Full Year 2025 Insmed Inc Earnings Call

February 19, 2026

Speaker #1: Thank you for standing by and welcome to the INSMED 4th Quarter and Full Year 2025 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise.

Operator: Thank you for standing by, and welcome to the Insmed Fourth Quarter and Full Year 2025 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press Star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press Star one. Thank you. I'd now like to turn the call over to Bryan Dunn, Head of Investor Relations. You may begin.

Speaker #1: After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star, followed by the number 1 on your telephone keypad.

Speaker #1: If you would like to withdraw your question, again, press star 1. Thank you. I'd now like to turn the call over to Bryan Dunn, Head of Investor Relations.

Speaker #1: You may begin.

Speaker #2: Thank you, Rob. Good day, everyone, and welcome to today's conference call to discuss INSMED's 4th Quarter and Full Year 2025 Financial Results and provide an update on our business.

Operator: Thank you, Rob. Good day, everyone, and welcome to today's conference call to discuss Insmed's Q4 and full year 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. 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, and Sara Bonstein, Chief Financial Officer.

Bryan Dunn: Thank you, Rob. Good day, everyone, and welcome to today's conference call to discuss Insmed's Q4 and full year 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. 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, and Sara Bonstein, Chief Financial Officer.

Speaker #2: 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 their projections discussed.

Speaker #2: Please refer to our filings with the Securities and Exchange Commission for more information. The information we will discuss on today's call is meant for the benefit of the investment community.

Speaker #2: 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, and Sara Bonstein, Chief Financial Officer.

Speaker #2: 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.

Operator: 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.

Bryan Dunn: 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.

Speaker #3: Thank you, Bryan. Good morning, everyone, and thank you for joining us. 2025 was an exceptional year for Insmed, defined by extraordinary execution and transformative impact.

Will Lewis: Thank you, Bryan. Good morning, everyone, and thank you for joining us. 2025 was an exceptional year for Insmed, defined by extraordinary execution and transformative impact. Commercially, we witnessed the approval of BRINSUPRI and its stunning early months of launch performance, as well as the continued global performance of ARIKAYCE, which showed significant acceleration from commercial efforts in Europe and especially Japan. Clinically, we saw best-in-class performance from TPIP, entered two new gene therapies into the clinic for DMD and ALS, and completed the acquisition of INS1148. These accomplishments represent a significant expansion of our clinical pipeline, despite the discontinuation of CRSsNP program last quarter. We enter 2026 with momentum that positions Insmed for sustained leadership in both bronchiectasis and NTM. In the year ahead, we intend to accelerate and expand the US launch of BRINSUPRI while continuing to grow ARIKAYCE.

Speaker #3: Commercially, we witnessed the approval of Brinsupri and its stunning early months of launch performance. As well as the continued global performance of Ericase, which showed significant acceleration from commercial efforts in Europe and especially Japan.

Speaker #3: Clinically, we saw best-in-class performance from TPIP, entered two new gene therapies into the clinic for DMD and ALS, and completed the acquisition of INS-1148.

Speaker #3: These accomplishments represent a significant expansion of our clinical pipeline, despite the discontinuation of the CRS without nasal polyps program last quarter. We entered 2026 with momentum that positions Insmed for sustained leadership in both bronchiectasis and NTM.

Speaker #3: In the year ahead, we intend to accelerate and expand the US launch of Brinsupri while continuing to grow Ericase. Rarely does a company have the opportunity to own an entire disease category by virtue of having the first approved medicine in a disease with no competition on the immediate horizon.

Will Lewis: Rarely does a company have the opportunity to own an entire disease category by virtue of having the first approved medicine in a disease with no competition on the immediate horizon. Insmed enjoys two such opportunities in bronchiectasis and NTM, both of which also share a similar call point among pulmonologists. To this strong foundation, we intend to pursue other first or best-in-class therapies within our three target therapeutic areas, which include respiratory, inflammation, and immunology, and neurology and other rare diseases. Today, we are pleased to announce revenue guidance for BRINSUPRI of at least $1 billion in 2026. We are confident providing this guidance earlier than expected due to the additional visibility we have gained into the market access environment and the early performance we have seen from BRINSUPRI so far this year.

Speaker #3: INSMED enjoys two such opportunities in bronchiectasis and NTM, both of which also share a similar call point among pulmonologists. To the strong foundation we intend to pursue other first or best-in-class therapies within our three target therapeutic areas, which include respiratory, inflammation, and immunology, and neurology and other rare diseases.

Speaker #3: Today, we are pleased to announce revenue guidance for Brinsupri of at least $1 billion in 2026. We are confident providing this guidance earlier than expected due to the additional visibility we have gained into the market access environment and the early performance we have seen from Brinsupri so far this year.

Speaker #3: To our knowledge, only 15 drug launches in history have been able to surpass the billion-dollar mark in their second through fifth full quarters of launch, and every company that has achieved that milestone has gone on to reach a market valuation of $70 billion or more.

Will Lewis: To our knowledge, only 15 drug launches in history have been able to surpass the $1 billion mark in their second through fifth full quarters of launch, and every company that has achieved that milestone has gone on to reach a market valuation of $70 billion or more. Coupled with another expected strong year of performance from ARIKAYCE, we anticipate total company revenue in 2026 to be more than double the revenue we produced in 2025. This guidance gives us confidence that we can achieve cash flow positivity without needing to raise additional capital. However, we may choose to source capital as necessary to support new business development, internal programs, or other potentially value-creating initiatives. We are currently evaluating several such opportunities and will continue to do so as we prudently seek to expand our pipeline. Let us now dive deeper into BRINSUPRI.

Speaker #3: Coupled with another expected strong year of performance from Ericase, we anticipate total company revenue in 2026 to be more than double the revenue we produced in 2025.

Speaker #3: This guidance gives us confidence that we can achieve cash flow positivity without needing to raise additional capital. However, we may choose to source capital as necessary to support new business development, internal programs, or other potentially value-creating initiatives.

Speaker #3: We are currently evaluating several such opportunities, and we'll continue to do so as we prudently seek to expand our pipeline. Let us now dive deeper into Brinsupri.

Speaker #3: In 2025, the US launch of Brinsupri surpassed even our most ambitious expectations. Pre-launch, we set a very high bar for what we believed Brinsupri could achieve, using a basket of historically strong respiratory launches as our guide.

Will Lewis: In 2025, the US launch of BRINSUPRI surpassed even our most ambitious expectations. Pre-launch, we set a very high bar for what we believe BRINSUPRI could achieve using a basket of historically strong respiratory launches as our guide. With $144.6 million in net revenue in its first full quarter, I'm proud to say that BRINSUPRI is exceeding that bar. And let me be clear, the launch continues to go well, and the team continues to execute at a very high level. As with many successful medicines, the shape of the launch from one month to another can be inherently variable, but the overall trajectory for this launch is strongly up and to the right, and we believe BRINSUPRI has the potential to be among the best, if not the best, specialty respiratory launch ever.

Speaker #3: With 144.6 million in net revenue in its first full quarter, I'm proud to say that Brinsupri is exceeding that bar. And let me be clear: the launch continues to go well, and the team continues to execute at a very high level.

Speaker #3: As with many successful medicines, the shape of the launch from one month to another can be inherently variable. But the overall trajectory for this launch is strongly up and to the right, and we believe Brinsupri has the potential to be among the best, if not the best, specialty respiratory launch ever.

Speaker #3: Let me now take a moment to illustrate where we expect the Brinsupri opportunity to evolve over time. In these early months of the launch, we see Brinsupri establishing itself at the forefront of treating bronchiectasis with no competition for several years.

Will Lewis: Let me now take a moment to illustrate where we expect the BRINSUPRI opportunity to evolve over time. In these early months of the launch, we see BRINSUPRI establishing itself at the forefront of treating bronchiectasis with no competition for several years. We had previously framed out a peak sales estimate above $5 billion for this indication, and everything we have seen so far from this launch has only added to our conviction that the opportunity is at least that large. But I want to emphasize this point, we believe there may be much more. Let's get specific. We previously defined the total addressable market in the US based on BRINSUPRI's label as 500,000 currently diagnosed patients with non-CF bronchiectasis.

Speaker #3: We had previously framed out a peak sales estimate above $5 billion for this indication and everything we have seen so far from this launch has only added to our conviction that the opportunity is at least that large.

Speaker #3: But I want to emphasize this point: we believe there may be much more. Let's get specific. We've previously defined the total addressable market in the US based on Brinsupri's label as 500,000 currently diagnosed patients with non-CF bronchiectasis.

Speaker #3: Within that diagnosed population, we estimate that approximately half, or 250,000 patients, have had two or more exacerbations in the last 12 months, matching the profile of the patients who participated in our clinical trials.

Will Lewis: Within that diagnosed population, we estimate that approximately half, or 250,000 patients, have had two or more exacerbations in the last 12 months, matching the profile of the patients who participated in our clinical trials. Based on those figures, the roughly 11,550 new patients who have started treatment with BRINSUPRI in 2025 represent less than 5% of that patient population. So there remains an enormous amount of runway within that initial total addressable market. And as a reminder, the greater than $5 billion peak sales estimate was based on us successfully addressing these 250,000 patients only.

Speaker #3: Based on those figures, the roughly 11,550 new patients who have started treatment with Brinsupri in 2025 represent less than 5% of that patient population, so there remains an enormous amount of runway within that initial total addressable market.

Speaker #3: And as a reminder, the greater than $5 billion peak sales estimate was based on us successfully addressing these 250,000 patients only. In addition, we believe that, over time, more of the remaining 250,000 currently diagnosed patients with fewer than two exacerbations will start to move into the category of those who have had two or more exacerbations in a 12-month period.

Will Lewis: In addition, we believe that over time, more of the remaining 250,000 currently diagnosed patients with less than two exacerbations will start to move into the category of those who have had two or more exacerbations in a 12-month period. This is due to the progressive nature of the disease and better patient reporting and documentation of exacerbation events now that there is an available treatment. This belief is supported by real-world data. In a two-year study of claims data for nearly 15,000 patients with bronchiectasis, about 47% had two or more exacerbations in the first year of follow-up. Then in the second year, another 9% joined that group, meaning that 56% of the study patients had two or more exacerbations in either the first or second year.

Speaker #3: This is due to the progressive nature of the disease and better patient reporting and documentation of exacerbation events now that there is an available treatment.

Speaker #3: This belief is supported by real-world data. In a two-year study of claims data for nearly 15,000 patients with bronchiectasis, about 47% had two or more exacerbations in the first year of follow-up.

Speaker #3: Then, in the second year, another 9% joined that group, meaning that 56% of studied patients had two or more exacerbations in either the first or second year.

Speaker #3: Based on that study, it is our expectation that patients will continue to move into the two-plus category over time and this would represent upside to our peak sales estimates.

Will Lewis: Based on that study, it is our expectation that patients will continue to move into the two-plus category over time, and this would represent upside to our peak sales estimates. Now, if I can leave you with one item to focus on, it is this: There are 32 million diagnosed patients with COPD or asthma in the US. We believe that many of those patients could have undiagnosed bronchiectasis and, as a result, may continue to exacerbate despite treatment with standard of care for those diagnoses. I would encourage you to consider and assess this potential for yourself. Recognizing the size of that opportunity, we are turning our attention to outreach and education to physicians in the hopes that they can assess these patients for the presence of bronchiectasis.

Speaker #3: Now, if I can leave you with one item to focus on, it is this: there are 32 million diagnosed patients with COPD or asthma in the US.

Speaker #3: We believe that many of those patients could have undiagnosed bronchiectasis and, as a result, may continue to exacerbate despite treatment with standard of care for those diagnoses.

Speaker #3: I would encourage you to consider and assess this potential for yourself. Recognizing the size of that opportunity, we are turning our attention to outreach and education to physicians in the hopes that they can assess these patients for the presence of bronchiectasis.

Speaker #3: The potential additional patients from these populations who would be on-label for Brinsupri, if they are confirmed to have bronchiectasis, dwarfs the initial total addressable market we have just been discussing.

Will Lewis: The potential additional patients from these populations, which would be on label for BRINSUPRI if they are confirmed to have bronchiectasis, dwarfs the initial total addressable market we have just been discussing. We are currently working on a number of different programs to advance the exploration and quantification of these patients. This effort will be supported by evidence generation in several large respiratory centers, who intend to use retrospective data to identify bronchiectasis in patients diagnosed with COPD and asthma who are still exacerbating. We are also creating dedicated teams within our medical and commercial operations to identify these potential patients, given the substantial populations they represent.

Speaker #3: We are currently working on a number of different programs to advance the exploration and quantification of these patients. This effort will be supported by evidence generation in several large respiratory centers who intend to use retrospective data to identify bronchiectasis in patients diagnosed with COPD and asthma who are still exacerbating.

Speaker #3: We are also creating dedicated teams within our medical and commercial operations to identify these potential patients, given the substantial population they represent. As many of you know, historical medical literature on this topic provides a wide range of estimates.

Will Lewis: As many of you know, historical medical literature on this topic provides a wide range of estimates, but a more recent publication that looks specifically at the overlap between COPD, asthma, and bronchiectasis suggests that bronchiectasis could be involved in 30% to over 50% of patients with moderate to severe COPD and in 25% to 40% of patients with severe asthma. These patients may not have received attention or been identified in the past because until BRINSUPRI came along, there had been no medicine that physicians could turn to upon diagnosis. As we're able to identify patients that may benefit from BRINSUPRI from within this broader population, we have a chance to help physicians deliver what we believe could be a game-changing medicine for the benefit of their patients.

Speaker #3: But a more recent publication that looks specifically at the overlap between COPD, asthma, and bronchiectasis suggests that bronchiectasis could be involved in 30 to over 50 percent of patients with moderate to severe COPD and in 25 to 40 percent of patients with severe asthma.

Speaker #3: These patients may not have received attention or been identified in the past because until Brinsupri came along, there have been no medicine that physicians could turn to upon diagnosis.

Speaker #3: As we're able to identify patients that may benefit from Brinsupri from within this broader population, we have a chance to help physicians deliver what we believe could be a game-changing medicine for the benefit of their patients.

Speaker #3: It is an enormous opportunity to serve patients, and it will take several years to more fully manifest, but it has the potential to expand Brinsupri's impact by orders of magnitude.

Will Lewis: It is an enormous opportunity to serve patients, and it will take several years to more fully manifest, but it has the potential to expand BRINSUPRI's impact by orders of magnitude. This is something we are actively working on and will continue to monitor, but it is our belief that we could begin to see these patients as early as the end of this year within the pulmonary practices we already call on, and more evidently in 2027 and beyond. Let me now take a step back and describe what we are seeing within the launch to date. Today, we are still in what I would call the exploration stage of the launch.

Speaker #3: This is something we are actively working on and will continue to monitor, but it is our belief that we could begin to see these patients as early as the end of this year within the pulmonary practices we already call on, and more evidently in 2027 and beyond.

Speaker #3: Let me now take a step back and describe what we are seeing within the launch to date. Today, we are still in what I would call the exploration stage of the launch.

Speaker #3: This is a new medicine and, as is customary, physicians often want to try it out on a patient or two to see how it works, assess safety, and then determine how much more broadly they intend to prescribe.

Will Lewis: This is a new medicine, and as is customary, physicians often want to try it out on a patient or two to see how it works, assess safety, and then determine how much more broadly they intend to prescribe. For example, of the 4,000 physicians who have written a prescription through the end of 2025, nearly half had prescribed BRINSUPRI to just a single patient. As those first patients return to their pulmonologist and share their experience with the treatment early this year, this should play an outsized role in their physician's interest and willingness to write again. To date, we have heard very positive feedback through our interactions with physicians and directly from patients through our support services, as well as through the patient experiences that have been shared in public forums or on social media....

Speaker #3: For example, of the 4,000 physicians who have written a prescription through the end of 2025, nearly half had prescribed Brinsupri to just a single patient.

Speaker #3: As those first patients return to their pulmonologist and share their experience with the treatment early this year, this should play an outsized role in their physician's interest and willingness to write again.

Speaker #3: To date, we have heard very positive feedback through our interactions with physicians and directly from patients through our support services, as well as through the patient experiences that have been shared in public forums or on social media.

Speaker #3: It can often take several months for patients to return to their physician's offices to be able to convey these experiences, but this positive early feedback suggests that the knock-on effect of these experiences should start to result in additional prescribing behavior by the second quarter, given the large number of new patients that were added in the fourth quarter of 2025.

Will Lewis: It can often take several months for patients to return to their physician's offices to be able to convey these experiences, but this positive early feedback suggests that the knock-on effect of these experiences should start to result in additional prescribing behavior by Q2, given the large number of new patients that were added in Q4 2025. We believe these positive experiences with the current diagnosed bronchiectasis population should also increase the likelihood that physicians will be receptive to proactively tracking exacerbations and screening their COPD and asthma patients for bronchiectasis. Turning now to the mechanics of how patients gain access to BRINSUPRI. A critical element of successful launches is favorable payer access dynamics, and I am pleased to say that this is progressing very well.

Speaker #3: We believe these positive experiences with the current diagnosed bronchiectasis population should also increase the likelihood that physicians will be receptive to proactively tracking exacerbations and screening their COPD and asthma patients for bronchiectasis.

Speaker #3: Turning now to the mechanics of how patients gain access to Brinsupri. A critical element of successful launches is favorable payer access dynamics, and I am pleased to say that this is progressing very well.

Speaker #3: In fact, over 90% of targeted patient lives have access to getBrinsupri reimbursed either through a documented payer policy or medical exception. We chose to engage payers in an effort to encourage them to make access for appropriate patients as frictionless as possible.

Will Lewis: In fact, over 90% of targeted patient lives have access to get BRINSUPRI reimbursed, either through a documented payer policy or medical exception. We chose to engage payers in an effort to encourage them to make access for appropriate patients as frictionless as possible. For those who have been willing to engage with us and settle on simple, attestation-based prior authorization and reauthorization criteria, we have offered modest rebates. Others have chosen to require documentation within their medical policies, which typically means requesting documentation of the CT scan and proof of two or more exacerbations. Importantly, we have seen a very high payer approval rate so far, even for payers requiring documentation, which is very promising. Given our long history with ARIKAYCE, which even now is primarily reimbursed through medical exception, we've become skilled at providing education to healthcare providers and their offices about documentation and process requirements.

Speaker #3: For those who have been willing to engage with us and settle on simple, attestation-based prior authorization and reauthorization criteria, we have offered modest rebates.

Speaker #3: Others have chosen to require documentation within their medical policies, which typically means requesting documentation of the CT scan and proof of two or more exacerbations.

Speaker #3: Importantly, we have seen a very high payer approval rate so far, even for payers requiring documentation, which is very promising. Given our long history with Airacase—which, even now, is primarily reimbursed through medical exception—we have become skilled at providing education to healthcare providers and their offices about documentation and process requirements.

Speaker #3: We expect these high approval rates to continue in the months ahead as physicians and their staff become more accustomed to the payer reimbursement requirements.

Will Lewis: We expect these high approval rates to continue in the months ahead as physicians and their staff become more accustomed to the payer reimbursement requirements. While we expect contracts to continue to officially go into effect over the course of the first half of this year, we've concluded enough of these negotiations to feel confident in the general direction of the market access landscape for BRINSUPRI. I am pleased to say this landscape is aligned with our pre-launch expectations, with broad access to the treatments for appropriate patients and either physician attestation or manageable documentation required for reimbursement in most cases. In summary, the BRINSUPRI launch continues to be very strong.

Speaker #3: While we expect contracts to continue to officially go into effect over the course of the first half of this year, we have concluded enough of these negotiations to feel confident in the general direction of the market access landscape for Brinsupri.

Speaker #3: I am pleased to say that this landscape is aligned with our pre-launch expectations, with broad access to the treatment for appropriate patients, and either physician attestation or manageable documentation required for reimbursement in most cases.

Speaker #3: In summary, the Brinsupri launch continues to be very strong. The rate of patient adds, new physicians, and manageable market access dynamics gives us comfort that from the initial patients we are targeting, we see a clear path to reaching our stated peak sales goal of more than $5 billion, with potentially significant upside from the adjacent populations outlined a few moments ago that could take that peak sales number much higher.

Will Lewis: The rate of patient adds, new physicians, and manageable market access dynamics gives us comfort that from the initial patients we are targeting, we see a clear path to reaching our stated peak sales goal of more than $5 billion, with potentially significant upside from the adjacent populations outlined a few moments ago that could take that peak sales number much higher. We'll have much more to say in the quarters to come as we gain a clearer picture of how big and when those additional patients may be diagnosed and become on label for BRINSUPRI. The opportunity itself is one that any biotech company would be fortunate to have, and we intend to aggressively resource the launch to maximize its potential. Now let me spend a moment on ARIKAYCE. Our commercial teams continued to do an excellent job of driving growth of the product.

Speaker #3: We will have much more to say in the quarters to come as we gain a clearer picture of how big and when those additional patients may be diagnosed and become on-label for Brinsupri.

Speaker #3: The opportunity itself is one that any biotech company would be fortunate to have, and we intend to aggressively resource the launch to maximize its potential.

Speaker #3: Now let me spend a moment on Airacase. Our commercial teams continue to do an excellent job of driving growth of the product. Japan had a particularly impressive 2025, delivering 40% growth compared to 2024 and contributing more than a quarter of Airacase's global revenues.

Will Lewis: Japan had a particularly impressive 2025, delivering 40% growth compared to 2024 and contributing more than a quarter of ARIKAYCE's global revenues. In Europe, ARIKAYCE grew even faster, albeit from a more modest revenue base. This strong commercial execution sets the stage for ARIKAYCE's next clinical readout, the Phase 3 ENCORE trial, which we expect to announce in March or April of this year. Success in ENCORE could open an opportunity to increase the addressable market for ARIKAYCE from around 30,000 patients today to more than 200,000 patients. Let me now switch gears and spend a moment on TPIP, which was significantly de-risked by strong clinical data in 2025, opening up the opportunity for us to pursue four Phase 3 clinical programs in parallel.

Speaker #3: In Europe, Airacase grew even faster albeit from a more modest revenue base. This strong commercial execution sets the stage for Airacase's next clinical readout to phase three on-core trial, which we expect to announce in March or April of this year.

Speaker #3: Success in on-core could open an opportunity to increase the addressable market for Airacase from around 30,000 patients today to more than 200,000 patients. Let me now switch gears and spend a moment on TPIP, which was significantly de-risked by strong clinical data in 2025, opening up the opportunity for us to pursue four phase three clinical programs in parallel.

Speaker #3: We are very excited to announce that last month we were informed by the FDA's Office of Orphan Drug Products Development of their decision to grant orphan drug designation to troposinopalmitol for the treatment of pulmonary arterial hypertension.

Will Lewis: We are very excited to announce that last month we were informed by the FDA's Office of Orphan Drug Products Development of their decision to grant orphan drug designation to treprostinil palmitil for the treatment of pulmonary arterial hypertension. So you can understand the basis for this designation in their own words, I read here from the actual letter we received from the FDA. Quote, Our decision to grant designation is based on the plausible hypothesis that your drug may be clinically superior to the same drugs already approved for the same indication, because your drug may be more effective due to greater placebo-corrected improvement in the six-minute walk distance compared to other approved oral or inhaled formulations of treprostinil, and by means of a major contribution to patient care compared to the approved subcutaneous and intravenous formulation of treprostinil. Close quote.

Speaker #3: So you can understand the basis for this designation, in their own words, I read here from the actual letter we received from the FDA.

Speaker #3: "Our decision to grant designation is based on the plausible hypothesis that your drug may be clinically superior to the same drugs already approved for the same indication because your drug may be more effective due to greater placebo-corrected improvement in the six-minute walk distance compared to other approved oral or inhaled formulations of troposinol and by means of a major contribution to patient care compared to the approved subcutaneous and intravenous formulation of troposinol." This decision, which was based on the FDA's assessment of our phase two data released last year, is a striking validation that our belief that TPIP has the plausible chance to be a meaningfully differentiated treatment compared to other troposinol options.

Will Lewis: This decision, which was based on the FDA's assessment of our Phase 2 data released last year, is a striking validation that our belief that TPIP has the plausible chance to be a meaningfully differentiated treatment compared to other treprostinil options. In our view, this supports our long-held conviction that TPIP could become the prostanoid of choice for physicians and patients. Last month, we presented the trial design for our PALM-PAH Phase 3 trial of TPIP in patients with PAH at the PVRI conference in Dublin. Recall that the FDA agreed, based on the strength of the Phase 2 results, that we would need just one Phase 3 trial powered at the standard 0.05 alpha for a registrational submission. On this slide, you can see a depiction of the trial design for PALM-PAH.

Speaker #3: In our view, this supports our long-held conviction that TPIP could become the prostanoid of choice for physicians and patients. Last month, we presented the trial design for our PALM PAH Phase 3 trial of TPIP in patients with PAH at the PVRI conference in Dublin.

Speaker #3: Recall that the FDA agreed, based on the strength of the phase two results, that we would need just one phase three trial powered at the standard 0.05 alpha for a registrational submission.

Speaker #3: On this slide, you can see a depiction of the trial design for PALM PAH. While much of the design is similar to our phase two trial, there are some key differences.

Will Lewis: While much of the design is similar to our phase II trial, there are some key differences. First, the trial has a longer treatment period of 24 weeks versus 16 weeks in phase II. This longer treatment period is intended to provide patients with a practical titration window, given that this trial will allow patients to dose up to 1,280 mcg or double the highest dose used in phase II. To put that high dose into perspective, 1,280 mcg of TPIP, after subtracting the weight of the 16-carbon chain, contains about 813 mcg of treprostinil... That is more than 3 times the highest labeled daily dose of Tyvaso DPI for patients that fully comply with the 4 doses required per day with that treatment. Another difference is that the phase III study will allow patients to be on background sotatercept.

Speaker #3: First, the trial has a longer treatment period of 24 weeks versus 16 weeks in phase two. This longer treatment period is intended to provide patients with a practical titration window given that this trial will allow patients to dose up to 1,280 micrograms or double the highest dose used in phase two.

Speaker #3: To put that high dose into perspective, 1,280 micrograms of TPIP after subtracting the weight of the 16-carbon chain contains about 813 micrograms of troposinol.

Speaker #3: That is more than three times the highest labeled daily dose of tivazodipi for patients that fully comply with the four doses required per day with that treatment.

Speaker #3: Another difference is that the phase three study will allow patients to be on background sotatercept. Enrollment of those patients will be capped at 20% of the overall population and stratified to ensure balance between treatment arms.

Will Lewis: Enrollment of those patients will be capped at 20% of the overall population and stratified to ensure balance between treatment arms. Finally, the primary endpoint of six-minute walk distance will be measured 1 to 3 hours post-dose to approximate TPIP's peak effect, similar to trials of other treprostinil products. PROF measurements will also be captured as secondary endpoints. We are incredibly excited to get this trial started in the first half of this year. To recap, I am very pleased with where we are as a company. The BRINSUPRI launch continues to go well, allowing us to announce revenue guidance for 2026 of at least $1 billion for that therapy. When combined with the strong performance that we expect for ARIKAYCE in 2026, we expect to produce revenue on a company-wide basis that more than doubles from last year.

Speaker #3: Finally, the primary endpoint of six-minute walk distance will be measured one to three hours post-dose to approximate TPIP's peak effect similar to trials of other troposinol products.

Speaker #3: TROF measurements will also be captured as secondary endpoints. We are incredibly excited to get this trial started in the first half of this year.

Speaker #3: To recap, I am very pleased with where we are as a company. The Brinsupri launch continues to go well, allowing us to announce revenue guidance for 2026 of at least $1 billion for that therapy.

Speaker #3: When combined with the strong performance that we expect for Airacase in 2026, we expect to produce revenue on a company-wide basis that more than doubles from last year.

Speaker #3: And even that could be just the beginning, as we await a near-term pivotal readout for Airacase that could expand its label, and we work to identify new patients who could benefit from Brinsupri.

Will Lewis: Even that could be just the beginning, as we await a near-term pivotal readout for ARIKAYCE that could expand its label, and we work to identify new patients who could benefit from BRINSUPRI. For TPIP, we have received an orphan drug designation for treprostinil palmitil for the treatment of PAH, and have released the phase III trial design for that indication. If successful, the FDA has indicated that this single phase III would be sufficient to support a filing for TPIP in patients with PAH. Finally, we have a strong and growing pipeline of potentially first or best-in-class investigational programs behind the ones we've spoken about today, many of which should also begin to contribute catalysts over the next year and beyond. With that, let me turn the call over to Sara.

Speaker #3: For TPIP, we have received an orphan drug designation for troposinopalmitol for the treatment of PAH and have released the phase three trial design for that indication.

Speaker #3: If successful, the FDA has indicated that this single Phase 3 would be sufficient to support a filing for TPIP in patients with PAH. Finally, we have a strong and growing pipeline of potentially first- or best-in-class investigational programs behind the ones we've spoken about today.

Speaker #3: Many of which should also begin to contribute catalysts over the next year and beyond. With that, let me turn the call over to Sara.

Speaker #2: Thank you, Will, and good morning, everyone. Given that Will has already walked you through our 2026 revenue guidance for Airacase and Brinsupri, let me provide you with a few additional comments on our expected growth synapse in 2026.

Sara Bonstein: Thank you, Will, and good morning, everyone. Given that Will has already walked you through our 2026 revenue guidance for ARIKAYCE and BRINSUPRI, let me provide you with a few additional comments on our expected gross-to-net in 2026. In the past, we have highlighted a range of 25 to 35% as a reasonable analog for BRINSUPRI's gross-to-net at launch. This range was based on precedent launches and the impact of new catastrophic coverage requirements under IRA legislation. Today, we believe we have good visibility into where payer contracting is headed and are now positioned to provide a gross-to-net guidance range of mid-20s to low 30s for BRINSUPRI in 2026.

Speaker #2: In the past, we have highlighted a range of 25 to 35 percent as a reasonable analog for Brinsupri's growth synapse at launch. This range was based on precedent launches and the impact of new catastrophic coverage requirements under IRA legislation.

Speaker #2: Today, we believe we have good visibility into where payer contracting is headed and are now positioned to provide a growth synapse guidance range of mid-20s to low 30s for Brinsupri in 2026.

Sara Bonstein: Importantly, our 2025 actual gross to net for BRINSUPRI was also in that range, which implies that the rebating expected to go into effect into 2026 will be modest and is therefore not anticipated to have a significant effect on the overall GTN of the product. For ARIKAYCE, GTN for 2026 is expected to range from the low to mid-20s, a slight increase from 2025, due primarily to the impact of the small manufacturer phase-in and other provisions under IRA. Let me spend a moment on our cash position. As of the end of 2025, we had approximately $1.4 billion in cash, cash equivalents, and marketable securities.

Speaker #2: Importantly, our 2025 actual growth synapse for Brinsupri was also in that range, which implies that the rebating expected to go into effect in 2026 will be modest and is therefore not anticipated to have a significant effect on the overall GTN of the product.

Speaker #2: For Airacase, GTN for 2026 is expected to range from the low to mid-20s, a slight increase from 2025 due primarily to the impact of the small manufacturer phase-in and other provisions under IRA.

Speaker #2: Let me spend a moment on our cash position. As of the end of 2025, we had approximately 1.4 billion dollars in cash-cash equivalents and marketable securities.

Speaker #2: Cash burn in Q4 included approximately 70 million dollars of one-time items, largely attributed to the asset acquisition of INS 1148 and the milestone payment to AstraZeneca related to Brinsupri's US approval.

Sara Bonstein: Cash burn in Q4 included approximately $70 million of one-time items, largely attributed to the asset acquisition of INS1148 and the milestone payment to AstraZeneca related to BRINSUPRI's US approval. Excluding those one-time items and the cash received related to stock option exercises in the period, our underlying cash burn for the quarter was similar to the underlying burn levels that we saw in the prior quarter. Keep in mind that only a portion of the BRINSUPRI revenue we recognized this quarter had been received in cash as of December 31, so our cash burn does not 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 other programs from across our portfolio that are expected to continue to ramp in the near and medium term.

Speaker #2: Excluding those one-time items and the cash received related to stock option exercises in the period, our underlying cash burn for the quarter was similar to the underlying burn levels that we saw in the prior quarter.

Speaker #2: Keep in mind that only a portion of the Brinsupri revenue we recognize this quarter had been received in cash as of December 31st, so our cash burn does not reflect that full benefit.

Speaker #2: 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 other programs from across our portfolio that are expected to continue to ramp in the near and medium term.

Speaker #2: Finally, I would like to re-emphasize the statement Will made earlier as it relates to our pathway to profitability. Based on our existing development plan and the strength of our commercial engine and its revenue capabilities, I am confident we can achieve cash flow positivity without needing to access additional capital.

Sara Bonstein: Finally, I would like to reemphasize the statement Will made earlier as it relates to our pathway to profitability. Based on our existing development plan and the strength of our commercial engine and its revenue capabilities, I am confident we can achieve cash flow positivity without needing to access additional capital. That said, I will remind you that we have and will continue to invest in appropriate business development opportunities as well as internal programs, and therefore may choose to source additional capital to advance and expand our pipeline in support of additional future value creation. Moving now to other relevant financial metrics for Q4, which are displayed on this slide.

Speaker #2: That said, I will remind you that we have, and will continue to, invest in appropriate business development opportunities as well as internal programs, and therefore may choose to source additional capital to advance and expand our pipeline and support additional future value creation.

Speaker #2: Moving now to other relevant financial metrics for the fourth quarter, which are displayed on this slide. Cost of product revenues in the fourth quarter of 2025 was 44.2 million dollars or 16.8% of revenues, which is lower on a percentage basis based on a historical performance reflecting the positive contributions of Brinsupri to the company's gross margin profile.

Sara Bonstein: Cost of product revenues in the fourth quarter of 2025 was $44.2 million or 16.8% of revenues, which is lower on a percentage basis based on our historical performance, reflecting the positive contributions of BRINSUPRI to the company's gross margin profile. Additionally, as expected, research and development, and SG&A expenses increased this quarter compared to prior-year period, due to the necessary investments made to support the US launch of BRINSUPRI and to continue to fund our growing pipeline. In closing, I am pleased to report that Insmed remains in a strong financial position, providing us with the capacity to pursue our ambitious goal to expand our reach and our impact on patients. We look forward to continuing to utilize our resources to pursue the potentially value-creating opportunities we have in front of us.

Speaker #2: Additionally, as expected, research and development and SG&A expenses increased this quarter compared to the prior year period due to the necessary investments made to support the U.S. launch of Brinsupri and to continue to fund our growing pipeline.

Speaker #2: In closing, I am pleased to report that Insmed remains in a strong financial position, providing us with the capacity to pursue our ambitious goal to expand our reach and our impact on patients.

Speaker #2: We look forward to continuing to utilize our resources to pursue the potentially value-creating opportunities we have in front of us. We would now like to open the call to your questions.

Sara Bonstein: We would now like to open the call to your questions. Operator, may we take the first question, please?

Speaker #2: Operator, may we take the first question, please?

Speaker #3: Thank you. We will now begin the question and answer session. If you'd like to ask a question, please press star one in your telephone keypad.

Operator: Thank you. We will now begin the question-and-answer session. If you'd like to ask a question, please press star one on your telephone keypad. We ask that you please limit yourself to one question. You may queue for any follow-up questions. Your first question today comes from the line of Joe Schwartz from Leerink Partners. Your line is open.

Speaker #3: We ask that you please limit yourself to one question. You may requeue for any follow-up questions. Your first question today comes from a line of Joe Schwartz from Laring Partners.

Speaker #3: Your line is open.

Speaker #4: Great. Thanks so much, and congrats on the very strong performance. It certainly seems like the TAM for Brinsupri has a lot of room to expand with a very well-designed strategy to identify patients with COPD or asthma who are exacerbating with bronchiectasis, but might not yet be identified as such.

[Analyst]: ... Great. Thanks so much, and congrats on the very strong performance. It certainly seems like the TAM for BRINSUPRI has a lot of room to expand with a very well-designed strategy to identify patients with COPD or asthma who are exacerbating with bronchiectasis, but might not yet be identified as such. I look forward to hearing about that progress on that front as you embark on this initiative, but I was wondering if you have any plans to develop other DPP1 inhibitors within respiratory disease in order to expand your franchise further, and if so, how do these other agents differ from BRINSUPRI?

Joe Schwartz [Senior Managing Director: Great. Thanks so much, and congrats on the very strong performance. It certainly seems like the TAM for BRINSUPRI has a lot of room to expand with a very well-designed strategy to identify patients with COPD or asthma who are exacerbating with bronchiectasis, but might not yet be identified as such. I look forward to hearing about that progress on that front as you embark on this initiative, but I was wondering if you have any plans to develop other DPP1 inhibitors within respiratory disease in order to expand your franchise further, and if so, how do these other agents differ from BRINSUPRI?

Speaker #4: I look forward to hearing about that progress on that front as you embark on this initiative, but I was wondering if you have any plans to develop other DPP-1 inhibitors within respiratory disease in order to expand your franchise further, and if so, how do these other agents differ from Brinsupri?

Speaker #5: Yeah, I appreciate the question. Absolutely, we intend to bring other DPP-1s forward, not just in the respiratory indications, but in others. As an example, 1033 will enter the clinic this year for rheumatoid arthritis and irritable bowel disease a couple of indications within that.

Will Lewis: Yeah, I appreciate the question. Absolutely, we intend to bring other DPP-ones forward, not just in the respiratory indications, but in others. As an example, INS1033 will enter the clinic this year for rheumatoid arthritis and irritable bowel disease, a couple of indications within that, and that'll be in the second half of this year. In parallel, we're also advancing other DPP-ones into conditions in respiratory like, COPD and asthma. That is absolutely on the horizon for us. You know, Martina perhaps can comment a little bit here on the distinction between the patients we're targeting who may be responsive to BRINSUPRI because they are bronchiectasis versus those who are asthmatic and/or COPD of a particular profile, distinct from the bronchiectasis patient, that these other DPP-ones would target. Martina, do you want to address that?

Speaker #5: And that'll be in the second half of this year. In parallel, we're also advancing other DPP-1s into conditions in respiratory like COPD and asthma that is absolutely on the horizon for us.

Speaker #5: Martina, perhaps you can comment a little bit here on the distinction between the patients we're targeting who may be responsive to Brinsupri because they are bronchiectatic, versus those who are asthmatic and/or COPD of a particular profile distinct from the bronchiectasis patient that these other DPP-1s would target?

Speaker #5: Martina, do you want to address that?

Speaker #2: Yes, sure. So we're looking at a phenotype of patients who continue to exacerbate even through their optimally treated for COPD or for asthma already.

Martina Flammer: Yes, sure. So we're looking at a phenotype of patients who continue to exacerbate, even so they are optimally treated for COPD or for asthma already. And most of those patients not only have a higher increase in pulmonary exacerbations, but also an increased acceleration in lung function decline, as well as an increase in mortality. So that is a specific phenotype of patient population that we're looking for.

Speaker #2: And most of those patients not only have a higher increase in pulmonary exacerbations, but also an increased acceleration in lung function decline as well as an increase in mortality.

Speaker #2: So that is a specific phenotype of patient population that we're looking for.

Speaker #3: Your next question comes from Alina of Jason Zemansky from Bank of America. Your line is open.

Operator: Your next question comes from the line of Jason Zimansky from Bank of America. Your line is open.

Operator: Your next question comes from the line of Jason Zemansky from Bank of America. Your line is open.

Speaker #4: Great. Good morning. Congrats on the progress, and thanks so much for taking our question. Will, I was hoping you could provide some additional color regarding the guidance for Brinsupri?

Jason Zemansky: Great, good morning. Congrats on the progress, and thanks so much for taking our question. Well, I was hoping you could provide some additional color regarding the guidance for BRINSUPRI. You know, can you speak to some of the specific elements of patient behavior that gives you confidence at this point, specifically with regards to dynamics like compliance, discontinuations, prescription abandonment? I mean, I know it's early, but do you have a sense of what that looks like, and how did that influence your projections? Thanks.

Jason Zemansky [VP, Equity Research: Great, good morning. Congrats on the progress, and thanks so much for taking our question. Well, I was hoping you could provide some additional color regarding the guidance for BRINSUPRI. You know, can you speak to some of the specific elements of patient behavior that gives you confidence at this point, specifically with regards to dynamics like compliance, discontinuations, prescription abandonment? I mean, I know it's early, but do you have a sense of what that looks like, and how did that influence your projections? Thanks.

Speaker #4: Can you speak to some of the specific elements of patient behavior that gives you confidence at this point, specifically with regards to dynamics like compliance, discontinuations, prescription abandonment?

Speaker #4: I mean, I know it's early, but do you have a sense of what that looks like, and how did that influence your projections? Thanks.

Speaker #5: Sure. So we have, as you might imagine, a number of different data sources we examine, but there is generally a very detailed dashboard. And what I would convey to you is that, across all the metrics, we're seeing at or above our targets.

Will Lewis: Sure. So we have, as you might imagine, a number of different data sources we examine, but there is generally a very detailed dashboard. And what I would convey to you is that across all the metrics we're seeing at or above our targets. And that's very much behind why we have the conviction that we'll do at least $1 billion in revenue in BRINSUPRI this year. So I'd say across the board, we're very encouraged, you know, whether it's market access metrics, whether it's, you know, use, you know, low discontinuation rates, reauthorizations going through. I'd say we feel very, very good about where things are.

Speaker #5: And that's very much behind why we have the conviction that we'll do at least $1 billion in revenue in Brinsupri this year. So, I'd say across the board, we're very encouraged, whether it's market access metrics, whether it's use, low discontinuation rates, reauthorizations going through.

Speaker #5: I’d say we feel very, very good about where things are.

Speaker #3: Your next question comes from a line of Olivia Brayer from Cantor. Your line is open.

Operator: Your next question comes from the line of Olivia Breyer from Cantor. Your line is open.

[Analyst]: Hey, good morning. Thank you for the question, and my congrats as well on the quarter. Can you comment at all on the script trends that Symphony is picking up? Are those January and early February trends indicative of what you guys are seeing on your end? And anything you can tell us at this point, just about how new starts are trending so far this year. And then I did just want to ask around interest in BD activity. It looks like you guys flagged that a couple of times in the slides, and potentially raising capital around that. What kinds of deals are you guys interested in pursuing? And what's the rationale for potentially doing a bigger deal at this point?

Olivia Brayer: Hey, good morning. Thank you for the question, and my congrats as well on the quarter. Can you comment at all on the script trends that Symphony is picking up? Are those January and early February trends indicative of what you guys are seeing on your end? And anything you can tell us at this point, just about how new starts are trending so far this year. And then I did just want to ask around interest in BD activity. It looks like you guys flagged that a couple of times in the slides, and potentially raising capital around that. What kinds of deals are you guys interested in pursuing? And what's the rationale for potentially doing a bigger deal at this point?

Speaker #6: Hey, good morning. Thank you for the question and my congrats as well on the quarter. Can you comment at all on the Scripps trends that Symphony is picking up?

Speaker #6: Are those January and early February trends indicative of what you guys are seeing on your end? And anything you can tell us at this point just about how new starts are trending so far this year?

Speaker #6: And then I did just want to ask around interest in BD activity—it looks like you guys flagged that a couple of times in the slides, and potentially raising capital around that. What kinds of deals are you guys interested in pursuing?

Speaker #6: And what's the rationale for potentially doing a bigger deal at this point?

Speaker #5: Yeah, thanks. As it relates to the performance, I mean, I think things just are very strong out of the gate is the only way I could describe it.

Will Lewis: Yeah, thanks. As it relates to the, to the performance, I mean, I think things just are very strong out of the gate, is the only way I could describe it. And so we, we see, we hear a lot of talk about the Symphony data, obviously. We don't track it, we don't pay attention to it. But, what our- what we were trying to accomplish today, because we are always very detailed and I would say transparent about the puts and takes that may be in operation in any given week for any given medicine. This is what could hold it back. This is what could accelerate it. That, I think, is often interpreted as caution or conservatism on our part.

Speaker #5: And so, we see, we hear a lot of talk about the Symphony data, obviously. We don't track it, we don't pay attention to it.

Speaker #5: But what we were trying to accomplish today—because we are always very detailed, and I would say transparent, about the puts and takes that may be in operation in any given week for any given medicine.

Speaker #5: This is what could hold it back. This is what could accelerate it. That, I think, is often interpreted as caution or conservatism on our part.

Speaker #5: And what I want to make sure we get across today is that we feel great about the way this launch is going. And we do believe we're going to join that very rarest of groups that can produce a billion-plus in revenue by adding quarters two through five together.

Will Lewis: What I want to make sure we get across today is that we feel great about the way this launch is going, and we do believe we're going to join that very rarest of groups that can produce $1 billion+ in revenue by adding Q2 through Q5 together. There aren't many in history that have done it, and those that have, have gone on to be very successful companies. That's because, you know, to get to that level by the end of Q4, you're going to have to be at a run rate that would imply you're going to continue to do very well as you go into 2027 and beyond.

Speaker #5: There aren't many in history that have done it, and those that have have gone on to be very successful companies. And that's because to get to that level by the end of the fourth quarter, you're going to have to be at a run rate that would imply you're going to continue to do very well as you go into '27 and beyond.

Will Lewis: So with all that confidence that comes from doing the examination at a very refined level of script trends, physician behavior, surveys that we do, behavior of patients on medicine, the market access picture, all of these things combine to give us a very good feeling about the direction we're traveling, and that's why we're able, much earlier than expected, to give this direction that we'll do at least $1 billion. That then feeds into the notion that we're on track to get to cash flow positivity without having to access more capital, and that is absolutely the case. The only potential issue we want to raise is that if we see something that's interesting on the business development side, we would not hesitate to bring it on board. We think now is the time to press the advantage should we find-...

Speaker #5: So with all that confidence that comes from doing the examination at a very refined level of Scripps trends, physician behavior, surveys that we do, behavior of patients on medicine, the market access picture, all of these things combined to give us a very good feeling about the direction we're traveling.

Speaker #5: And that's why we're able much earlier than expected to give this direction that we'll do at least a billion. That then feeds into the notion that we're on track to get to cash flow positivity without having to access more capital.

Speaker #5: And that is absolutely the case. The only potential issue we want to raise is that if we see something that's interesting on the business development side, we would not hesitate to bring it on board.

Speaker #5: We think now is the time to press the advantage should we find first or best-in-class compounds that we can bring on board. An example of that would be INS 1148, which we got in our view for a very modest amount and which has what we consider to be DPP-1-like potential in its application across a range of different potential diseases.

Will Lewis: first or best-in-class compounds that we can bring on board. An example of that would be INS1148, which we got, in our view, for a very modest amount, and which has what we consider to be DPP1-like potential in its application across a range of different potential diseases. So more to come on that asset, but assets like that, that we can add that are sort of Phase 2 ready, those are in our sweet spot for sure, where we can step right into the clinic, bring to bear our capabilities in clinical developments and trial design and get to a next candidate molecule that could be first or best in class.

Speaker #5: So, more to come on that asset. But assets like that, that we can add that are sort of Phase 2-ready, those are in our sweet spot for sure.

Speaker #5: Where we can step right into the clinic bring to bear our capabilities in clinical developments and trial design and get to a next candidate molecule that could be first or best in class.

Speaker #3: Your next question comes from a line of Ritu Baral from TD Cowen. Your line is open.

Operator: Your next question comes from the line of Ritu Baral from TD Cowen. Your line is open.

Speaker #6: Good morning, guys. Thanks for taking the question. Will, can I dig into some of this baseline guidance a little further? And Sarah as well.

[Analyst] (TD Cowen): Good morning, guys. Thanks for taking the question. Will, can I dig into some of this baseline guidance a little further, and Sara as well? When will you and when will we get more clarity on refinement of this $1 billion+ level? Because this already sits right around that, and if you stretch the numbers out, it implies, you know, 15% to 20% quarter-over-quarter guidance, which strikes me as relatively modest, given the past few quarters and all of the patient-finding initiatives. Does this have... So can you comment on that? And also, does this idea of requiring the additional paperwork, I guess, and the two or more exacerbations factor into the uptake?

Ritu Baral: Good morning, guys. Thanks for taking the question. Will, can I dig into some of this baseline guidance a little further, and Sara as well? When will you and when will we get more clarity on refinement of this $1 billion+ level? Because this already sits right around that, and if you stretch the numbers out, it implies, you know, 15% to 20% quarter-over-quarter guidance, which strikes me as relatively modest, given the past few quarters and all of the patient-finding initiatives. Does this have... So can you comment on that? And also, does this idea of requiring the additional paperwork, I guess, and the two or more exacerbations factor into the uptake?

Speaker #6: When will you and when will we get more clarity on refinement of this $1 1 billion-plus level? Consensus already sits right around that. And if you stretch the numbers to 20 percent quarter over quarter guidance, which strikes me as a relatively modest given the past few quarters and all of the patient finding initiatives.

Speaker #6: Does this have so can you comment on that and also does this idea of requiring the additional paperwork, I guess, and the two or more exacerbations factor into the uptake?

Speaker #6: Because it sounds like you guys are expecting a certain number of plans to still require this documentation, and that it might be higher than you previously expected.

[Analyst] (TD Cowen): Because it sounds like you guys are expecting a certain number of plans to still require this documentation, and that it might be higher than you previously expected. Thanks. Those were the questions.

Ritu Baral: Because it sounds like you guys are expecting a certain number of plans to still require this documentation, and that it might be higher than you previously expected. Thanks. Those were the questions.

Speaker #6: Thanks. Those were the questions.

Speaker #5: Yeah, so let me be really clear. The market access picture is fantastic from our point of view. It's ahead of where we thought it was going to be internally.

Will Lewis: Yeah. So let me be really clear. The market access picture is fantastic from our point of view. It's ahead of where we thought it was going to be internally. So in no way do I want you to interpret our mentioning of some plans requiring documentation and some not as being indicative of any impact on anything other than enthusiasm for our forecast. What I would tell you about that existence of those requirements of documentation, we always expected that some portion of these plans would require that. That's why we fielded so many field access managers who can support the back office effectively in navigating that. And to be clear, to date, that's how everybody has done it. It's been all medical exception.

Speaker #5: So, in no way do I want you to interpret our mentioning of some plans requiring documentation and some not as being indicative of any impact on anything other than enthusiasm for our forecast.

Speaker #5: What I would tell you about that existence of those requirements of documentation, we always expected that some portion of these plans would require that.

Speaker #5: That's why we fielded so many field access managers who can support the back office effectively in navigating that. And to be clear, to date, that's how everybody has done it.

Speaker #5: It's been all medical exception. So now that the policy's come into place, that smooths the uptake because our concentration has always been on patients with two or more exacerbations, even though our label is for any and all bronchiectatic patients.

Will Lewis: So now that the policies come into place, that smooths the uptake because our concentration has always been on patients with two or more exacerbations, even though our label is for any and all bronchiectasis patients. So strong position with regard to market access and uptake. And with regard to the baseline guidance, look, we have one full quarter under our belt. So it's, I think, audacious to put out a billion-dollar plus forecast for Q2 through Q5, since only 15 products in history have ever done it, to the best of our knowledge, and that includes all the COVID products, the GLP-1s, Harvoni in Hep C, Skyrizi, you know, household name programs. And to that list, Insmed intends to add its name of BRINSUPRI. So we are incredibly happy about where we are and where we're going.

Speaker #5: So, strong position with regard to market access and uptake. And with regard to the baseline guidance—look, we have one full quarter under our belt.

Speaker #5: So it's I think audacious to put out a billion-dollar-plus forecast for quarters two through five since only 15 products in history have ever done it.

Speaker #5: To the best of our knowledge, and that includes all the COVID products, the GLP-1s, Harvoni, and Hep C. Skyrizi. Household name programs. And to that list, InSMED intends to add its name, a Brinsupri.

Speaker #5: So we are incredibly happy about where we are and where we're going. I would not interpret at this stage, which is very early, with one full quarter under our belt, thinking that by saying a billion, we in any way mean to imply that we're slowing down.

Will Lewis: I would not interpret at this stage, which is very early, with one full quarter under our belt, thinking that by saying $1 billion, we in any way mean to imply that we're slowing down. On the contrary, this is what's giving us the confidence to go and suggest that there's going to continue to be acceleration throughout the year. We will provide more qualitative guidance, at least as we go through the year, on how the quarters are progressing. But given the dashboard and the direction we're traveling right now, we feel very good about this launch.

Speaker #5: On the contrary, this is what's giving us the confidence to go and suggest that there's going to continue to be acceleration throughout the year.

Speaker #5: We will provide more qualitative guidance, at least as we go through the year, on how the quarters are progressing. But given the dashboard and the direction we're traveling right now, we feel very good about this launch.

Speaker #3: Your next question comes from a line of Gavin Clark Gartner from Evercore ISI. Your line is open.

Operator: Your next question comes from a line of Gavin Clark-Gartner from Evercore ISI. Your line is open.

Speaker #4: Hey, guys. Thanks for taking the question. So you said you haven't seen any change in approval rates from Startforms to paid drug. What is that actual approval rate right now?

Gavin Clark-Gartner: Hey, guys. Thanks for taking the question. So you said you haven't seen any change in approval rates from Star Forms to Paid Drug. What is that actual approval rate right now? And just on a similar topic, have you seen any changes in the conversion speed from Star Form to Paid Drug? Thank you.

Gavin Clark-Gartner [Managing Director, Equity Research: Hey, guys. Thanks for taking the question. So you said you haven't seen any change in approval rates from Star Forms to Paid Drug. What is that actual approval rate right now? And just on a similar topic, have you seen any changes in the conversion speed from Star Form to Paid Drug? Thank you.

Speaker #4: And just on a similar topic, have you seen any changes in the conversion speed from Startform to paid drug? Thank you.

Speaker #5: Yeah, so we aren't disclosing particular elements of it like the approval rate itself. What I would tell you is that our benchmark internally based off of our experience with Aircase, which was very good, is very high.

Will Lewis: Yeah, so we aren't disclosing particular elements of it, like the approval rate itself. What I would tell you is that our benchmark internally, based off of our experience with ARIKAYCE, which is very good, is very high, and we are at or exceeding that level. And then with regard to any other thing that is actually driving the launch, as I said, the dashboard for us is green. So I don't know how else to convey to you that we feel that we're in a very strong position.

Speaker #5: And we are at or exceeding that level. And then with regard to any other thing that is actually driving the launch, as I said, the dashboard for us is green.

Speaker #5: So I don't know how else to convey to you that we feel that we're in a very strong position.

Speaker #3: Your next question comes from the line of Ellie Merle from Barclays. Your line is open.

Operator: Your next question comes from a line of Ellie Merle from Barclays. Your line is open.

Eliana Merle: Hi, this is Jasmine on for Ellie. Thank you for taking the question and congratulations on the progress. What is the ex-US contribution to your BRINSUPRI guidance of $1 billion or more for 2026? And can you just talk a little bit more about your launch strategy, ex-US, for this year? Thanks.

Jasmine Fels [Associate Equity Research Analyst: Hi, this is Jasmine on for Ellie. Thank you for taking the question and congratulations on the progress. What is the ex-US contribution to your BRINSUPRI guidance of $1 billion or more for 2026? And can you just talk a little bit more about your launch strategy, ex-US, for this year? Thanks.

Speaker #7: Hi, this is Jasmine on for Ellie. Thank you for taking the question and congratulations on the progress. What is the XUS contribution to your Brinsupri guidance of a billion or more for '26?

Speaker #7: And can you just talk a little bit more about your launch strategy XUS for this year? Thanks.

Speaker #5: Sure. So I'll ask Sarah to comment on the different components of our revenue in a moment. The strategy is to launch in Europe and in Japan.

Will Lewis: Sure. So I'll ask Sara to comment on the different components of our revenue in a moment. You know, the strategy is to launch in Europe and in Japan. We want clarity on the MFN policies that are coming forward now. I think we're going to have that in the coming weeks and at the most, months. But until that's clear, it seems to us that the prudent thing to do is to sort of put things on hold until we know what that's going to look like. To be very clear, that does not, you know, reduce our enthusiasm for going to Europe and Japan, and our teams there are continuing to advance work.

Speaker #5: We want clarity on the MFN policies that are coming forward now. I think we're going to have that in the coming weeks and at the most months.

Speaker #5: But until that's clear, it seems to us that the prudent thing to do is to sort of put things on hold until we know what that's going to look like.

Speaker #5: To be very clear, that does not reduce our enthusiasm for going to Europe and Japan. And our teams there are continuing to advance work in contemplation of when that day comes.

Will Lewis: In contemplation of when that day comes, but we really need clarity from the administration first on what these policies are gonna look like, so we can assess those trade-offs and understand where we need to go to. Sara, do you want to take the composition question?

Speaker #5: But we really need clarity from the administration first on what these policies are going to look like. So we can assess those trade-offs and understand where we need to go to.

Speaker #5: Sarah, do you want to take the composition question?

Sara Bonstein: Sure. Happy to. And thanks for the question. What I would comment on is, as we have said previously, any ex-US contribution for BRINSUPRI in 2026 was going to be very, very small, given the original timelines we had put out. We're obviously going to be monitoring the US policy, as Will, as Will stated. So we feel very confident in the $1 billion plus for BRINSUPRI, regardless of sort of the, of the pause, as we're thinking about contributions. And broadly speaking, the contributions for BRINSUPRI will be vastly weighted towards the US.

Speaker #7: Sure, happy to. And thanks for the question. What I would comment on is, as we have said previously, any ex-US contribution for Brinsupri in 2026 was going to be very, very small given the original timelines.

Speaker #7: We had put out we're obviously going to be monitoring the U.S. policy as well, as stated. So we feel very confident in the $1 billion-plus for Brinsupri regardless of sort of the timing of the pause as we're thinking about contributions.

Speaker #7: And broadly speaking, the contributions for Brinsupri will be vastly weighted towards the US.

Operator: Your next question comes from a line of Andy Chen from Wolfe Research. Your line is open.

Speaker #3: Your next question comes from a line of Andy Chen from Wolf Research. Your line is open.

Speaker #8: Hey, this is Brandon on for Andy. And thanks for taking the question. Regarding additional capital to support business development or other value creation, to us, this sounds like incremental spend on clinical programs.

Andy Chen: Hey, this is Brandon calling for Andy, and thanks for taking the question. Regarding additional capital to support business development or other value creation, to us, this sounds like incremental spend on clinical programs. How are you thinking about this relative to achieving cash flow positivity? And is achieving cash flow positivity more of a near-term 2026 goal or in the outer years? Thank you.

Brandon Frith [Associate Equity Research: Hey, this is Brandon calling for Andy, and thanks for taking the question. Regarding additional capital to support business development or other value creation, to us, this sounds like incremental spend on clinical programs. How are you thinking about this relative to achieving cash flow positivity? And is achieving cash flow positivity more of a near-term 2026 goal or in the outer years? Thank you.

Speaker #8: How are you thinking about this relative to achieving cash flow positivity? And is achieving cash flow positivity more of a near-term 2026 goal or in the outer years?

Speaker #8: Thank you.

Speaker #5: Yeah, so I would just say we see a very clear path to cash flow positivity. I view it as an inevitability. Just based on our assumptions about where revenues will go for both Brinsupri and Aircase, our base business that this cash flow positivity journey contemplates includes phase 3 programs for HS, which may or may not happen, as we all know.

Will Lewis: Yeah. So we see a very clear path to cash flow positivity. I, I view it as an inevitability, just based on our assumptions about where revenues will go for both BRINSUPRI and ARIKAYCE. Our base business that this cash flow positivity journey contemplates includes phase 3 programs for HS, which may or may not happen, as we all know. But it contemplates some expenditure in these programs that you're making reference to. So we would put the cash flow positivity journey separate from BD. BD is the thing that is incremental, that would result in us approaching the markets for capital. And, and look, there's plenty of different ways we can do that. And Sara, maybe you want to just take it from here and share your thoughts.

Speaker #5: But it contemplates some expenditure in these programs that you're making reference to. So we would put the cash flow positivity journey separate from BD.

Speaker #5: BD is the thing that is incremental that would result in us approaching the markets for capital. And look, there's plenty of different ways we can do that.

Speaker #5: And Sarah, maybe you want to just take it from here and share your thoughts.

Speaker #7: Sure. Happy to. And thanks for the question. Yeah, as well said, the $1.4 billion provides us that ability to fund through cash flow positivity for our base business, inclusive of the programs that we have under our umbrella today. BD is obviously separate from that.

Sara Bonstein: Sure, happy to, and thanks for the question. Yeah, as Will said, we have the $1.4 billion provides us that ability to fund through cash flow positivity for our base business, inclusive of the programs that we have under our umbrella today. BD is obviously separate from that. As we think about different ways to augment balance sheet, there are, you know, all levers that exist are available to us, and we have the ability to be thoughtful on that, if and when the appropriate BD opportunity did present itself.

Speaker #7: As we think about different ways to augment balance sheet, there are all levers that are. That exist are available to us. And we have the ability to be thoughtful on that if and when the appropriate BD opportunity did present itself.

Speaker #3: Your next question comes from a line of Leonard Tamesha from RBC Capital Markets. Your line is open.

Operator: Your next question comes from the line of Leonid Tameshev from RBC Capital Markets. Your line is open.

Speaker #4: Hey, guys. Thanks for taking my question. I want to ask a little bit about the depth of prescribing. I think you mentioned that a lot of scripts are currently coming from physicians writing just one script.

Leonid Timashev: Hey, guys. Thanks for taking my question. I want to ask a little bit about the depth of prescribing. I think you mentioned that a lot of scripts are currently coming from physicians writing just one script. I guess, is there something that they're waiting for in that initial experience with patients that's, you know, giving them pause from increasing their prescribing right now? Is there any additional education that you guys are doing to sort of try to drive that depth? And I know earlier, at one point, you had mentioned that in some of the academic centers of excellence, the drug's still working its way through ENT committees, I guess. Are you seeing that work its way through? And can we expect an increase in depth of prescribing across, you know, physicians and centers? Thanks.

Speaker #4: I guess, is there something that they're waiting for in that initial experience with patients that's giving them pause from increasing their prescribing right now?

Speaker #4: Is there any additional education that you guys are doing to sort of try to drive that depth? And I know earlier at one point you had mentioned that in some of the centers of academic centers of excellence, the drug's still working its way through ENT committees, I guess.

Speaker #4: Are you seeing that work its way through? I mean, can we expect increase in depth of prescribing across physicians and centers? Thanks.

Speaker #5: Yeah, so this is really important. With almost half having written only one prescription and obviously the vast majority of patients added in the fourth quarter, what we're trying to frame out is that what we've seen is physicians will try with one or two patients and as I just mentioned, fully half of them have only done one.

Will Lewis: Yeah, so this is really important. With almost half having written only one prescription, and obviously, the vast majority of patients added in Q4, you know, what we're trying to frame out is that what we've seen is physicians will try with one or two patients, and as I just mentioned, fully half of them have only done one. So, as those patients experience the use of the drug with, with what has been to date, a benign safety profile and a pretty good, experience that's reported back, we know that that will fuel the, use of the medicine in other patients within those practices. And all of these practices, we think of as having multiple patient candidates, for the drug.

Speaker #5: So as those patients experience the use of the drug with what has been to date, a benign safety profile and a pretty good experience that's reported back, we know that that will fuel the use of the medicine in other patients within those practices.

Speaker #5: And all of these practices we think of as having multiple patient candidates for the drug. Now, if we take a deeper dive on these physicians and their behaviors, it's typical that they would wait a few months for the patient to return to the office to express what their experience has been that dovetails nicely with what we saw as the onset of symptom benefit during the phase three and phase two programs.

Will Lewis: Now, if we take a deeper dive on these physicians and their behaviors, it's typical that they would wait a few months for the patient to return to the office to express what their experience has been. That dovetails nicely with what we saw as the onset of symptom benefit during the phase 3 and phase 2 programs. That gives us some confidence that as we enter Q1 and Q2 of the year, those patients come back in, they report positive experiences. Obviously, that won't be universal, but it has been our experience that it has been very positive. And the consequence of that is those physicians are going to be inclined to write again.

Speaker #5: That gives us some confidence that as we enter the first and second quarter of the year, those patients come back in. They report positive experiences.

Speaker #5: Obviously, that won't be universal, but it has been our experience that it has been very positive. And the consequence of that is those physicians are going to be inclined to write again.

Speaker #5: Of note, we have a very broad prescribing base already. So the ability to gain depth from that positive experience and reinforcement is just one office visit away.

Will Lewis: Of note, we have a very broad prescribing base already, so the ability to gain depth from that positive experience and reinforcement is just one office visit away, and that, to us, is incredibly encouraging as we come into 2026. Yes, we are absolutely drawing attention to that. We now have up and running an extensive speakers bureau, so this is a compliant way of educating people on the experience of the medicine peer-to-peer, and I think that's going to be very beneficial. We have a number of other programs that we activate to make sure that we get, if you will, vocal about what people are seeing, and that allows everyone to understand what the benefits could be and make their own assessment.

Speaker #5: And that to us is incredibly encouraging as we come into 2026. And yes, we are absolutely drawing attention to that. We now have up and running an extensive speakers bureau so this is a compliant way of educating people on the experience of the medicine, peer-to-peer.

Speaker #5: And I think that's going to be very beneficial. We have a number of other programs that we activate to make sure that we get, if you will, vocal about what people are seeing.

Speaker #5: And that allows everyone to understand what the benefits could be and make their own assessment. But I would say universally, their experience to date, we have had a very good feedback loop beginning.

Will Lewis: But I would say universally, their experience to date, we have had a very good feedback loop beginning, and I think that's going to benefit throughout 2026 and beyond.

Speaker #5: And I think that's going to inherit benefit throughout '26 and beyond.

Speaker #3: Your next question comes from a line of Jessica Phi from JPMorgan. Your line is open.

Operator: Your next question comes from the line of Jessica Fai from J.P. Morgan. Your line is open.

Speaker #9: Hey, guys. Good morning. Thanks for taking my question. You talked about the launch being up strong and to the right. Well, I think also in prepared remarks, you noted that quarters can sometimes vary along that strong trend line.

Jessica Fye: Hey, guys. Good morning. Thanks for taking my question. You talked about the launch being up strong and to the right. Well, I think also in prepared remarks, you noted that, you know, quarters can sometimes vary along that strong trend line. And back at J.P. Morgan, you'd kind of flagged some unknowns just related to being so early on in the brensocatib launch. So I'm curious, have any of those unknowns that you alluded to at the start of the year just become more known now that we're at least halfway through the first quarter? And then just quick kind of-

Jessica Fye [Managing Director, Equity Research Analyst: Hey, guys. Good morning. Thanks for taking my question. You talked about the launch being up strong and to the right. Well, I think also in prepared remarks, you noted that, you know, quarters can sometimes vary along that strong trend line. And back at J.P. Morgan, you'd kind of flagged some unknowns just related to being so early on in the brensocatib launch. So I'm curious, have any of those unknowns that you alluded to at the start of the year just become more known now that we're at least halfway through the first quarter? And then just quick kind of-second part to my single question. With revenue guidance now in the picture, should we expect Insmed to continue providing things like patient starts and prescriber metrics going forward? Thank you.

Speaker #9: And back at JPMorgan, you'd kind of flagged some unknowns just related to being so early on in the Brinsupri launch. So I'm curious, have any of those unknowns that you alluded to at the start of the year just become more known now that we're at least halfway through the first quarter?

Speaker #9: And then just a quick kind of second part to my single question: with revenue guidance now in the picture, should we expect Insmed to continue providing things like patient starts and prescriber metrics going forward?

Matt Phipps: ... second part to my single question. With revenue guidance now in the picture, should we expect Insmed to continue providing things like patient starts and prescriber metrics going forward? Thank you.

Speaker #9: Thank you.

Will Lewis: So with regard to the unknowns becoming known, yes. We've seen some things that we weren't aware of and how they would shake out, things that are very important, like market access, policies, the actual experience and timing of getting a prescription filled. Are patients staying on drug or dropping off? Are they getting reauthorizations? Even as they change plans, are those going through? What's the approval rate, whether you have a policy or it's just a medical exception? All of those things, I would say, are trending positive from our internal benchmarks in a way that gives us confidence to be able to provide the guidance we have. And I think as we think about that revenue guidance going forward, we'll obviously provide additional clarity.

Speaker #5: So with regard to the unknowns becoming known, yes, we've seen some things that we weren't aware of and how they would shake out, things that are very important, like market access, policies, the actual experience and timing of getting a prescription filled, our patients staying on drug or dropping off, are they getting reauthorizations, even as they change plans, are those going through?

Speaker #5: What's the approval rate? Whether you have a policy, or it's just a medical exception—all of those things, I would say, are trending positive from our internal benchmarks in a way that gives us confidence to be able to provide the guidance we have.

Speaker #5: And I think as we think about that revenue guidance going forward, we'll obviously provide additional clarity but I think in general, the most important thing we recognize, which is why we put it out today, based on our confidence, is that people want to know what this drug's potential could be, from a revenue-generating point of view.

Will Lewis: I think, you know, in general, the most important thing we recognize, which is why we put it out today based on our confidence, is that people wanna know what this drug's potential could be from a revenue-generating point of view. We see behind each one of those dollars, obviously, a patient that is benefiting from the medicine, and so the revenue is derivative of that patient benefit. It's very important to keep that North Star in mind because ultimately that's what we're in the business of doing, is helping these patients. The positive stories that are coming back from the use and experience with this medicine, we believe, will yield additional revenue benefit, and that's where this revenue guidance is coming from.

Speaker #5: We see behind each one of those dollars, obviously, a patient that is benefiting from the medicine. And so the revenue is derivative of that patient benefit.

Speaker #5: And it's very important to keep that North Star in mind because ultimately that's what we're in the business of doing, is helping these patients and the positive stories that are coming back from the use and experience with this medicine we believe will yield additional revenue benefit.

Speaker #5: And that's where this revenue guidance is coming from. And as those unknowns, that I some of which I reviewed, become clear, it absolutely gives us greater confidence that we're going to be as we say up and to the right.

Will Lewis: And as those unknowns, some of which I reviewed, become clear, it absolutely gives us greater confidence that we're gonna be, as we say, up into the right. It's a little bit hard after only one quarter, full quarter and a partial first quarter, to give a upside, you know, direction in terms of what the cap could be. But I would say we see this as a year of incredible potential, sitting there with at least $1 billion just for BRINSUPRI and $450 to $470 million for ARIKAYCE. That's a very interesting profile where both drugs are first in disease, have no competition for the foreseeable future, and are called on by the same commercial infrastructure.

Speaker #5: It's a little bit hard after only one quarter full quarter and a partial first quarter to give upside direction in terms of what the cap could be.

Speaker #5: But I would say we see this as a year of incredible potential, sitting there with at least $1 billion just for Brinsupri and $450 to $470 million for Aricase. That's a very interesting profile, where both drugs are first in disease, have no competition for the foreseeable future, and are called on by the same commercial infrastructure.

Speaker #5: So there's synergy, there's leverage, there's upside and growth. And when Encore comes out, assuming those results are positive, we have the expansion of that market opportunity.

Will Lewis: So there's synergy, there's leverage, there's upside, and growth, and when ENCORE comes out, assuming those results are positive, we have the expansion of that market opportunity. So, you know, this is just the beginning of this kind of direction and guidance.

Speaker #5: So this is just the beginning of this kind of direction and guidance.

Speaker #3: Your next question comes from a line of Maxwell Skor from Morgan Stanley. Your line is open.

Operator: Your next question comes from the line of Maxwell Score from Morgan Stanley. Your line is open.

Maxwell Skor: Great. Thank you very much for taking my question. So I was just wondering, how do you expect pulmonologists to navigate payer requirements around ruling out COPD or asthma as the primary driver of symptoms? I'm just trying to think about what needs to change in these practices to potentially recognize bronchiectasis as the main driver and maybe a comorbid pop, patient. Thank you.

Speaker #5: Great. Thank you very much for taking my question. So I was just wondering, how do you expect pulmonologists to navigate payer requirements around ruling out COPD or asthma as the primary driver of symptoms?

Maxwell Skor [VP, Equity Research: Great. Thank you very much for taking my question. So I was just wondering, how do you expect pulmonologists to navigate payer requirements around ruling out COPD or asthma as the primary driver of symptoms? I'm just trying to think about what needs to change in these practices to potentially recognize bronchiectasis as the main driver and maybe a comorbid pop, patient. Thank you.

Speaker #5: I'm just trying to think about what needs to change in these practices to potentially recognize bronchiectasis as the main driver, and maybe as a comorbid patient.

Speaker #5: Thank you.

Speaker #4: Sure. So in our phase two and phase three trial, we had about 15 to 20 percent of patients who were comorbid with asthma and COPD.

Will Lewis: Sure. So in our phase 2 and phase 3 trial, we had about 15 to 20% of patients who were comorbid with asthma and COPD. Importantly, particularly if we take something like asthma, it's a spirometry test in the office that enables the diagnosis of COPD. In order to get a definitive diagnosis of bronchiectasis, you need a CT scan and a pulmonologist evaluation. But you're that proximate to that diagnosis. In many cases, CT scans don't get ordered because let's say you were able to diagnose it as bronchiectasis. What good does that do if there's no medicine to treat it? Now there's something that can treat it, that can lower...

Speaker #4: And importantly, particularly if we take something like asthma, it's a spirometry test in the office that enables the diagnosis of COPD. In order to get a definitive diagnosis of bronchiectasis, you need a CT scan and a pulmonologist evaluation.

Speaker #4: But you're that proximate to that diagnosis. In many cases, CT scans don't get ordered because let's say you were able to diagnose it as bronchiectasis.

Speaker #4: What good does that do if there's no medicine to treat it? Now there's something that can treat it that can lower as demonstrated to lower exacerbations and all the other benefits that we've discussed in the past of note at the 25 milligram arm, preservation of lung function, which is particularly relevant for a COPD patient.

Will Lewis: is demonstrated to lower exacerbations and all the other benefits we've received we've discussed in the past, of note at the 25 milligram arm, preservation of lung function, which is particularly relevant for a COPD patient. So these are exciting opportunities for those patients who have bronchiectasis to gain potential benefit from this treatment, and they are literally one CT scan away. So it's not a difficult distinction to make if you do the CT scan, and that's really the funnel change that will have to take place and why we're encouraging physicians to give consideration when they have asthma or COPD patients who are on max treatments and still experiencing exacerbations. "Hey, maybe there's an undiagnosed bronchiectasis patient in front of me." And the numbers that are suggested by the literature are quite substantial here.

Speaker #4: So these are exciting opportunities for those patients who have bronchiectasis to gain potential benefit from this treatment. And they are literally one CT scan away.

Speaker #4: So it's not a difficult distinction to make. If you do the CT scan—and that's really the funnel change—they'll have to take place.

Speaker #4: And why we're encouraging physicians to give consideration when they have asthma or COPD patients who are on max treatments and still experiencing exacerbations—hey, maybe there's an undiagnosed bronchiectatic patient in front of me.

Speaker #4: And the numbers that are suggested by the literature are quite substantial here. So while this may take a little time to turn and activate in terms of a patient population, literally internally, we think of it as another launch it will eventually yield, we think, significant number of patients on label for Brinsupri treatment.

Will Lewis: So while this may take a little time to turn and activate in terms of a patient population, literally internally, we think of it as another launch. It will eventually yield, we think, a significant number of patients on label for BRINSUPRI treatment.

Speaker #3: Your next question comes from Matt Phipps with William Blair. Your line is open.

Operator: Your next question comes from a line of Matt Phipps from William Blair. Your line is open.

Speaker #6: Thanks, David. My question concerns continued execution commercially. In the work that you guys have mentioned that looks at the COPD and bronchiectasis overlap, is there any correlation with ecinophil levels and just given we've had two biologics targeting type 2 inflammation approved for COPD recently, wonder if that just becomes another step for physicians before they order a CT scan as they're thinking about additional pathophysiology for their patients.

Matt Phipps: Thanks for taking my question. Congrats on continued execution commercially. In the work that you guys have mentioned that looks at the COPD and bronchiectasis overlap, is there any correlation with eosinophil levels? And just given, you know, we've had 2 biologics targeting type two inflammation approved for COPD recently, wonder if that just becomes another step for physicians before they order a CT scan as they're thinking about, you know, additional pathophysiology for their patients. Thank you.

Speaker #6: Thank you.

Speaker #4: Sure. And Martina, do you want to field that question?

Will Lewis: Sure. And Martina, do you wanna, do you wanna field that question?

Speaker #7: Yes, sure. So I think if you think about the COPD or the asthma patients, physicians will go with what are their standard of care.

Martina Flammer: Yes, sure. So I think if you, if you think about the COPD or the asthma patients, physicians will go with what are their standard of care and then add medication as patients need it. Many COPD patients or asthma patients have multiple treatments. So for COPD, clearly those are bronchodilators, inhalers, but also LAMA/LABA combinations and of course, corticosteroids. So it depends very much of what is the status of your COPD patients. Are they benefiting it or not? And then you have the opportunity to accelerate into a different treatment paradigm and potentially consider what are biologic treatments and might these patients benefit from them. So there is always a treatment escal treatment paradigm that you look at, depending on what the clinical status is of your patients.

Speaker #7: And then add medication as patients need it. Many COPD patients or asthma patients have multiple treatments. So for COPD, clearly those are bronchodilators, inhalers, but also lavalan combinations.

Speaker #7: And of course, corticosteroids. So it depends very much on what is the status of your COPD patients. Are they benefiting it or not? And then you have the opportunity to accelerate into a different treatment paradigm and potentially consider what are biologic treatments and may these patients benefit from them.

Speaker #7: So there is always a treatment paradigm that you look at from depending on what the clinical status is of your patients. But you have to have as a physician also the clinical suspicion that it may not only be the underlying disease that you're treating.

Martina Flammer: But you have to have, as a physician, also the clinical suspicion that it may not only be the underlying disease that you're treating. So the COPD and/or the asthma that you're treating, but if your patient is becoming optimally treated, even if this is a biologic and continues to exacerbate, then the question has to be raised of, is that what's driving an exacerbation? Not really COPD or asthma. They may still have that, and you're treating that optimally, but then you're asking, now I have to see if there is something else, and that is where the question comes in: Have I run a CT scan? And I think often patients, if you add additional medications along that treatment paradigm, physicians will ask themselves the question, what else do I have to look for before I continue escalating a treatment paradigm?

Speaker #7: So the COPD or the asthma that you're treating, but if your patient is becoming optimally treated, even if this is a biologic and continues to exacerbate, then the question has to be raised of is that what's driving an exacerbation?

Speaker #7: Not really COPD or asthma. They may still have that and you're treating that optimally, but then you're asking now I have to see if there is something else.

Speaker #7: And that is where the question comes in. Have I run a CT scan? And I think often patients if you add additional medications along that treatment paradigm, physicians will ask themselves the question, what else do I have to look for before I continue escalating a treatment paradigm?

Speaker #3: Your next question comes from a line of Danielle Brill from Truist. Your line is open.

Operator: Your next question comes from a line of Danielle Brill from Truist. Your line is open.

Speaker #8: Hey, guys. This is Alex on for Danielle. Thanks for taking the question. I was curious if you could give a little bit of a breakdown of the payers that are requiring documentation versus attestation versus the plans that require medical exception.

Danielle Brill: Hey, guys, this is Alex on for Danielle. Thanks for taking the question. I was curious if you could give a little bit of a breakdown of the payers that are requiring documentation versus attestation, versus the plans that require medical exception, and what percentage of covered lives does that represent? And then lastly, just if you could share your confidence in getting policies in place that are currently using medical exemption going forward. Thanks so much.

Alex Xenakis: Hey, guys, this is Alex on for Danielle. Thanks for taking the question. I was curious if you could give a little bit of a breakdown of the payers that are requiring documentation versus attestation, versus the plans that require medical exception, and what percentage of covered lives does that represent? And then lastly, just if you could share your confidence in getting policies in place that are currently using medical exemption going forward. Thanks so much.

Speaker #8: And what percentage of covered lives does that represent? And then lastly, just if you could share your confidence in getting policies in place that are currently using medical exemption going forward.

Speaker #8: Thanks so much.

Speaker #4: Yeah. So Alex, I'm going to disappoint you. I'm not going to break out the covered lives and what is documentation, what is not. I would just tell you this, which is the benchmarks we set for what percentage would be required documentation.

Will Lewis: Yeah. So Alex, I'm gonna disappoint you. I'm not gonna break out the covered lives and what is documentation, what is not. I would just tell you this, which is the benchmarks we set for what percentage would be, you know, require documentation. They're right in line, we're probably a little better than what we were thinking. And I think what's important is that all of the guidance that's coming out, that we've seen so far, is aligned with the guidance that came out at Chest, which is that the patients you wanna, you wanna be thinking of first for this, are two or more exacerbations, and that's the way that the market access world is interpreting it. It's the way we've driven physicians to think about the use of this drug in terms of first patients to try it on.

Speaker #4: They're right in line. We're probably a little better than what we were thinking. And I think what's important is that all of the guidance that's coming out that we've seen so far is aligned with the guidance that came out at CHEST, which is that the patients you want to be thinking of first for this are two or more exacerbations.

Speaker #4: And that's the way that the market access world is interpreting it. It's the way we've driven physicians to think about the use of this drug in terms of first patients to try it on.

Speaker #4: And so I think all of that aligns nicely. And so what you've seen in the partial third quarter and first full quarter and the fourth quarter is this market access picture that is not expected to change dramatically in terms of our ability to add patients without a lot of friction.

Will Lewis: And so I think all of that aligns nicely. And so what you've seen in the partial Q3 and first full quarter in the Q4, is this market access picture that is not expected to change dramatically in terms of our ability to add patients, without a lot of friction. And that's because, not only are we very experienced with the market medical exception pathway, but we are getting many plans to agree to doing attestation, which should, if anything, help the process. The more predictable it becomes, the easier it is for the back office to know what to do, and our teams are there in a compliant way to support that education and execution. So I feel very good about the market access picture.

Speaker #4: And that's because not only are we very experienced with the market medical exception pathway, but we are getting many plans to agree to doing attestation, which should, if anything, help the process.

Speaker #4: The more predictable it becomes, the easier it is for the back office to know what to do. And our teams are there in a compliant way to support that education and execution.

Speaker #4: So I feel very good about the market access picture. I think within the launch, when we look back at this and talk about what has gone very well, market access is going to be one component that we got right.

Will Lewis: I think within the launch, when we look back at this and talk about what has gone very well, market access is gonna be one component, that we got right.

Speaker #3: Your next question comes from a line of Adam Walsh from Roth Capital. Your line is open. Adam, your line is open. Your next question comes from a line of Steven Willie from Stifel.

Operator: Your next question comes from the line of Adam Walsh from Roth Capital. Your line is open. Adam, your line is open. Your next question comes from the line of Steven Willey from Stifel. Your line is open.

Speaker #3: Your line is open.

Speaker #8: Yeah, good morning. Thanks for taking the question. Just curious if you're expecting the majority of patient reauthorizations to occur six months after starting therapy.

Stephen D. Willey: Yeah, good morning. Thanks for taking the question. Just curious if you're expecting the majority of patient reauthorizations to occur six months after starting therapy. And I know your comments seem to suggest that some payers have already required reauthorization at earlier time points. So just curious if there's anything that you can say about the seamlessness of the reauthorization experience you've seen thus far. Thanks.

Stephen Willey [Managing Director, Equity Research: Yeah, good morning. Thanks for taking the question. Just curious if you're expecting the majority of patient reauthorizations to occur six months after starting therapy. And I know your comments seem to suggest that some payers have already required reauthorization at earlier time points. So just curious if there's anything that you can say about the seamlessness of the reauthorization experience you've seen thus far. Thanks.

Speaker #8: And I know your comments seem to suggest that some payers have already required reauthorization at earlier time points. So, just curious if there's anything that you can say about the seamlessness of the reauthorization experience you've seen thus far.

Speaker #8: Thanks.

Speaker #4: Yeah, the point of greatest friction, I think, in this world is when you get into the first quarter, and you have some patients who change medical plans.

Will Lewis: Yeah. The point of greatest friction, I think, in this world, is when you get into the Q1 and you have some patients who change medical plans; does that get bridged effectively? Is the reset of the copay, you know, what kind of a break does that put on things? And I would say that, you know, in our Q1, we feel very good about the way things have gone, so much so that we can give the guidance that we provided. I don't know that we can give a lot more detail, beyond that, except to say that, you know, if we were seeing difficulty or breaks of some kind, we would be calling that out, and we're just, we're not.

Speaker #4: Does that get bridged effectively? Is the reset of the copay—what kind of a break does that put on things? And I would say that in our first quarter, we feel very good about the way things have gone.

Speaker #4: So provided. I don't know that we can give a lot more detail beyond that except to say that if we were seeing difficulty or breaks of some kind, we would be calling that out.

Speaker #4: And we're not.

Speaker #3: Your next question comes from a line of Greg Savanage from Mizuho. Your line is open.

Operator: Your next question comes from a line of Greg Svanidjev from Mizuho. Your line is open.

Martina Flammer: Thanks. Good morning. Congrats on the quarter, and thanks for taking my questions. I really want to tap into the additional BRINSUPRI opportunity and the 32 million or so patients who have COPD and asthma as a potential revenue opportunity. Just to clarify, to be able to tap into that patient population, is there anything that you need to do? i.e., do you need to run a clinical study, or how would that mechanically work to be able for a doctor to prescribe that medicine? Would that be off-label, or just any color there, please?

Speaker #8: Thanks. Good morning. Congrats on the quarter and thanks for taking my questions. I really want to tap into the additional Brin Supri opportunity in the 32 million or so patients who have COPD and asthma as a potential revenue opportunity just to clarify to be able to tap into that patient population?

Graig Suvannavejh [Managing Director, Senior Equity Research Analyst: Thanks. Good morning. Congrats on the quarter, and thanks for taking my questions. I really want to tap into the additional BRINSUPRI opportunity and the 32 million or so patients who have COPD and asthma as a potential revenue opportunity. Just to clarify, to be able to tap into that patient population, is there anything that you need to do? i.e., do you need to run a clinical study, or how would that mechanically work to be able for a doctor to prescribe that medicine? Would that be off-label, or just any color there, please?

Speaker #8: Is there anything that you need to do, i.e., do you need to run a clinical study or how would that mechanically work to be able for a doctor to prescribe that medicine?

Speaker #8: Would that be off-label or just any color there, please?

Speaker #4: Yeah, I know. So we're speaking very specifically on label exclusively. And that's all we would ever focus on. And the way that flow occurs is for a physician who has as Martina described either asthma or COPD, perhaps is fully treated for that condition, and yet continues to exacerbate.

Will Lewis: Yeah, I know. So we're speaking very specifically on label exclusively, and that's all we would ever focus on. And the way that flow occurs is for a physician who has, as Martina described, either asthma or COPD, perhaps is fully treated for that condition and yet continues to exacerbate and perhaps have sputum, expectoration. That patient becomes potentially a candidate for a CT scan to evaluate if the additional difficulties they're experiencing are a byproduct of bronchiectasis. The moment that CT scan and pulmonologist have a definitive diagnosis of bronchiectasis, they are on label for our drug. If they have had two or more exacerbations, their path to reimbursement for the use of the medicine should be very smooth.... And so, that's really what we're describing, is that all of the COPD and asthma patients, 32 million, we estimate, is the number.

Speaker #4: And perhaps have sputum expectoration. That patient becomes potentially a candidate for a CT scan to evaluate if the additional difficulties they're experiencing are a byproduct of bronchiectasis.

Speaker #4: The moment that CT scan and pulmonologist have a definitive diagnosis of bronchiectasis, they are on label for our drug. If they have had two or more exacerbations, their path to reimbursement for the use of the medicine should be very smooth.

Speaker #4: And so that's really what we're describing is that all of the COPD and asthma patients 32 million, we estimate is the number. What percentage of those may still be experiencing exacerbations despite best treatment?

Will Lewis: What percentage of those may still be experiencing exacerbations despite best treatments? And then of those, how many have either already had a CT scan, and so we can go back and review those CT scans to see if there's evidence of bronchiectasis. Because remember, if you do a CT scan, and it's not that uncommon for many of these patients to have one, it doesn't mean that they would have identified bronchiectasis. They have to go looking for it, or perhaps the radiologist called it out, but it doesn't get coded because back then there was nothing approved to treat it. So there is advantage in going back and looking at existing CT scans and doing a definitive assessment of whether there's bronchiectasis in evidence.

Speaker #4: And then, of those, how many have either already had a CT scan? And so we can go back and review those CT scans to see if there's evidence of bronchiectasis.

Speaker #4: Because remember, if you do a CT scan and it's not that uncommon for many of these patients to have one, it doesn't mean that they would have identified bronchiectasis.

Speaker #4: They have to go looking for it. Or perhaps the radiologist called it out, but it doesn't get coded because back then there was nothing approved to treat it.

Speaker #4: So there is advantage in going back and looking at existing CT scans and doing a definitive assessment of whether there's bronchiectasis in evidence. And there's also the patients that are having the experiences I'm describing getting an additional CT scan for the first time and having it evaluated at that moment.

Will Lewis: And there's also the patients that are having the experiences I'm describing, getting an additional CT scan for the first time and having it evaluated at that moment. So our education efforts are both medical and through commercial channels, compliantly raising the index of suspicion about this and hopefully identifying those patients who would benefit with a definitive diagnosis of bronchiectasis and getting them on BRINSUPRI.

Speaker #4: So our education efforts are both medical and through commercial channels compliantly raising the index of suspicion about this and hopefully identifying those patients who would benefit with a definitive diagnosis of bronchiectasis and getting them on Brin Supri.

Speaker #3: Your next question comes from a line of Ash Verma from UBS. Your line is open.

Operator: Your next question comes from a line of Ash Verma from UBS. Your line is open.

Ashwani Verma: Morning, this is Paritosh on for Ash. A question on the TPIP IPF study design. How critical do you think it is for you to show survival benefit, to claim a major contribution to patient care versus Tyvaso? And does your potential study design change based on what Tyvaso shows on the survival endpoint in the TETON-1 study that's about to read out? Thanks.

Paritosh Gangaramani: Morning, this is Paritosh on for Ash. A question on the TPIP IPF study design. How critical do you think it is for you to show survival benefit, to claim a major contribution to patient care versus Tyvaso? And does your potential study design change based on what Tyvaso shows on the survival endpoint in the TETON-1 study that's about to read out? Thanks.

Speaker #9: Morning. This is Barry Josh on for Ash. A question on the DPIP/IPF study design. How critical do you think it is for you to show survival benefit to claim a major contribution to patient care versus Diverso?

Speaker #9: And does your potential study design change based on what Diverso shows on the survival endpoint in the DON1 study that's about to read out?

Speaker #9: Thanks.

Will Lewis: Yeah. So what I would say is that that study design is not yet finalized. I don't know if, Martina, you want to comment on anything further with regard to where we're going with that, with that TPIP program and IPF, and particularly the survival endpoint he was raising.

Speaker #4: Yeah. So what I would say is that that study design is not yet finalized. I don't know if Martina, you want to comment on anything further with regard to where we're going with that DPIP program and IPF?

Speaker #4: And particularly the survival endpoint he was raising.

Speaker #10: Yeah. So we haven't really looked at exactly what that design will be. I think looking at Teton and what endpoints they use and also the design is a good guidance.

Martina Flammer: Yeah. So we haven't really looked at exactly what that, what the design will be. I think looking at Teton and what endpoints to use and also the design is a good guidance. Certainly, that will be one of one considerations for us, but we have not at that point, really communicated on the design. But we'll discuss that also with the FDA, and then we'll share it with you, once we have a better picture of what we will move forward with.

Speaker #10: Certainly, that will be one consideration for us. But we have not, at that point, really communicated on the design. But we'll discuss that also with the FDA and then we'll share it with you once we have a better picture of what we will move forward with.

Speaker #3: Your next question comes from a line of Ben Burnett from Wells Fargo. Your line is open.

Operator: Your next question comes from a line of Ben Burnett from Wells Fargo. Your line is open.

Tiago Fauth: Hi, this is Jin Shi on for Ben. So, thanks for taking our questions. Two quick ones. First one, just want to make sure I understand correctly. So the $1 billion guidance is all, two pulmonary, pulmonary exacerbation patients, and any one PE patients is going to be, upside. And second one on ARIKAYCE. Data is around the corner. Any commentary that you can provide on, blinded data, whether it's PRO or sputum conversion rate? And what is... kind of internally, how do you think about a bar for, approval and most importantly, commercial, success? Thanks for that. Thanks for your time.

Tiago Fauth [Director, Equity Research: Hi, this is Jin Shi on for Ben. So, thanks for taking our questions. Two quick ones. First one, just want to make sure I understand correctly. So the $1 billion guidance is all, two pulmonary, pulmonary exacerbation patients, and any one PE patients is going to be, upside. And second one on ARIKAYCE. Data is around the corner. Any commentary that you can provide on, blinded data, whether it's PRO or sputum conversion rate? And what is... kind of internally, how do you think about a bar for, approval and most importantly, commercial, success? Thanks for that. Thanks for your time.

Speaker #11: Hi. This is Tien Chi on for Ben. So thank you for taking our questions. Two quick ones. First one, just want to make sure I understand correctly.

Speaker #11: So, the $1 billion guidance is all to pulmonary exacerbation patients, and any 1-PE patients is going to be upside. And, second, on our case, data is around the corner.

Speaker #11: Any commentary that you can provide on blinded data? Was it PRO or sputum conversion rate? And what is kind of internally, how do you think about a bar for approval and most importantly, commercial success?

Speaker #11: Thanks for your time.

Speaker #4: Sure. So on the billion-dollar question, are they all is that revenue guidance, is that based off patients who have two or more exacerbations? Yes, is the answer to that.

Will Lewis: Sure. So on the billion-dollar question, are they all, you know, is that, that revenue guidance, is that based off patients who have 2 or more exacerbations? Yes, is the answer to that. We think there is upside from the additional 250,000 patients. This is a progressive disease, and we do anticipate, as the most recent paper I mentioned in the remarks, identifies that some of those patients with less than 2 or more exacerbations will fall into 2 or more exacerbations as time goes on, because of the progressive nature of the disease and the heightened awareness of diagnosis and all the rest. In response to your second question, you'll be pleased to know we've decided we're not going to be getting into the game of blended blinded data anymore. We certainly monitor that.

Speaker #4: We think there is upside from the additional 250,000 patients. This is a progressive disease and we do anticipate, as the most recent paper I mentioned in the remarks, identifies that some of those patients with less than two or more exacerbations will fall into two or more exacerbations as time goes on because of the progressive nature of the disease and the heightened awareness of diagnosis and all the rest.

Speaker #4: In response to your second question, you'll be pleased to know we've decided we're not going to be getting into the game of blended, blinded data anymore.

Speaker #4: We certainly monitor that. I think the challenge of it is always knowing that there is an alternate explanation for whatever promising direction it may be suggesting.

Will Lewis: I think the challenge of it is always, knowing that there is an alternate explanation for whatever promising direction it may be suggesting. Where I feel confident in the ARIKAYCE ENCORE readout is that we've already run multiple studies using this drug in this disease and have seen the primary endpoint and secondary endpoints measured with success on more than one occasion. The exception to that, obviously, is the newly developed PRO, but that PRO was developed in conjunction with the FDA, using the ARISE data as the benchmark for understanding what we think is likely to be the way to interpret clinical relevance. And what does that mean? It means that we feel very good going into the discussion with FDA, that the results will be compelling enough to enable a full approval for all MAC NTM. In Japan, all they want is culture conversion.

Speaker #4: Where I feel confident in the error case Encore readout is that we've already run multiple studies using this drug in this disease and have seen the primary endpoint and secondary endpoints measured with success on more than one occasion.

Speaker #4: The exception of that obviously is the newly developed PRO, but that PRO was developed in conjunction with the FDA using the arise data as the benchmark for understanding what we think is likely to be the way to interpret clinical relevance.

Speaker #4: And what does that mean? It means that we feel very good going into the discussion with FDA that the results will be compelling enough to enable a full approval for all MAC NTM.

Speaker #4: In Japan, all they want is culture conversion. Obviously, it has to be safe and effective. But they measure effectiveness by culture conversion. And that's the primary endpoint.

Will Lewis: Obviously, it has to be safe and effective, but they measure effectiveness by culture conversion, and that's the primary endpoint. We've never had a trial where we have not definitively won on that front. To remind you, the ARISE trial was basically a six-month trial with one month off, and the ENCORE trial is simply a longer version of that same trial design. We recruited the patients at the same time. We simply randomized more of them to the shorter-term ARISE trial. And so for all of these reasons, we feel very good about ENCORE being producing data that will enable approval in the US and Japan.

Speaker #4: And we've never had a trial where we have not definitively won on that front. To remind you, the arise trial was basically a six-month trial with one-month off and the encore trial is simply a longer version of that same trial design.

Speaker #4: We recruited the patients at the same time. We simply randomized more of them to the shorter-term arise trial. And so for all of these reasons, we feel very good about encore.

Speaker #4: Being producing data that will enable approval in the US and Japan. We obviously have to see the data to make final conclusions, but that's right around the corner.

Will Lewis: We obviously have to see the data to make final conclusions, but that's right around the corner, and it will unlock a very substantial additional population for ARIKAYCE, going from roughly 30,000 addressable patients to over 200,000. So this is a very substantial future contributor starting in 2027, assuming that these data are what we expect them to be, and then we're able to launch in the US and in Japan.

Speaker #4: And it will unlock a very substantial additional population for error case going from roughly 30,000 addressable patients to over 200,000. So this is a very substantial future contributor starting in 207, assuming that these data are what we expect them to be.

Speaker #4: And then we're able to launch in the US and in Japan.

Speaker #3: Your final question comes from the line of Adam Walsh from Roth Capital. Your line is open.

Operator: Your final question comes from a line of Adam Walsh from Roth Capital. Your line is open.

Speaker #11: Great. Thanks for taking my question. Good morning. My question's on Brin Supri persistence. We recently talked to a pulmonologist who likened Brin Supri to sort of a blood pressure pill and that it prevents long-term damage but doesn't deliver necessarily immediate symptomatic relief.

Adam Walsh: ... Great. Thanks for taking my question. Good morning. My question's on BRINSUPRI persistence. We recently talked to a pulmonologist who likened BRINSUPRI to sort of a blood pressure pill, and that it prevents long-term damage, but doesn't deliver necessarily immediate symptomatic relief. And he flagged the one-year mark as the key discontinuation risk based on his biologic experience. With your earliest patients now approaching six months on therapy, can you share any aggregate persistence or refill data and talk to your strategy about ensuring persistence with the medicine? Thank you.

Adam Walsh: Great. Thanks for taking my question. Good morning. My question's on BRINSUPRI persistence. We recently talked to a pulmonologist who likened BRINSUPRI to sort of a blood pressure pill, and that it prevents long-term damage, but doesn't deliver necessarily immediate symptomatic relief. And he flagged the one-year mark as the key discontinuation risk based on his biologic experience. With your earliest patients now approaching six months on therapy, can you share any aggregate persistence or refill data and talk to your strategy about ensuring persistence with the medicine? Thank you.

Speaker #11: Any flag the one-year mark as the key discontinuation risk based on his biologic experience? With your earliest patients now approaching six months on therapy, can you share any aggregate persistence or refill data and talk to your strategy about ensuring persistence with the medicine?

Speaker #11: Thank you.

Speaker #4: Yeah. So the first thing I would say is that refills so far are going very well. So I think that that's a very positive sign early on.

Will Lewis: Yeah. So the first thing I would say is that refills so far are going very well. So I, I think that that's a very positive sign early on. We know that what is great about this medicine as was once described by someone at one of the faculty at ATS, who described it as the holy grail of pulmonary medicine because it was the last unaddressed patient population, and the treatment burden of a once-a-day pill is unbelievably low relative to what these people typically take for other indications in the respiratory arena, or otherwise. It's often inhaled medicines, as you know, and those kinds of treatments. As we think about where we go from here, I would tell you that that profile, that dynamic, should inure benefit to the uptake of the medicine.

Speaker #4: We know that what is great about this medicine, as was once described by someone at one of the faculty at ATS, who described it as the holy grail of pulmonary medicine because it was the last unaddressed patient population, and the treatment burden of a once-a-day pill is unbelievably low relative to what these people typically take for other indications in the respiratory arena.

Speaker #4: Or otherwise. It's often inhaled medicines, as you know, and those kinds of treatments. As we think about where we go from here, I would tell you that that profile, that dynamic should inherently benefit to the uptake of the medicine.

Speaker #4: We know from the secondary endpoints in the phase three study, especially at the 25 milligram dose, these patients had a highly nominally statistically significant finding in favor of feeling better on the medicine.

Will Lewis: We know from the secondary endpoints in the Phase 3 study, especially at the 25mg dose, these patients had a highly nominally statistically significant finding in favor of feeling better on the medicine. So it's our expectation that that storyline will come back and empower physicians to write additional prescriptions. And through that process, we would expect things to grow and expand as our depth increases. I don't worry so much about the continuation of the use of the drug, given some of the early stories we've heard about patients feeling better on the drug. But even without that, knowing the avoidance of losing lung function, which many of these patients are focused on, at the 25mg dose, we were statistically significant in preserving lung function.

Speaker #4: So it's our expectation that that storyline will come back and empower physicians to write additional prescriptions. And through that process, we would expect things to grow and expand as our depth increases.

Speaker #4: I don't worry so much about the continuation of the use of the drug given some of the early stories we've heard about patients feeling better on the drug.

Speaker #4: But even without that, knowing the avoidance of losing lung function, which many of these patients are focused on at the 25 milligram dose, we were statistically significant in preserving lung function.

Speaker #4: So even if you don't feel it, to be told that by your physician, I think, is a very compelling driver for use. And certainly, the refill rate would suggest that.

Will Lewis: So even if you don't feel it, to be told that by your physician, I think, is a very compelling driver for use, and certainly the refill rate would suggest that.

Operator: This concludes today's conference call. We thank you for your participation, and you may now disconnect.

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