Insmed Incorporated

Thank you for standing by. My name is Pam, and I will be your conference operator today. At this time, I would like to welcome everyone to the INSMED fourth quarter and full year 2024 financial results 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'd 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, press star 1 again. Thank you. I would now like to turn the conference over to Brian Dunn. You may begin.

Thank you, Pam. Good day, everyone, and welcome to today's conference call where we will discuss InnsMed's fourth quarter and full year 2024 financial results and provide a business update. I am joined today by Will Lewis, Chair and Chief Executive Officer, and Sarah Bonstein, Chief Financial Officer, who will each provide prepared remarks after which they will be joined by Martina Flammer, Chief Medical Officer, for the Q&A session. Before we start, please note that today's call will include forward-looking statements based on our current expectations. These statements represent our judgment as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. Please refer to our filings with the Securities and Exchange Commission for more information concerning the risk factors that could affect the company. 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 a prescribing decision. I will now turn the call over to Will for prepared remarks.

Thank you, Brian, and welcome everyone. 2024 was an historic year for Incemed. While we celebrated the outcome of one major clinical trial, we also remained focused on laying the foundation for continued success in 2025 and beyond. We believe we are just at the beginning of the realization of more than a decade's worth of work that has put us in a position to have several clinical and commercial catalysts, all hitting major inflection points in quick succession. At the heart of our accomplishments in 2024 was the impressive phase three data from the Aspen study for brenzocatab and bronchiectasis. Historically, when a company has validated a new mechanism of action with the potential to address significant unmet needs across multiple indications, this accomplishment has resulted in meaningful patient benefit and consequent value creation, sometimes in the tens of billions of dollars or more. Often, the phase three readout is just the beginning of the value creation curve. We believe this could be the case for Brenzocatib, with the Aspen readout representing just the beginning of the future potential for DPP-1 inhibition. Aspen's success was only part of what made 2024 special. We also welcomed the first data from TPIP in PHILD, which began to reveal this compound's potential as a best-in-class treatment for pulmonary hypertension. We also drove steady enrollment across our ongoing mid- to late-stage trials for EraCase, Brenzocatib, and TPIP, all of which remain on track or ahead of schedule for readout. Meanwhile, EraCase quietly and steadily produced the most impressive performance in its six-year commercial history, with record-setting revenues that came in higher than even our own internal projections. Finally, in 2024, we took actions to deliberately strengthen our balance sheet, positioning Insomed for success as we accelerate into the year ahead. In 2025, the expected U.S. launch of Brenzocatib and bronchiectasis in the third quarter is going to take center stage. But you can also expect Phase II data for TPIP and PAH in the middle of the year and Phase II data for Brenzocatib and CRS without nasal polyps, which we estimate will read out by the end of the year. It is worth noting that this string of significant clinical and commercial catalyst does not end in 2025. In the first quarter of 2026, we expect our phase three encore trial for error case to read out, holding the potential to expand our label to include all patients with a MAC lung infection. Also in 2026, we expect to share updates from our phase two trial of brenzocatib and hydradenitis supertiva. from several of our gene therapies, including DMD, ALS, and Stargardt disease, and from our next generation DPP-1 programs, all while we launch RENSOcadab in Europe, the UK, and Japan, assuming we secure approvals in those territories. I believe that our ability to execute on the many opportunities ahead will solidify in Smith's place among a small group of industry peers that have pioneered an entirely new mechanism of action while successfully advancing other programs in parallel. Now let me walk you through the progress we are making in pursuit of this ambition, starting with brenzocatib. Earlier this month, we announced that the NDA filing for brenzocatib and bronchiectasis was accepted by the FDA under priority review with a PDUFA date of August 12, 2025. We are thrilled to be one step closer to bringing this important therapy to patients who have waited a long time for such a breakthrough. As of today, the FDA has not yet indicated whether it will convene an advisory committee as part of its review process. The FDA can make that choice at any time during the priority review. Should they call for one, we will work to accommodate whatever topics the FDA may wish to explore. As we learn more about any potential outcome, we will share that information. Now that we know the likely timing for the FDA's decision, I'd like to spend a few moments revisiting our expectations for Brenzocatab's launch. Previously, we provided analogs of strong respiratory launches that we aspire to emulate with Brenzocatib, including Dupixent, Fastenra, Ofev, and Taspire. On average, these products recorded combined revenues for the first two quarters of launch in the high double-digit millions. But note that most of these products benefited from approval dates that enabled their first quarter of reported sales to include nearly a full quarter. In contrast, With a potential approval and launch in mid-August, revenue generation for Brenso Cadab is expected to begin late in the third quarter due to the normal time it takes from commencing selling activities to recording sales. In the case of EraCase, it took nearly four weeks after we launched before the first sales were recognized. As a result of these dynamics, our expectation is that we will only have a few weeks of sales for Brenso Cadab in the third quarter, assuming an approval on the PDUFA date. We continue to see tremendous excitement in the patient and physician communities for the launch, with tens of thousands of patients actively engaging on our Disease State Awareness website, and more than 90% of surveyed physicians in the U.S. indicating that they intend to prescribe Brenzocatib to patients with two or more exacerbations upon approval. On pricing, we continue to expect Brent so cannabis annual us list price to be in the upper half of our original $40,000 to $96,000 range at launch. This update is based on extensive pricing work conducted post Aspen that incorporated Brent so cannabis actual clinical profile to solicit feedback from payers chaos patients and others, giving us a more precise sense for what the appropriate price should be. At the same time, our top priority in launching Brenzocatib is to make access as frictionless as possible, both for physicians and their patients. Our plan will be to deploy a multifaceted market access strategy with the goal of achieving a simple and straightforward prior authorization process to get appropriate patients access to treatment and, equally important, to get those patients seamlessly reauthorized to maintain that access. We believe that this strategy will allow Brenzocatib to reach more patients faster and will result in a smoother runway to achieving peak sales. Now just a brief update on our CRS without nasal polyps study of Brenzocatib. CRS without nasal polyps is a disease with a clear unmet medical need which Brenzocatib could potentially address if it is successful. In the U.S. alone, there are roughly 200,000 patients going in for sinus surgery each year. and several million whose disease is not adequately controlled with steroids. Being able to offer these patients a once-daily oral treatment to potentially help alleviate symptoms and avoid surgery would be a game changer for patients. Our ongoing Phase II BIRTCH trial in patients with CRS without nasal polyps continues to recruit well, and we anticipate top-line results from the study by the end of this year. If successful, the Birch trial would provide proof of concept for the use of a DPP-1 in this disease state and could represent a substantial opportunity that could be similar to or even larger than that of bronchiectasis based on the number of patients who are steroid non-responders progressing towards surgery each year. In addition, a positive result in Birch would serve to further validate the DPP-1 mechanism as a pathway that can potentially offer benefits to patients with a variety of diseases caused by neutrophilic inflammation, including hydradenitis supertiva, for which we have a Phase II study that is currently recruiting patients. Let me now turn to TPIP. The Phase II PAH data readout in the middle of this year is expected to be meaningful in multiple ways. First, it will be the largest study of TPIP to date, with 102 patients randomized two to one, so the results will be the best demonstration of the clinical profile of the drug. And second, this trial is designed with a primary endpoint directly measuring the drug's efficacy in the form of reduction in pulmonary vascular resistance, or PVR. Past studies of other forms of tropostanil have shown PVR reductions in the mid-teens to low 20%. In our view, if treatment with TPIP leads to reductions in PVR that exceed those levels, that result would differentiate it from all other assets in the prostacyclin class, solidifying TPIP's potential value. Before I move on, I want to briefly mention the full Phase II results from the PHILD study, which were presented earlier this month at the Pulmonary Vascular Research Institute's conference in Rio de Janeiro. In addition to the positive topline data that were shared from this study last year, we also showcased a lung imaging study conducted as part of the Phase II trial, which demonstrated a consistent increase of blood volume in the small arteries of the lungs for patients treated with TPIP compared to placebo. While one might expect to see a transient benefit in the small arteries shortly after receiving a dose of proprostenol, the images in our study were primarily captured long after dosing at a median of more than eight hours post-dose and still showed impressive vasodilation of the small vessels. While patient numbers in this lung imaging study were small and should therefore be interpreted with caution, these data provide evidence that once daily dosing of TPIP can achieve important effects on the small pulmonary arteries, even after a significant amount of time has passed after dosing. This supports our conviction that TPIP may provide clinically meaningful benefits to patients with either PHILD or PAH. We remain on track and look forward to kicking off the Phase III trial in PHILD in the second half of this year, followed shortly thereafter by a Phase III PAH trial. Finally, let me touch on EraCase, which continues to drive strong revenue growth across each of our geographic regions. I continue to be impressed with the performance of our commercial teams in the US, Europe, and Japan who are responsible for these extraordinary results. This is particularly remarkable given that the same team was recruiting, hiring, and training 120 new US sales employees last year in anticipation of the BrenzoCat launch. And on top of all of that, they delivered a record-setting year for Aircase sales while also positioning us for success in 2025. This track record of strong execution gives us confidence to provide revenue guidance for our case of 405 to 425 million dollars for 2025 representing yet another year of strong double digit growth for the brand. As a reminder, the strong commercial performance, we have seen and expect to continue to see for our case is all within the currently approved refractory patient population. If the encore trial readout in the first quarter of 2026 positive. it could lead to an expansion of the current label to include all patients with MAC lung disease, addressing a significant unmet need and potentially propelling error case into a blockbuster brand. In short, I couldn't be more excited about our positioning going into 2025. Our commercial engine is humming, our mid to late stage clinical programs are advancing, and our early stage research is accelerating and showing promise. I will now turn it over to Sarah, who will walk us through this quarter's financial results.