INSM - NASDAQ

Thank you for standing by. My name is Kayla, and I will be your conference operator today. At this time, I'd like to welcome everyone to the Insmed Third Quarter 2025 Financial Results. [Operator Instructions] I would now like to turn the call over to Bryan Dunn, Head of Investor Relations. You may begin.

Thank you, Kayla. Good day, everyone, and welcome to today's conference call to discuss Insmed's Third Quarter 2025 financial results and provide an update on our business. Before we start, please note that today's call will include forward-looking statements. These statements represent our judgment as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the projections discussed. Please refer to our filings with the Securities and Exchange Commission for more information. Also note that our call today will include blinded observations from our ongoing Phase II study of brensocatib in CRS without nasal polyps. These observations may not be representative of results once the study is completed and all data is collected and analyzed. As a result, any future interim data readouts and the final data from this study may be materially different than the observations described today. The information we will discuss on today's call is meant for the benefit of the investment community. It is not intended for promotional purposes and it is not sufficient for prescribing decisions. Today's call will feature prepared comments by Will Lewis, Chair and Chief Executive Officer; Roger Adsett, Chief Operating Officer; and Sara Bonstein, Chief Financial Officer. After their comments, they will be joined by Martina Flammer, Chief Medical Officer, for the Q&A session. I will now turn the call over to Will.

Thank you, Bryan. I'm enormously pleased to welcome all of you to Insmed's first earnings call as a company with multiple commercial products. The FDA approval of BRINSUPRI in August marked a new day for patients living with bronchiectasis and a step change in the number of patients Insmed can now serve with its medicines. Financial success is a downstream result of accomplishing the primary goal of developing first and best-in-class medicines that provide real meaningful benefits to patients. Today's update, in my view, confirms that we have a medicine in BRINSUPRI that achieves that primary goal. While we're still early in the launch and only have a few weeks of data to steer our interpretation, the positive reception we have seen to date supports our expectations of a large commercial opportunity for BRINSUPRI. So far, we have seen physicians who are motivated to prescribe it, patients who are eager to take it and payers that have been willing to reimburse it. Please bear in mind that today's results represent only 6 weeks of sales and include inventory stocking and other factors that make it difficult to discern the underlying dynamics in the early days of any launch. Given these considerations, it is challenging to glean much insight into the longer-term slope of the launch from this partial period. Our first full quarter of launch, which we anticipate reporting in early 2026, will provide a clearer look at how the launch is progressing. While we are very pleased with these results, we recognize that a lot can change as the launch progresses, and we will need to continue to execute for this launch to live up to its potential. For now, we can say that the breadth of prescribing achieved in these first 6 weeks of launch is impressive. We will continue our education efforts to build the depths to match the clear unmet medical need for this important medicine. As we have said many times, our ambition is to place BRINSUPRI in the conversation with some of the strongest respiratory launches the industry has ever seen, including DUPIXENT, Fasenra, Tezpire and Ofev. These products, on average, produced revenues in the high double-digit millions in their first 2 full quarters combined. For BRINSUPRI, that period would correspond to fourth quarter 2025 and first quarter 2026 combined. As much excitement and attention has been rightfully placed on the U.S. launch of BRINSUPRI, it is important to remember that Insmed has three late-stage or commercial programs, each with the ability to address multiple populations. In addition, beyond these programs is a significant pipeline of earlier-stage programs that have the potential to contribute catalysts over the near and medium term. Let's take a closer look at the commercial and clinical catalysts we are expecting from across our portfolio. As illustrated on this slide, Insmed's pipeline is poised to deliver far more catalysts over the next 18 months than it achieved in the previous 18-month period. On the commercial side, we have the continued U.S. launch and the expected future launches of brensocatib in the EU, U.K. and Japan, if approved. In addition, we expect continued commercial execution for ARIKAYCE's current label and the anticipated label expansion to include recently diagnosed patients with NTM MAC lung disease, assuming approval for that much broader indication. Simultaneously, we expect a host of clinical drivers in that same time frame, including data readouts from the Phase II BiRCh study in CRS without nasal polyps, the Phase III ENCORE study in recently diagnosed NTM MAC lung disease, the Phase II CEDAR study in hidradenitis suppurativa and continued progress on our Phase III TPIP program, which will include pivotal Phase III trial starts in PH-ILD, PAH, PPF and IPF. We also expect to see the first of our next generation of DPP1 enter the clinic to potentially address a range of unmet medical needs for diseases with very large populations such as rheumatoid arthritis and inflammatory bowel disease. Finally, in the next 18 months, we hope to have first looks at human data from our DMD and ALS gene therapy programs. Behind these programs is a growing and increasingly promising pipeline of first or potentially best-in-class therapies, which we expect to enter the clinic at a rate of 1 to 2 INDs per year. It is going to be a busy 2026 and 2027, and we believe we are prepared and well resourced to achieve these important milestones. Let me now take a moment to walk you through our recent regulatory and clinical progress. Let's start with brensocatib. Earlier this month, Europe's CHMP issued a positive opinion recommending the approval of brensocatib for the treatment of non-cystic fibrosis bronchiectasis in the EU. We now expect a decision from the EMA by the end of this year, setting up a potential launch in the EU in the early part of 2026. We look forward to potentially expanding brensocatib reach to include the approximately 600,000 patients with bronchiectasis in the EU. As with our prior launch of ARIKAYCE, we intend to launch BRINSUPRI in the EU at the same list price as the U.S. Elsewhere in the world, I'm pleased to report that our regulatory filing for brensocatib in the U.K. continues to progress on schedule, and our filing has now been accepted in Japan. We anticipate each of these filings could open up additional growth opportunities with potential approvals and launches in the U.K. in the first half and Japan in the second half of 2026. Moving now to our clinical progress. The BiRCh trial of brensocatib in patients with CRS without nasal polyps, continues to progress on schedule for completion by the end of 2025. Depending on the time it takes to thoroughly clean and lock the data, we expect to announce the top line results for the study no later than the early part of January. As you know, our practice is to clearly define what we believe to be the bar for success ahead of any top line readout. Currently, the only approved treatment option for CRS without nasal polyps is a nasal steroid device that showed a 0.7 placebo-adjusted improvement for the lowest approved dose on the same scale being used as the primary endpoint in BiRCh. As a reminder, brensocatib is being studied on top of a stable course of nasal steroids, so any treatment effect shown would be additive to the standard of care. As such, we would consider a placebo-adjusted 0.7 treatment benefit, a clear win, matching what was adequate for FDA approval in the past. BiRCh is 80% powered to show a 0.97 placebo-adjusted treatment effect, which is a larger treatment effect than what we believe would be adequate for approval. If the study were to demonstrate that level of effect for brensocatib, that would represent a home-run scenario. Please note that BiRCh powering, I just mentioned, is based on an alpha level of 0.1. Given that this is the first study ever conducted for this mechanism in this patient population, the goal is to gather strong directional information as quickly as possible to inform our potential pursuit and design of a future Phase III program in CRS without nasal polyps. And alpha of 0.1 is a stringent bar for a Phase II that is designed to detect early evidence of efficacy. This level of powering means that a successful outcome could generate a p-value for the primary endpoint that is higher than 0.05, presuming the magnitude of the treatment effect is meaningful, and we see consistency of improvement across multiple efficacy end points. With nearly 30 million patients diagnosed with CRS without nasal polyps in the U.S., we will be interested in selling any subpopulations in the trial where the treatment appears to have the greatest impact. While we have no reason to believe at this time that only a subpopulation will respond, even a subset of these patients could represent a very large additional patient population for us to serve should a future Phase III program demonstrate adequate safety and efficacy results. We continue to observe promising blended blinded data from the study with the improvement across all patients who have completed the study exceeding a 2-point change from baseline. We look forward to sharing the top line results with you after the study is completed. Now let me provide an update on our CEDAR trial in hidradenitis suppurativa. I'm very excited to report that due to strong patient interest, the CEDAR trial is now fully enrolled. This timing is well ahead of our internal projections and exceeded the study's 204 patient enrollment target with 214 total participants randomized. In fact, the trial completed enrollment so quickly that the final readout is now expected only weeks after our planned interim futility analysis of the first 100 patients. For this reason, we have decided to forgo the interim futility analysis, which was planned for the first quarter of 2026 and instead plan to report CEDAR's top line readout, including data from all 214 patients in the first half of 2026. The primary endpoint in the study is the percentage reduction in abscess and nodule count, or AN count from baseline. AN count differs slightly from the commonly used high score endpoint because there is no requirement to show a stabilization or decrease in draining tunnels. While we believe that brensocatib is likely to have a positive impact on tunnels, we think that impact may take longer to manifest itself, which is why we chose and count as the primary endpoint for this 16-week study. Let me also provide you with a clear definition of what we would consider a win for this top line readout. We view an approximately 20% placebo-adjusted reduction in AN count for either dose to be the bar for success in this trial. We believe that this magnitude of effect would be viewed as clinically meaningful and would encourage us to advance the program into Phase III. Our CEDAR trial is 95% powered to show a 40% placebo-adjusted reduction in AN count. We would consider this outcome to be a home run for this data readout. Like the BiRCh trial, CEDAR is powered at an alpha of 0.1 so they can more quickly inform the design of a Phase III program, if warranted. As we've said before, HS is a challenging disease to treat successfully with recent clinical trial results from other programs underscoring this sentiment. However, we remain hopeful that our novel approach will yield a positive outcome for moderate to severe HS patients that we believe would welcome a safe and effective oral treatment option. Turning now to TPIP. We continue to receive consistently positive feedback from the treating community for our Phase II data in patients with PAH. Last month, we presented the full results at the European Respiratory Society's meeting in Amsterdam, and we're pleased by the reception it received. We are now focused on conducting an expansive registrational TPIP program, which will include Phase III studies in PH-ILD, PAH, PPF and IPF. The first of these studies is called PALM-ILD, a 344 patient trial in PH-ILD, which remains on track to open sites before the end of the year. This trial will measure the change in 6-minute walk distance at 24 weeks of treatment as the primary endpoint, and we'll take those measurements 1 to 3 hours post-administration of the most recent dose. Measuring the primary endpoint 1 to 3 hours post-dose is the change from the approach we took in Phase II, where all efficacy measures were taken approximately 24 hours after the most recent dose. We designed the prior trials that way, so we could definitively answer the question of whether our once-daily formulation provide a benefit throughout the entire dosing interval. Now that we have clearly established that benefit, we have chosen to design our pivotal trials more consistently with the trials of other approved prostanoid treatments, which took their measurements at peak exposures. Importantly, treatment effect on 6-minute walk distance at crop exposure or approximately 24 hours after the most recent dose will also be captured as a secondary endpoint. I'm pleased to share that the data monitoring committee for TPIP convened earlier this month and reviewed unblinded data from Phase II programs and the open-label extension studies for PAH and PH-ILD. Not only did they recommend that the OLE studies continue unmodified, but they also strongly encouraged us to move into Phase III based on their review of the data. Additionally, we recently completed our end of Phase II meeting with the FDA and align with the agency on the data package that will be required to support a regulatory submission for TPIP and PAH. Based on the outcome of that meeting, we plan to conduct a single Phase III study in patients with PAH with the primary endpoint of 6-minute walk measured at an alpha level of 0.05. If successful and as discussed at the end of Phase II meeting, we will submit an NDA that will include the Phase III data, along with our Phase II trial data as confirmatory evidence. We expect to initiate the single Phase III trial of TPIP in patients with PAH in the early part of 2026. We have also begun ramping up our manufacturing of TPIP to adequately source the additional supply needs of the Phase III studies in PPF and IPS. Given those supply requirements and the need to align with the FDA on trial design, we anticipate initiating the registrational trials in PPF and IPF as soon as possible, but likely in the second half of 2026. When you add potential Phase III starts for brensocatib in CRS without nasal polyps and HS pending positive Phase II results we may be kicking off as many as six new Phase III programs requiring up to almost a dozen Phase III clinical trials in just the next 12 months alone. Now let's touch on ARIKAYCE. Even with an enormous amount of activity happening at the company, ARIKAYCE has continued to perform. Not only did ARIKAYCE posted another strong quarter of year-over-year revenue growth, but the Phase III ENCORE trial continues to progress on schedule towards its readout. If successful, ENCORE could expand the label for ARIKAYCE to include all patients with the MAC lung infection, increasing the addressable patient population in the U.S. from around 15,000 today to more than 100,000. The number of patients who could be served by this medicine in Japan would be even larger, resulting in more than 25 million patients worldwide. As a result, we believe success in ENCORE could lead to ARIKAYCE becoming a blockbuster product. Recall that in our first Phase III study in this patient population, ARISE, patients treated with ARIKAYCE showed faster, greater and more durable effects on culture conversion compared to the active control. In fact, about 80% of patients in the ARIKAYCE arm achieved and maintained a negative sputum culture at month 7, which was 1 month off treatment compared to 47% of patients in the control arm. These results emphasize the benefits of treating earlier with ARIKAYCE, given that in our Phase III refractory trial convert about 1/3 of patients converted by month 6. And on a much more challenging endpoint of durable culture conversion after 3 months off treatment, 16% of patients in the ARIKAYCE arm were able to show durable culture conversion compared to 0 of the patients in the control arm. ARISE also validated a patient-reported outcome tool while showing encouraging directional benefits on that measure. The ENCORE trial was recruited at the same time and for many of the same sites as the ARISE trial and the patient demographics look very similar between the studies. So we remain cautiously optimistic that the trial results will also be similarly positive. As a reminder, a primary endpoint of culture conversion will be used in Japan, while the PRO will be the primary endpoint in the U.S. We look forward to turning over this data card in the first half of 2026. Moving on to our early-stage pipeline. The Phase I ASCEND trial of our gene therapy for DMD has completed dosing of its first cohort of three patients. While early, no concerning safety signals have been observed to date, which is encouraging. We believe this may reflect the benefit of our intrathecal delivery approach, which was designed to avoid passing through the liver prior to getting to the skeletal muscle and cardiac tissues where it is needed. We look forward to expanding the ASCEND trial to include a cohort of younger patients and a cohort testing a higher dose in patients of the same age as the first group. Our second gene therapy program for the treatment of patients with ALS is also making strong progress. The IND for the treatment recently was cleared to move forward into the clinic, so we are now preparing for the start of a Phase I trial. Like our DMD therapy, this treatment will be administered intrathecally. We are particularly excited for this program because we will be studying it in both SOD1 and the much larger population of sporadic patients based on strong data generated preclinically for models for both populations. In addition to our gene therapies, we continue to advance our next-generation DPP1 candidates were the first expected to enter the clinic in 2026. These novel next-gen molecules will be used to pursue indications in very large patient populations where there still exists significant unmet need. We'll begin by introducing INS1033 in simultaneous studies in rheumatoid arthritis and inflammatory bowel disease, followed by other novel DPP1 in COPD and possibly many other indications. We look forward to sharing more details as these programs progress. Before I pass the call over to my colleagues, I want to reiterate that we are just at the start of this wave of commercial and clinical readouts trial initiations and research translation into the clinic. As gratified as we are by our recent achievements, we are even more enthusiastic about Insmed's future. Over the next 18 months, we will be focused on executing on the many opportunities we have just reviewed. This is a very exciting time for Insmed as the many years of planning are finally yielding the results for which we had all hoped. This presents us with the opportunity to further realize our mission of bringing these promising first or best-in-class medicines to patients with serious diseases. Finally, I must mention that for the fifth year in a row, we were awarded the distinction of the #1 ranking on Science Magazine's Top Employers list. The only other organization to achieve this in the 20-year history of the survey was Genentech, which puts us in rare company. We are extremely proud of this accomplishment, which punctuates the preservation and success of our culture despite our rapid growth. Let me now turn the call over to Roger, who will walk us through the recent launch performance of BRINSUPRI in the U.S. and the third quarter's commercial performance of ARIKAYCE.

Thank you, Will. I'm delighted to provide some detail on BRINSUPRI's performance. In its first partial quarter of launch, BRINSUPRI achieved $28 million in net sales. We are very pleased by the strength of BRINSUPRI launch in these early days and the reception it has received from the treating and patient communities. As of the end of September, approximately 2,550 new patients had started treatment with BRINSUPRI and about 1,700 physicians had written at least one script including physicians in academic centers as well as many in the community setting. Most of these prescribers through September have written just one or two scripts in total. This pattern is consistent with the common practice of trying out a new medicine by prescribing it to a small number of more severe patients and then waiting to see how those patients do on the treatment before expanding the medicine's usage. Remember that it can take 4 to 6 weeks for BRINSUPRI to reach its full pharmacodynamic effect and potentially much longer than that for patients and physicians to notice this effects. So those physicians who are testing their medicine in a few patients may need time to determine whether they will expand their prescribing habits. Overall, I would describe the early days of the launch is seeing very broad prescribing in terms of the number of physicians. If we also see deeper prescribing patterns where physicians move to the adoption phase and begin prescribing BRINSUPRI to larger percentages of the patients both at centers of excellence and in the community, we should see the launch accelerate. But of course, it's too early to know if or when that will happen. This is why we feel BRINSUPRI's first full quarter Q4 and will provide us far greater insight. The medicine specific inclusion in electronic medical records for selection of prescribing and prior authorization criteria at insurance companies getting more standardized should together enable the wide range of physicians an easier path for prescribing. This is particularly true at the centers of excellence where large numbers of patients are treated and back office logistics can limit the number of new prescriptions processed each week. None of this comes as a surprise to us, and we believe we have extensive compliance support systems to assist where we can. Additionally, just last week, we saw an update on U.S. guidelines for the treatment of patients with non-CF bronchiectasis at the CHEST conference in Chicago. We are encouraged that BRINSUPRI has been included in the preliminary CHEST guidelines, and we look forward to the forthcoming publication. We hope that these guidelines, once published, will help physicians to make treatment decisions that are best for their patients while providing supportive guidance of best medical practice to payers in setting their prior authorization criteria. On the market access side, the early days of the launch have also been encouraging. Due to BRINSUPRI being the only approved therapy for this condition, broad patient access has been achieved from day 1 as we expected. Even without formal contracts in place, the vast majority of prescriptions have been approved for coverage, both on the Medicare and the commercial side of the business. However, there is still plenty of work to be done. We continue to engage with payers in both the national and regional level to establish simple and convenient prior authorization and reauthorization requirements that can allow access to BRINSUPRI that is as frictionless as possible. These discussions are still ongoing, and we will need more time before we have a good sense as to where contracting and access requirements will shake out. As it is common to see some slowdown, once criteria are firmly established and enforced it is important to interpret this quarter's relative ease of access within that context. When assessing the revenue and patient figures achieved this quarter, it's important to recognize that these sales numbers benefited from a couple of factors. Firstly, based on our prior experience with ARIKAYCE, we had said it could take up to a month from the time of FDA approval for the first sales to be recorded. In the case of BRINSUPRI, we accomplish this in less than half that time, which is a testament to the readiness of our commercial and technical operations teams. This meant that the third quarter reflected about 6 weeks of revenue and patient starts rather than the 2 or 3 weeks we have previously expected. Secondly, these results reflect the impact of necessary inventory stock in the channel, which accounted for approximately 40% of BRINSUPRI revenue this quarter. Importantly, our specialty pharmacies can get BRINSUPRI within 24 hours of placing an order and aim to hold only a limited number of weeks of supply on hand at any given time. As a result, we do not anticipate a significant contribution from inventory stocking in the fourth quarter. In summary, the early days of the launch have left us feeling excited about the future possibilities for this new medicine. There is plenty of work ahead to ensure that in super is successful in the way that we hope and believe it can be. We are wholly committed to working tirelessly toward that goal. Now let me provide some commentary on ARIKAYCE's performance in the third quarter. We continue to be extremely pleased by the strength of the brand even as we approach the end of its seventh year on the market. This quarter, ARIKAYCE once again posted its largest quarter of revenue ever up 22% compared to the same quarter last year. This result was driven by double-digit growth in each of our geographic regions. In the U.S., despite the significant attention that has been placed on BRINSUPRI's launch, ARIKAYCE grew 11% compared to last year, demonstrating our commercial team's ability to execute with excellence on multiple products at once. Outside the U.S., we saw a continuation of the impressive growth we've seen for several quarters now. With our international business comprised of Japan and Europe, setting a new all-time high and growing more than 50% compared to the same quarter last year. We are proud of the dedicated work of our commercial teams across the globe to bring this medicine to ever more patients who need it. So with that, let me turn the call over to Sara.

Thank you, Roger, and good morning, everyone. On the heels of Rogers commercial review of our two approved products. I am pleased to report that we are raising our 2025 full year global ARIKAYCE net revenue guidance to $420 million to $430 million, up from a range of $405 million to $425 million previously. As a reminder, this guidance range is specific to ARIKAYCE only. The updated guidance range demonstrates the team's ability to execute across multiple products as well as reflects the excellent execution of our commercial teams around the globe. Now representing a 15% to 18% increase over full year 2024 ARIKAYCE revenues. Now let me spend a moment on our cash position. At approximately $1.7 billion in cash, cash equivalents and marketable securities as of the end of the quarter. I believe Insmed continues to be well capitalized. Excluding cash received related to option exercises, our underlying cash burn for the quarter was relatively consistent with the underlying burn levels that we have seen for the past several quarters. Keep in mind that only a portion of the BRINSUPRI revenue we recognized this quarter have been received in cash as of September 30. So our cash burn does not yet reflect that full benefit. As we have said before, we expect both revenue and spending to continue to increase as we fully resource and support BRINSUPRI's launch as well as the other portfolio programs expected to initiate in the near term. We are pleased to be entering this exciting period in a strong cash position. Moving now to the other relevant financial metrics for the third quarter, which are shown here on the slide. Cost of product revenues in the third quarter of 2025 was $29.4 million or 20.6% of revenues, which is lower on a percentage basis than our historical performance, reflecting the positive contribution of BRINSUPRI to the company's gross margin profile. Additionally, as expected, research and development and SG&A expenses increased this quarter compared to the prior year period. due to the necessary investment made to support the U.S. launch of BRINSUPRI and to continue to fund our growing pipeline. In closing, we have so much to look forward to. The remarkable string of clinical and commercial successes we have experienced in the past 18 months have provided us with new opportunities to serve patients in need, whether that be with the launch of a new product to hopefully change the lives of patients or the initiation of new Phase III programs, which can provide hope to patients waiting for new treatment options. Insmed remains in a uniquely strong financial position from which to execute on each of these opportunities. We would now like to open the call to questions. Operator, may we take the first question, please?

[Operator Instructions] Your first question comes from the line of Jessica Fye with JPMorgan.

Congrats on the launch. I was curious if you could talk a little bit about some of just the early feedback you're hearing from the field about the physician experience with BRINSUPRI? Both in terms of how they feel like their patients are doing kind of speaking to that phenomenon where they might try it in a few first and then go from there, but also their experience with the reimbursement process.

Yes. So I'll just make a quick general comment and then turn it over to Roger. I think the word from the field net-net is positive. We've attended both European Respiratory Society, but more relevantly, CHEST recently, where we had the opportunity to interact with a lot of physicians. And I would say to a person that I encountered there's nothing but enthusiasm out there for this, and its potential. And I've heard anecdotes that are supportive of the statements that Roger made related to market access. But Roger, I wonder any other thoughts you might want to add?

Yes. Thanks, Will. No, I think the sentiment is, as we described, quite positive. I think that the broad prescribing base that we've seen so far reflects some enthusiasm for these physicians to at least try with their more severe patients who are in the office and need that attention. And so as we talked about that, they're in that trial phase and hopefully, we'll move into an adoption phase. And it's still early days, right? So I think as we talked about the pharmacodynamic effect of BRINSUPRI and the way that it works, it could take a little while for that response, and we're hoping that the positive feedback that comes from patients to the physicians, once they feel that impact, hopefully, less coughing, et cetera, will encourage additional prescribing. On the market access side, I think what we're hearing is actually some positive sentiment there. It's been quite straightforward to get for most patients to get this through from a payer perspective. It's not uncommon for that to happen in the early days of launch as we talked about. The payers haven't yet finalized their criteria. Medicare has to review this within a certain time period. And so we expect that patients are experiencing that a little bit of a honeymoon period from the first approvals. As payers start to finalize their criteria and as they start to enforce that criteria, while the physicians and their back office staff adjusted that, and we can help them with what that criteria looks like in a compliant manner. It may slow down just a little bit. But we expect that given that profile is the only approved product in the category into the disease state that we can achieve our goal of having frictionless access for patients and physicians going forward. And that's what we continue to work towards.

And let me just say, I want everyone to take away from this call. We feel great about where we are with the launch, but we're just incredibly cautious because we only have 6 weeks of data to work off of. And it's very difficult to extrapolate that because there are lots of puts and takes in these data in this short period of time. We really feel like we need the fourth quarter to know what the directions are that are being established in both physician treatment across the spectrum of community to centers of excellence. So sort of encouraging, but let's hold off on reading too much into this until we've got a full quarter under our belt.

And your next question comes from the line of Ritu Baral with Cowen.

Roger, well, you guys have been really good at sort of setting thresholds and bars for success across data, et cetera. What threshold do you see for that payer coverage that we should keep in mind going forward? Are you going to set a bogey for us going forward and they covered lives or time to fill. We've had great feedback on so far, but to your point of early coverage. Also, what criteria are you aiming for, for that final threshold for prior ops and the reauthorizations, Will, that you mentioned?

I'll make the general comment that our objectives with market access are to accomplish what we described as a frictionless launch. What that looks like is in the practical setting, is that the criteria for approval are clear and well established and are not overly burdensome to physicians. These are patients who have two or more exacerbations and have a confirmed diagnosis of bronchiectasis. And we think it's appropriate for physicians to be able to attest to that without necessarily providing all of the backup documentation for that kind of a diagnosis. If it's required to do all of that, then so be it. But we would prefer that, that not be the case. And we're willing to do some modest discounting out of the gate to try to accomplish that set of criteria and to make it easy for physicians and back office and also for the process of reauthorization. And I think so far, we're making very good progress on that front. I don't know, Roger, if you want to add anything to that?

I think you captured it well, Will. I think the only thing I would add is that as we look to get this criteria established and that's really our goal, and we've been as you know, pre-approval, we've been engaging with payers representing about 90% of our targeted lives. And we -- at both the national and the regional level. And what our goal is, as Will described it, to get -- to make this as easy as possible for patients to get the product and easy on the back office of physicians as they're tax with all the usual paperwork that they have to go through across a variety of medicines. Our goal is not necessarily a formulary addition. So we don't really have targets for that. Our goal is to get that criteria clear and as easy as possible for the physicians, as Will described, and we continue to work towards that.

And your next question comes from the line of Joseph Schwartz with Leerink Partners.

Hats off to such strong execution so far. So I guess how frictionless has the launch been to date in your view based on the amount of documentation physicians have had to provide to payers? Do you have any early reads on how this dynamic has been playing out so far?

Well, I think what we would say is that, so far, so good. There is actually a mix of what has been required in terms of the medical exception process. And in some cases, it has been necessary for physicians to provide both the documentation of CT scan with a positive diagnosis and documentation of the exacerbations. And in those cases, what we've heard from physicians is it's not that bad or onerous to do that. We're just trying to make it easier for them through some potential modest discounting there's not a ton of room to be able to do that. I mean if we look at benchmarks for what Sara has commented on in terms of -- it's not guidance, but it's what you would see in early launch of a product of this profile fully half of that discount is attributed to our contribution needed under IRA. So it doesn't leave a huge amount to offer in terms of discount, but we're doing what we can to try to make this process easier for the physicians in the back office, as Roger described it. And I think, so far, so good. But time will tell. And all I would say is that whether we need to provide all of that documentation or none of it that will be something we determine in the coming months. But either way, we're going to be able to ensure that we can support compliantly the efforts to gain access to this medicine for patients. And I think this is one point that's really in our favor. This is a great medicine. This has a low AE profile from its Phase III data as published in the New England Journal of Medicine. Its efficacy is clear. It's across multiple end points. highly statistically significant. And this is easy to take with a low burden on patients. So it really suggests itself both by its ease of use and by its potential for these patients in terms of them getting better. So for all those reasons, I think market access should continue to be something that we're able to navigate.

And your next question comes from the line of Jason

Congrats on the great progress. Will, I was hoping you could provide some additional color on some of the softer dynamics about the patient journey for BRINSUPRI's launch. How has the DTC impacted awareness? Are you seeing more sort of interest from the patient side of things, more from the prescriber side of things? As they inquire about treatment for their disease.

Thanks for the question. Look, it's always hard to discern the qualitative side of the launch from both the physician and patient side. What I can tell you is that there is clear enthusiasm from the patient side of the equation. One of the most gratifying things to us when we got a product in the channel and patients were getting their first prescriptions filled is that they were posting images of themselves holding the bottle on social media. That's about as good as it gets in terms of patients' enthusiasm for the arrival of a medicine that can make a difference in their lives, and that is what we're all about at Insmed. I think the physicians are also similarly well aware of the arrival of the medicine by virtue of all the excellent work that our commercial team has done. But the practical application of the awareness of the medicine to a patient population is where the rubber meets the road, and it's too early in these early weeks to discern what that pattern of behavior is going to look like. And I think that's what Roger was commenting on in his prepared statements in describing trial use of the medicine and then a broader adoption phase and depth of prescribing. And that's what we're really going to be looking for in Q4 and indeed in 2026 to ensure that this launch continues to go the way we hope it does.

And your next question comes from the line of Andrea Newkirk with Goldman Sachs.

Just as you look to launch in Europe in early next year, what types of investments are needed to prepare for commercialization, maybe particularly with respect to your sales force infrastructure. And then, Sara, I was just wondering if you might be willing to share what your gross to net adjustment looked like for BRINSUPRI in the quarter?

Sure. I think thematically, our strategy in Europe is to sort of ensure that the reimbursement ends up the way we need it. to end up before we start doing significant additional investments. We've done some in preparation, obviously. And in Japan, we have expanded our sales force already by virtue of the opportunities for ARIKAYCE, which has proven to be a very wise decision, and I think prepares us for the launch of BRINSUPRI if and when that receives approval, which we expect in the second half of next year. At that time, we would also consider expanding even more in Japan. But I don't know, Sara, perhaps you want to comment in greater detail on that on the margin question.

Sure. Happy to. Thanks, Andrea, for the question. So on the margin question, we're not providing quarter-to-quarter BRINSUPRI gross to net. What I can say, obviously, most folks are where off the bat of any launch, you see a little bit of flexibility lumpiness in your gross to net, while not formal guidance, as Will mentioned earlier, we did provide sort of those analogs of 25% to 35% at launch, when you take in the half of that is the IRA impact and then sort of normal standard contracting for an at-launch product, and we remain to say those are still reasonable analogs. As you're thinking about investment, as Will said, will be a little bit more cautious in Europe as we're thinking through sort of the reimbursement piece there.

And your next question comes from the line of Vamil Divan with Guggenheim Securities.

Great progress. Obviously with BRINSUPRI, I wanted to actually ask about TPIP, which we're also very excited about. I'm curious -- at it all is on the Phase III design. As you're thinking about it for the IPF and PPF trials. And specifically, we've been getting questions from [indiscernible] your potential -- new potentially need to overcome orphan drug exclusivity in that space, given the progress United Therapeutics is showing. I'm just curious if maybe you can comment on how you would need to design that program to ensure your ability to launch it?

Sure. Well, as you are well aware, there are a number of ways to overcome the orphan designation, which would be over in a second. But I think it's still early for IPF and PPF. We are ramping up our production. We certainly intend to go into Phase III, and it is our strong belief that it will not be a too high a hurdle for us to overcome the orphan designation. But I wonder, Martina, if you want to just walk in a little bit more detail where we are in our thoughts about that.

Yes. So on IPF and PPF, I mean, as you know, TETON was a clear win for patients. And we will take the TETON study and what we've learned from that in how we -- how it informs our design. What we've taken away is also -- and you've seen that in the TETON study that the dosing, it has a big impact. And I think our ability to dose and titrate the dose up to a need optimally for the patient. So it's an individual dosing exercise gives us certainly an advantage. And otherwise, I think you look at what TETON has shown that gives you a very good road map of how we think about IPF and PPF. And when you -- especially when you think about orphan, I know that was one of your questions, if you are intending to be better than on currently existing orphan designation, exclusivity, you have the ability to show you superiority in terms of efficacy, safety or an impact on patient care, one or more of them. We have the opportunity to do that from an efficacy perspective, you've seen our strong results in PAH from a trial impact perspective, but also how we are able to provide maybe a once-daily dosing, this is not only important from a tolerability perspective, but it is also an impact on how patients are able to actually stay on treatment and to increase the dose on the treatment. So both on efficacy, safety and potential impact on patient care are opportunities for us to show how good TPIP can be in this indication.

And your next question comes from the line of Gavin Clark-Gartner with Evercore ISI.

Congrats on a really fantastic quarter. I just wanted to ask a couple of questions on BiRCh really quickly. What's your expectation for the control arm TSS reduction from baseline? And then just on the baseline characteristics of the trial, what's the baseline TSS score? And how many patients are above or below 300 for the eosinophil fill cutoff?

Martina, do you want to take that?

Yes. So with regards to what our placebo background rate or placebo assumptions are. So we get some indication from other trials that have been done, the reopen trial, which was on with the Optinose exhale device, which is based on a steroid treatment then also we're looking at trials like the ORION trial that was done with DUPIXENT. But I do want to keep in mind for all of you that we are conducting our BiRCh trial on top of a steroid. So patients are already 4 weeks on a stable steroid therapy, and patients come into the trial with baseline score of the sTSS or the final total symptom score of 5 or above. And we're looking at that at screening as well as baseline sort of randomization. We look also at the last 7 days of this score. So we are taking the 7-day average of the sTSS and look for above 5. Just so you know, the most severe is 9. And your second question was about what do we see with eosinophils at baseline. So we enrolled both for the low and above 300 eosinophils, and we're looking what will be -- irregardless of where patients are our ITT analysis will be based on the entire population. So both for patients above and below 300 will be the assessment for the primary endpoint.

And your next question comes from the line of Clara Dong with Jefferies.

Congrats on the great quarter. Really great to see BRINSUPRI your launch of a real good start. So just for BRINSUPRI, are you anticipating any seasonality effect for the patient flow in fourth quarter and beyond such as weather-related factors or availability of diagnostic procedures like CT scans during the holiday season?

Roger or Martina, do you want to take that?

So maybe I can just comment on generally, seasonality is always something that you see in it could be a trigger of exacerbations. We've not seen really a significant limitation on patients being able to access CT scans. I mean, over the holidays, patients usually don't seek out unless they are in an acute situation, their physicians, but it has not been a limitation as far as we know at this point.

And maybe I can just share some color from -- as we think about it from a commercial perspective, I think obviously, with the holidays, sometimes you see a little slowdown from physicians seeing patients. But I think probably what we're watching more closely is as we go into 2026 and we think about the reset from a Medicare perspective and the co-pays that will be required for the deductibles, we'll keep a close eye on that as well as any kind of reauthorization criteria. So that's -- again, I don't know what's going to happen there, but we'll continue to monitor that and see what impact we have going forward.

And your next question comes from the line of Ash Verma with UBS.

Congrats on this strong quarter. So just on the BiRCh study, do you have this data in-house already just realizing that the primary completion was also August and I think you mentioned that it will come in early Jan, depending on how much time it takes to clean and process. But as of today, do you have this in-house?

So I know that we're moving as quickly as we can to process the data and lock the database and do all the necessary cleaning in order to accomplish that. I don't know, Martina, if you can give any more color on it than that. Certainly, our time line is as soon as we can get it, but it may just end up making more sense for this to be coordinated in the early part of January, versus trying to blow up people's holidays and have it put out between something like Christmas and New Year's, which I don't think would serve anyone's interest. But Martina, any commentary?

Yes. So for BiRCh, like many of our studies, we tend to get data in-house almost in real time. The last patients are still just completing the study. So there is still some data that is coming in, but the vast majority is in the cleaning process. And as you know, we've done this also in ASPEN or also in TPIP. When we look at the database close when we look at how we clean the data, we do this from a perspective so that it meets the highest regulatory standards, and it will always then put us in a position to also demonstrate that these are supporting evidence. And that's why we're taking our time to ensure that we have the highest regulatory standards with database lock as well as with the cleaning of the data.

And your next question comes from the line of Ben Burnett with Wells Fargo.

And congrats on the quarter so far. Just on BRINSUPRI, I appreciate that it sounds like some of the early use of this has been with severe patients. some of the early adopters. But I guess what's been like the feedback among physicians and sort of the appetite among physicians to use this in maybe more moderate patients or even patients with only one recent sort of exacerbation?

Well, I think it's still early days with the medicine. We can start with the parameters that we know, beginning with the label, which is, as you know, quite broad, I think from our point of view, we've heard from physicians, and we try to stay in close dialogue with them that they feel that the most obvious patient that's a candidate for this would map the entry criteria of the ASPEN study. So two or more exacerbations in the last 12 months. And that's really where their early efforts have been focused and I would call that a moderate to severe patient profile. And I think that's certainly the sweet spot for the medicine out of the gate. We'll learn more about other populations that may be appropriate. Those could include patients who are a little bit more moderate than what was described. But I think just to work clear, our focus with the market access world has been on two or more exacerbations to match the entry criteria of our Phase III program. We'll see what physicians want and where they want to take it. I also think that it's interesting for us to consider as time goes on, the opportunity to get to the COPD and asthma comorbid patients who may either have been misdiagnosed and have bronchiectasis or are comorbid with those indications. Remembering that in Phase III in our ASPEN study, there were about 15% to 20% of the patients who are actually comorbid with either asthma or COPD and bronchiectasis and they were all responsive to treatment. So there's a big opportunity out there for sure. One step at a time. And as physicians learn their way with this medicine and see the patient response to it, I think that will shape this as much as anything.

And your next question comes from the line of Leonid Timashev with RBC Capital Markets.

I wanted to ask on CRS. And you guys mentioned subgroups that you may be looking at. I just wonder if you could speak a little bit more about which subgroups you might be considering diving deeper into beyond maybe just being the eosinophil counts and whether that's driven by your thoughts around the commercial opportunity given that CRS is a much larger population than pharmacy ectasis or whether it's driven by trying to maximize clinical benefit in some of these populations?

Yes, I think the short answer to that question is we don't know yet. There isn't a lot of background in CRS without nasal polyps generally in terms of subsegmenting the population. The overall population is in excess of 30 million patients in the U.S. And this study is designed to look for signals and directional groups that might benefit from it. It could be that we see benefit as we did with ASPEN across all etiologies that gave rise to the bronchiectasis. In this case, for CRS without nasal polyps, there may be all patients benefit. It may be just a subpopulation. We don't really have any theories about which group might be responsive in that way. And I want to be really clear, we're not suggesting based on anything we've seen that it will only be subpopulations, we just want to highlight that if it is a subpopulation still could be a very substantial opportunity given the enormity of patients with this condition. So we're going to follow the science. We're going to see what the data shows us, and we'll certainly share that -- those conclusions as we move forward. Eosinophil count is an interesting one because we theorize that, that could be relevant. But once we looked at the ASPEN data, it became clear that it was not going to be controlling on the performance of the medicine in these patient populations. And so we consolidated that stratification we'll still be examining it in the study, but it's no longer in our judgment required out of the gate to separate patient populations with regard to the primary endpoint. So it's an example of the kind of learning we're going to do as we go. And as I said, we'll follow the science and see where the medicine is of greatest benefit, and that's where you can expect us to concentrate our efforts should the data be strong enough to take us into Phase III.

And your next question comes from the line of Olivia Brayer with Cantor Fitzgerald.

On brenso's EU list price, can you just comment on the decision to keep that the same in Europe versus the U.S.? What's been the feedback from payers on the price point? And is there anything that you can tell us at this point just around how gross to net discounts in Europe might look versus those in the U.S.? And then just quickly on the prescriber mix in the U.S., what proportion of those initial 1,700 writers or from an academic versus community settings? And how does that compare to the overall mix in the broader bronchiectasis market?

So thanks for the questions. The prescriber breadth, I think, is a point that we've called out as something of strength because it indicates that we're getting access to -- with that number of prescribers obviously are gaining access to both centers of excellence, which we fully expected, but also much more broadly in the community, which was a deliberate focus of our calling effort. So we're excited to see that breadth of prescribing. We now need to see those physicians and more like them go deeper with multiple prescriptions written for patients and that will become clear in the coming quarters. Whether or not that's happening in which way. But there's nothing we can discern at this moment other than the engagement from physicians has been very broad. With regard to the EU list price, it's our practice as we did with ARIKAYCE to match the list price in the U.S. with Europe and Japan. They all are often negotiations that take place in the gross to net discussions with payers that can impact the ultimate net price paid quite substantially in some cases, but we have less control over that. What we want to make clear is that we think this medicine has value for patients. We think the price we've selected is the appropriate one, and we look forward to the discussions with the different reimbursement authorities to determine what the ultimate net price will be.

And your next question comes from the line of Stephen Willey with Stifel.

Congrats on execution. Just a TPIP question. So should we assume that the single Phase III PAH trial that you reached alignment on with FDA will be looking at a patient population that's similar to the Phase II? And then also curious if there was any feedback around kind of what a label might be able to claim and how you may be thinking about additional studies to potentially support utilization of TPIP across a broader spectrum of functional class patients?

Appreciate the question. I'll ask Martina to comment in a minute. What I would just say is that our perspective on this medicine because of our ability to titrate higher, because of our ability to deliver once a day and its formulation is a dry powder we have really the high ground with regard to patient potential impact and convenience, and that is a very important driver in this population. But what is most remarkable to me was that we were able to see a 35.5% PVR reduction, which, to the best of our knowledge, the very best score ever achieved for any medicine in any clinical study in PAH. We keep looking for something better. We haven't seen it. Sotatercept, I think, came in around 33 or 35, so we edged that out, and it's a different kind of medicine, obviously, and it's not an apples-to-apples comparison, but using that metric as an anchor point, we can see that TPIP really has quite a bit to offer these patients. Where we go from here will be determined by the strength of the Phase III data for sure in terms of label. But Martina, perhaps over to you for some commentary on our TPIP drug.

Yes. So for PAH, as you know, it is our practice that we try to keep our Phase III studies consistent with what we've seen in our Phase II studies. And that is what we are looking to do also in this particular study. What we have now seen in between this in the OLE program that we were able to titrate patients up to a higher dose. In the Phase II study, we did not have the dose up to 1,280 micrograms. And in the Phase III study, the plan is to allow titration up to 1,280 the maximum tolerated dose on the individual level. And that is something which will likely be a change, but we're doing this also based on the experience and what we have seen from both the safety side in the open-label extension study already. But otherwise, you can expect some consistency over from the Phase II study.

Your next question comes from the line of Matthew Phipps with William Blair.

Congrats on all the infection at pipeline and commercially. Do you have any sense yet on what dose is getting preference for prescription of BRINSUPRI? Is the 25 mg potential loan function benefit resonating with physicians to go with that and may help some of the kind of feedback loop you talked about earlier?

Roger, do you want to take that?

Yes, sure. So right now, we're seeing the majority of the prescriptions coming in for the 25 milligrams, but we are seeing that some of the physicians are choosing to start with a 10. So we do think that the lung function is resonating, particularly with the thought leader community. But as it's not atypical with new medicines, some physicians start to choose to start low, and they may be increasing their dose as they go forward and move into that adoption phase as they get more experience with the medicine.

And your next question comes from Maxwell Skor with Morgan Stanley.

Congratulations on a very strong quarter. So I appreciate that we're still early in the launch, but how would you characterize BRINSUPRI's performance to date relative to the launch analogs you provided? And how is this stacking up to expectations for the next 2 full quarters and then the following 4 quarters, I believe that you've provided some guidance towards?

Yes. So to be clear, we haven't provided formal guidance of any kind. We've only tried to put out benchmarks for what good looks like in our industry with regard to launches that are in or around the respiratory space. And using those analogs, which we've mentioned a number of times, we take note that the first 2 full quarters combined usually end up in the high double-digit millions and those products that have accomplished that represents some of the strongest launches that you can find in the commercial setting. So those are our ambitions. It's certainly not something we're providing guidance on today, and we're cautious about interpreting the first 6 weeks of data that we have because it really is not a lot, and there's a lot of sorting out going on at this stage as different physicians are taking different approaches to the medicine that the market access is getting sorted out. And while that, as Roger said, can be easier at the start once the criteria gets established and in force that can change that dynamic. So I would say we're very pleased with the breadth of prescribing. We now want to see the depth of prescribing take hold as we move into the adoption phase. That will take several quarters in my mind. But we'll be looking very carefully at Q4, and we should have enough data in Q4 to really begin to discern some of these issues and be much more specifically responsive to your question. I just -- at this point, I think we're just cautious about over-interpreting what is a quarter that includes inventory build. It includes first trials. It includes certainly some patients who are waiting for day 1 for the medicine to arrive and some physicians looking to prescribe it right away. But as that dissipates, what is the real landscape look like. And that's something we're going to have to learn over time.

Your next question comes from the line of Graig Suvannavejh with Mizuho.

This is Sam on for Graig. Congrats on the awesome launch. Maybe just a follow-up with Ben's question on the more mild to moderate population for BRINSUPRI. I know it's still early days, but curious have you seen any payers start to restrict use to patients who have less than two more pulmonary exacerbations?

So I want to be clear, the focus is on those with two or more out of the gate. That's really where we think the medicine is going to be quite obviously, the most successful because you'll higher exacerbations, the better the chance to show the reduction in those events. But it's equally important for everyone to appreciate that these other secondary endpoints where we were highly statistically significant in Phase III in the 10 and 25-milligram arms are really quite relevant. That is how long before your next exacerbation, the probability that you may have no exacerbations in the next year. These kinds of metrics, which were favorable to BRINSUPRI, I think also bear on the consideration of the physicians when they're trying to disc who they're going to prescribe this for. But to be clear, out of the gate, I think it's appropriate, the focus is squarely on those with two or more exacerbations. I don't know, Roger, if you want to comment or anything you've heard from the field on those with less than two.

No, I think that, that characterizes it will. And we do see the patients who are exacerbating the ones that are in front of the physicians. And I do think that as we go forward and that criteria from pairs gets formalized they're going to be looking to mimic the clinical trial and what we saw with ASPEN with that two or more exacerbations. So the focus really has not been on sort of the patients who don't have those recorded exacerbations at this point. The enthusiasm from physicians for those patients who have been waiting for this is those patients who are frequent exacerbators. And that's what we primarily believe is going through at this point.

And your next question comes from the line of Andy Chen with Wolfe Research.

Brandon, on for Andy. On HS, will you be sharing HiSCR data at the top line readout? And how do you imagine brenso fitting into the HS landscape?

So I'm sorry, I'm not sure I caught the first part of the question. Will we be sharing what?

HiSCR data.

The HiSCR data. So Martina, you want to describe the different secondary end points we're going to be looking at?

Yes. So the HiSCR, we will look at the secondary endpoint of the HiSCR 50 as well as for a HiSCR 75. And right now, we anticipate that would not necessarily be something that you see right away at the week 16. You will see some 16-week treatment period, but what that really should indicate for us is we will go on to 52 weeks, and it's the HiSCR at 52 weeks both for 50 and 75 that we will be also looking at for Phase III. But you will see it at the top line results, the 16-week treatment period.