment to drill into that because it's kind of important. COPD and asthma patients have bronchiectasis in some cases. It's not clear how widespread bronchiectasis is in that population. We know we had 15% to 20% of our patients in our Phase III study that were comorbid with those indications. But if we just take COPD for a minute, there are some 20 million patients in the U.S. who have COPD. The literature would tell you somewhere between 4% and 60% of those patients also have bronchiectasis. Now if we just take the lowest end of that range that's 800,000 patients. Remember, out of the gate, we're targeting 250,000 and that's what got us to north of $5 billion in peak sales. So you can quickly see, as you move into those broader populations of comorbid patients who are diagnosed with bronchiectasis or perhaps misdiagnosed with COPD or perhaps have both diseases. Those patients will be on label and they will represent the enormous opportunity for this drug to make a real difference in patients' lives as we get through '26 and definitely into '27 and beyond. This drug is just at the beginning of its journey, and I think physicians are going to be learning how best to apply it to the patients for their benefit, and that's going to start with an effort on their part whether they have asthma or COPD to get CT scans, look at old CT scans, see if these patients are carrying bronchiectasis, at which point they become eligible for treatment. That's what is really exciting beyond the initial launch of this drug is that there may be a massive opportunity out there for us yet to get.

And then maybe just coming off of the BiRCh results in CRC for brensocatib. Did that impact at all your expectations on the probability of success for [ BRINSU's ] CEDAR trial in HS? And what about -- did it impact your thinking about just your next-gen DPP1 potential for success in other settings like RA and IBD.

So the important thing to remember is that we're taking brensocatib, which is the BRINSUPRI drug, and we're looking at other disease states where DPP1 inhibition may be relevant in a clinical setting. CRS is 1 such indication because it affects the sinus area, it's closely related to the lung. It turns out DPP1 inhibition did not have any impact there. There was an outsized placebo effect, and we've decided that we're done with that disease state. We're also looking at HS, that's going to read out, as I mentioned before, in the second quarter. We're anxious to see those data. We think that's a long shot too. And the reason we say that is because neither of those disease states had animal models that allowed us to test and see whether or not DPP1 inhibition would be impactful. As we move into RA and IBD, those will be entering in the second half of this year with our next-gen DPP1 inhibitor. Both of those have animal models, and we have tested both BRINSUPRI and the next-gen 1033 INS DPP1 in those disease states, and we saw very good results. And in fact, we've even published some of the RA results from the BRINSUPRI work we did. So it's fundamentally different to think about CRS and HS. They're without precedent, if you will, the RA and IBD, which are much more significant market opportunities, have good animal data behind them.

Great. Well, we are out of time. So we're going to stop there. Thank you.

Thanks very much.