Insmed Incorporated

Thank you for standing by and welcome to the Innsmed 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 Brian Dunn, head of investor relations. You may begin.

Thank you, Rob. Good day everyone and welcome to today's conference call to discuss Inns Med's fourth quarter 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 Sarah Bonstein, Chief Financial Officer. After their comments, they will be joined by Martina Flammer, Chief Medical Officer, for the Q&A session. I will now turn the call over to Will.

Thank you, Brian. Good morning, everyone, and thank you for joining us. 2025 was an exceptional year for InsumEd, 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 Ericase, 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 CRS without nasal polyps program last quarter. We entered 2026 with momentum that positions Insmed for sustained leadership in both bronchiectasis and MTM. In the year ahead, we intend to accelerate and expand the U.S. launch of Brinsupre while continuing to grow Aracase. 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. 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. Coupled with another expected strong year of performance from Aircase, 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. In 2025, the U.S. 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 Brinsupre has the potential to be among the best, if not the best, specialty respiratory launch ever. Let me now take a moment to illustrate where we expect the Brinsupre opportunity to evolve over time. In these early months of the launch, we see Brinsupre 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 U.S. based on Bransupri's label as 500,000 currently diagnosed patients with non-CF bronchiectasis. 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 Brinsupre 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. 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 the 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 studied patients had two or more exacerbations in either the first or second year. Based on that study, it is our expectation that patients will continue to move into the 2-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 U.S. 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. The potential additional patients from these populations, which would be on label for brinsupre 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. 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. 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. 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 have prescribed bursupre 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. 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. 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 Brinsupre. A critical element of successful launches is favorable pair access dynamics, and I am pleased to say that this is progressing very well. In fact, over 90% of targeted patient lives have access to GetFriendSupre 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 Aircase, which even now is primarily reimbursed through medical exception, we've become skilled at providing education to health care providers and their offices about documentation and process requirements. 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 Brinsupre. I am pleased to say 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. In summary, the Brinsupri launch continues to be very strong. The rate of patient ads, 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 clear picture of how big and when those additional patients may be diagnosed and become unlabeled 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 error case. 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 Aircase's global revenues. In Europe, Aircase grew even faster, albeit from a more modest revenue base. This strong commercial execution sets the stage for Aircase's next clinical readout, the Phase III Encore Trial, which we expect to announce in March or April of this year. success in ENCOR could open an opportunity to increase the addressable market for error case 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 III clinical programs in parallel. 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 tryprosinopalmitil 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 proprostanil and by means of a major contribution to patient care compared to the approved subcutaneous and intravenous formulation of proprostanil, close quote. 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 proprosenal options. In our view, this supports our long-held conviction that TPIP could become the prosenoid of choice for physicians and patients. Last month, we presented the trial design for our PALM PAH Phase III 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 II results, that we would need just one phase three trial powered at the standard .05 alpha for a registrational submission. On this slide, you can see a depiction of the trial design for PALMPAH. While much of the design is similar to our phase two trial, there are some key differences. 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 II. 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 proprostanil. That is more than three times the highest labeled daily dose of Tyveso DPI for patients that fully comply with the four doses required per day with that treatment. Another difference is that the Phase III study will allow patients to be on background cetatercept. 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 one to three hours post-dose to approximate TPIP's peak effect, similar to trials of other proprosenol products. Trough 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 Brinsupre launch continues to go well, allowing us to announce revenue guidance for 2026 of at least a billion dollars for that therapy. When combined with the strong performance that we expect for EraCase in 2026, we expect to produce revenue on a company-wide basis that more than doubles from last year. And even that could be just the beginning, as we await a near-term pivotal readout for error case that could expand its label, and we work to identify new patients who could benefit from Brinsupre. For TPIP, we have received an orphan drug designation for tryprosinopalmitil for the treatment of PAH, and have released a 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 Sarah.