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Insmed Incorporated
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Hello, and thank you for standing by. My name is Tiffany, and I will be your conference operator today. At this time, I would like to welcome everyone to the Insmed's Second Quarter 2025 Financial Results Conference Call. [Operator Instructions] I would now like to turn the call over to Bryan Dunn, Head of Investor Relations. Bryan, please go ahead.
Thank you, Tiffany. Good day, everyone, and welcome to today's conference call in which we will discuss Insmed's second quarter 2025 financial results and provide an update on our business. Before we start, please note that today's call will include forward- looking statements 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 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; Roger Adsett, Chief Operating Officer; and Sara Bonstein, Chief Financial Officer.
After their comments, they will be joined by Martina Flammer, Chief Medical Officer, for the Q&A session. I will now turn the call over to Will.
Thank you, Bryan, and welcome, everyone. As I reflect on the first half of 2025, I'm enormously pleased with where Insmed stands as a company and the potential impact we can have on the lives of the patients we serve. Insmed is now three for three, all three of our late-stage assets, ARIKAYCE, brensocatib and TPIP appear to be clear winners with positive Phase II or Phase III clinical data having been produced by each, which is an extraordinary achievement for any company in this industry. These successes have been made possible by the work we put in over the last 18 months across every aspect of our business, including commercial execution, pre-commercial launch readiness, regulatory interactions, clinical development activities, early-stage research and enabling functions.
I could not be prouder of our teams of dedicated colleagues at Insmed. As a result of this impressive operational performance and our solid financial position, flowing both from the performance of ARIKAYCE and our recent capital raise, we feel Insmed is in an incredible position of strength. I want to emphasize that this is just the beginning. The next 12 months for Insmed are shaping up to be extraordinarily impactful.
We expect a steady cadence of meaningful events, both commercially and clinically that have the potential to significantly expand the company's impact on patients and establish Insmed's next wave of products and indications that will drive future growth. If successful, these catalysts could enable us to address more than 2 million patients with serious diseases across multiple products and indications in the coming years. To summarize the progress Insmed has made and highlight what still lies ahead, I'd like to divide our discussion into two sections: our late-stage portfolio and our early-stage portfolio.
Our late-stage portfolio is made up of ARIKAYCE, brensocatib and TPIP. ARIKAYCE continues to perform in its current indication, demonstrating consistent year-over-year growth in its seventh year of launch. We believe we are on track to achieve our full year 2025 sales guidance, driven by continued growth in the U.S., Europe and Japan. Our performance to date has been particularly impressive given that our U.S. sales team has been simultaneously conducting disease state education on bronchiectasis.
In the first half of 2026, we anticipate the clinical readout of the Phase III ENCORE study in patients with newly diagnosed or recurrent MAC lung disease who have not started antibiotics. If ENCORE is successful as ARISE was approximately 225,000 additional patients could gain access to ARIKAYCE driving another leg of growth for the franchise. Moving now to brensocatib, we are days away from potentially launching the first indication for brensocatib in the U.S., representing one of the most anticipated launches in our industry this year. Launches for brensocatib in non-cystic fibrosis bronchiectasis in Europe, the U.K. and Japan are expected in 2026. We also expect top line data from our BiRCh study of brensocatib in patients with CRS without nasal polyps, by the end of 2025 and the interim futility analysis for our CEDAR study of brensocatib in patients with hidradenitis suppurativa in the first quarter of 2026. As we've indicated before, if successful, these studies could unlock a massive opportunity for brensocatib to potentially serve other large patient populations with very few treatment options.
Lastly, TPIP. We have now produced positive results for TPIP in two Phase II studies. We anticipate entering Phase III for PH-ILD in 2025 and for PAH in early 2026. We believe TPIP has the potential to become the prostanoid of choice for the treatment of PAH and PH-ILD pending positive results in these Phase III programs. Turning now to our early-stage portfolio.
This portfolio is made up of our gene therapy operation in San Diego, our de-immunized therapeutic protein operation in New Hampshire, our synthetic rescue research efforts in Cambridge, England, and our research work happening in our original labs based in New Jersey. Across all four of these operations, we have more than 30 preclinical programs in active development. We've historically highlighted that our preclinical research efforts are expected to stay below 20% of our overall spend with the goal of producing 1 to 2 new INDs a year on average. To that end, the last several years have produced significant progress.
Our San Diego research site, which was acquired four years ago, has published encouraging preclinical data in DMD, ALS and Stargardt disease, with the latter representing the first application of our proprietary RNA and joining technology. This research site recently initiated its first Phase I study in patients with DMD with additional INDs expected in the coming years. Our New Hampshire research site, which has been part of Insmed since early 2021 has produced exciting progress as well with its AI-based protein de-immunization platform, demonstrating promising results in preclinical models setting up the possibility for de- immunized proteins to potentially address a variety of conditions, initially looking at uricase and IgG protease.
Our Cambridge England site, which we acquired in 2023, continues to make steady progress on identifying targets for its synthetic rescue platform to potentially be employed against some of the world's most difficult-to-treat diseases such as Ataxia-telangiectasia. More recently, they have also advanced a potential treatment in ALS using a different approach from the SOD1 gene therapy being developed by our San Diego team. Finally, our original New Jersey-based research site continues to be a hub of innovation for Insmed. Not only were ARIKAYCE and TPIP produced from these labs but they have also screened approximately 850 potential next-generation DPP1 inhibitors and are currently conducting pre-IND work for the first of these molecules that we hope will enter the clinic next year.
Consistent with Insmed's core values, a spirit of collaboration and mutual support exists between these sites, they are overseen by a research council, which is comprised of two representatives from each location. The counsel and select members from each of these research sites gather in person twice each year to provide progress updates, offer input and explore ways to collaborate to potentially accelerate the development process. But there's a lot going on in our early research engine, we will only provide regular updates on the programs that have cleared the IND hurdle. In general, we continue to see meaningful progress across each of our early-stage research platforms and are excited for what is to come.
As one example of the progress being made last month, our first patient with DMD was dosed with INS1201, our investigational intrathecally delivered gene therapy as part of our Phase I ASCEND study. Moreover, we anticipate multiple INDs coming from our early-stage research engine over the next year, including our gene therapies for ALS and Stargardt disease as well as our next generation of DPP1 inhibitors. In addition to the advancement of our internal research efforts, targeted business development remains a priority. As always, we will aim to advance the best opportunities that are aligned with our strategy of bringing first and best-in-class therapies to patients facing serious diseases.
With this architecture in mind, it is my hope that you can appreciate Insmed's significant progress while visualizing the exciting future ahead for both our late-stage and early-stage portfolios. Let's now take a few moments to walk through some updates from our late-stage programs, starting with brensocatib. The U.S. launch of brensocatib in bronchiectasis is arguably the most important catalyst for us to get right in the near term. I'm pleased to report that we have submitted our agreement to the FDA about our label.
And from our perspective, we remain on track for a decision on or before the PDUFA target action date next week. Given how close we are to launch, I've asked Roger, our Chief Operating Officer and former Chief Commercial Officer, to share some of his own thoughts on how our launch preparations compare to those he has seen throughout his distinguished career. Let me now turn it over to Roger.
Thank you, Will. Good morning, everyone. It's a pleasure to be with you this morning. As I reflect on the resources invested in the preparation for brensocatib U.S. launch, it's apparent to me that the team is well positioned to execute on this opportunity.
A few things in particular stick out to me. First, I've never seen a company prepare its customer-facing organization so far in advance of the launch. As we've shared previously, we had our sales force fully built out trained and in the field more than 10 months ahead of time. Many companies wait until approval to deploy these resources or elect to do so only a handful of months in advance.
Our proactive decision to expand our commercial organization in this way is one that I believe will result in more patients gaining access to this important therapy and more physicians feeling prepared to prescribe it. Second, I often see companies overlook the importance of developing resources that support the experience of patients and prescribers. If attaining access proves too burdensome for patients or physicians offices to navigate providers may hesitate to prescribe and patients may fail to fill their scripts. It's for this reason that Insmed significantly built out its patient support function called inLighten, which is fully deployed and ready to assist patients and physicians to navigate the complexities of the health care system from day 1. Additionally, while it's common for companies to conduct outreach with payers ahead of new product launches, payer feedback in our early discussions about brensocatib has been particularly supportive of our approach.
The importance of patient access can at times be underestimated in determining a launch of success, particularly when our product is entering a market with no clear competition. I'm pleased that our team has taken nothing for granted on that front. Our prioritization of patient access acknowledges its critical aspect of successful launches and fully aligns with our patient-focused culture. Finally, I want to mention our current understanding of physician enthusiasm headed into this launch.
Based on our interruption interactions with key opinion leaders and our extensive survey work, it is clear to us that physicians have a very high intent to prescribe brensocatib to appropriate patients. And while we know the surveyed physicians often assume they will write more scripts than they actually will in practice, the fact that 90% of surveyed physicians indicate that they indicate to prescribe -- intend to prescribe brensocatib to their patients with two more pulmonary exacerbations over the last 12 months is extremely encouraging. Now as with every launch, not everything will go to plan.
And while there's no way to fully anticipate what challenges may arise, I see our brensocatib team is being prepared to respond to whatever may come. They are equipped with a culture in which raising your hand at the first sign of a problem is championed and they are nimble enough to make necessary adjustments quickly. I also want to remind you that even the best of launches can take weeks from approval to get medicines into the hands of patients. This is primarily due to the time it takes to print final labels and packaging, guide the product through distribution channels and navigate patient access.
As a result, for brensocatib, you should continue to expect only a few weeks of sales for the third quarter, assuming approval by our PDUFA date next week. Having said that, let me emphasize again that everything I've seen from this team's preparation and brensocatib's unique profile leads me to believe that this medicine has the potential to have one of the best launches in the specialty respiratory space. Now let me turn it back to Will.
Thanks for sharing those insights, Roger. I want to stay with brensocatib, but move to its second potential indication, CRS without nasal polyps. As we mentioned on our last call, the Phase II BiRCh study was fully enrolled in April and continues to steadily advance towards its completion. Encouragingly, the Data Safety Monitoring Committee held its second meeting last month to review blinded safety information.
The committee found no safety signals and unanimously recommended that the study continue unmodified. This represents the best possible outcome from this meeting. Recall that the BiRCh trial is testing 10 and 40-milligram doses of brensocatib which is different from the 10- and 25-milligram doses that were studied in our bronchiectasis trials. So it is reassuring that there are no safety signals that have emerged even at a higher dose.
While we continue to expect the data from the BiRCh trial to become available before the end of the year, the exact timing of the top line readout is still being determined, given our usual practice of taking whatever time is necessary to ensure the data are clean to submission level quality. We remain eager to see those data and look forward to what those results could mean for patients. Our Phase II CEDAR study in patients with hidradenitis suppurativa is also progressing nicely with more than 50% of the target enrollment completed. Given the strong enrollment to date, we now expect to be in a position to share the outcome of the interim futility analysis of the first 100 patients in the first quarter of next year.
These two follow-on programs for brensocatib hold the potential to establish DPP1 inhibition as a mechanism that can offer benefits to patients across multiple neutrophil-mediated diseases. Success in either of these indications would add to our confidence both in brensocatib and in the likelihood that our next-generation DPP1 molecules could also serve patients with a variety of other conditions. Turning now to our TPIP program. The clinical highlight of Insmed's second quarter was the top line data release from our Phase IIb trial of TPIP in patients with pulmonary arterial hypertension.
The results exceeded even our most optimistic expectations and established in our view, the potential for TPIP to become the prostanoid of choice in the treatment of PAH. To recap those results, the 35% placebo adjusted reduction in PVR represented the largest treatment effect ever shown in a well-controlled trial, of which we are aware. Additionally, the 35.5 meter placebo-adjusted improvement in 6-minute walk distance produced a p-value well below 0.05, which, despite not being adjusted for multiplicity, was especially striking because the trial was not powered to show a statistical outcome on this measure.
Even more impressive was the fact that these endpoints were measured approximately 24 hours after the latest dose, demonstrating the sustained clinical benefit of the treatment over a 24-hour time frame. With these data, our focus now turns to our Phase III ambitions. We have made significant strides on that front and are on track to kick off the Phase III and PH-ILD in the second half of this year. The work we have done to update the capsule strengths so that doses up to 600 micrograms can be delivered in a single capsule is now complete, and we have engaged with regulators on our plans for trial design, which will allow for dosing up to a maximum of 1,280 micrograms.
We look forward to sharing the details of the PH-ILD Phase III trial design later this year. In addition, our program in PAH is also advancing on schedule. With our final clinical study report of the Phase II trial now complete, we can approach the agency for a meeting to discuss those results and align on a Phase III trial design that will meet the regulators' expectations for approval. We expect that meeting to take place in October, setting up the potential Phase III start in early 2026. Let me conclude my remarks by saying that Insmed is ready.
We have been preparing for years to execute on the enormous clinical and commercial opportunities that lie ahead of us over the next 12 months. If we achieve this, we hope to produce a real and profound difference in the lives of patients living with serious diseases while also potentially creating value for those who have supported us in our evolution to this position. Central to our ability to achieve these ambitions is a culture that supports and empowers our people to do their best work. That is why I'm so proud that Insmed was recently certified as a great place to work for the fifth year in a row.
This is an incredible honor and it is reflective of how our employees feel about working at Insmed. Our people are responsible for all of our successes to date. And similarly, our people will be the ones who will determine our future. This recognition serves as external validation of what I see internally every day that the special culture we have built at Insmed is being preserved even as our team expands.
As a company, we have never been stronger or more motivated to deliver on our mission. I'll now turn the call over to Sara.
Thank you, Will, and good morning, everyone. Let me begin my discussion of second quarter 2025 results by highlighting the strong commercial performance of ARIKAYCE, which is illustrated here on Slide 16. And what may be our final quarter as a single product company, we were pleased to once again deliver double-digit year-over-year revenue growth globally. These impressive results were driven by the highest quarterly revenue figure ever achieved in the United States, along with yet another quarter of extremely impressive performances in both Japan and Europe, all of which was driven by strong volume trends.
In Japan, the 45% growth this quarter resulted from the implementation of new targeting strategies and initiatives to improve the patient experience. For Europe, the 48% growth was driven primarily by strong demand in Germany, Switzerland and Austria. Due to the strength of this performance, we remain on track to achieve our 2025 full year ARIKAYCE net revenue guidance of $405 million to $425 million. As a reminder, this guidance range is specific to ARIKAYCE only and does not include any future revenue contributions from brensocatib, if approved.
On Slide 17, you can see our updated cash balance as of the end of the quarter. This reflects the equity offering that was completed in the second quarter and includes the exercise in full of the underwriters' option to purchase additional shares which in total resulted in the sale of approximately 9 million shares of our common stock at $96 per share, resulting in approximately $823 million in net proceeds to the company at approximately $1.9 billion in cash, cash equivalents and marketable securities as of the end of the quarter, we believe we are extremely well capitalized. Excluding option exercises and proceeds from our recent equity offering, our underlying cash burn for the quarter was consistent with the underlying burn levels that we have seen for the past several quarters, which is remarkable given the additional investments we've made in launch preparations over that period.
Although we don't guide to cash burn levels, in general, we expect our burn will begin to decrease in the coming quarters as the expected revenue growth from brensocatib U.S. launch has the potential to more than offset the expected increases in spending. Moving to Slide 18. You can see our operating expenses for the quarter. Cost of product revenues in the second quarter of 2025 was $28.1 million or 26.1% of revenues which is slightly higher on a percentage basis than our historical performance and reflects the higher proportionate of revenues, which came from outside the U.S. this quarter. Additionally, research and development and SG&A expenses increased this quarter compared to the prior year period.
This increase was primarily driven by investments supporting our commercial readiness initiatives ahead of the expected U.S. launch of brensocatib, enhancements in our international commercial operations and continued funding across our early and late-stage pipelines. In closing, I want to comment briefly on where we are positioned financially as a company and what still lies ahead. We have had a remarkable run of clinical successes over the past 18 months that has transformed Insmed and given us one of the most exciting portfolios of commercial and late-stage assets in all of biotech. Over the next 12 months, we anticipate up to 10 additional commercial, clinical development and regulatory milestones, which we believe have the potential to create incremental value.
With our recent equity financing, we believe we are well positioned to lean in and deliver on each of those catalysts. While we never give guidance on our expected cash runway or timing for achieving profitability for purposes of maintaining financial flexibility, I can say without hesitation that Insmed is in the best financial position in its history. We remain committed to thoughtfully and efficiently deploying our capital to maximize the opportunities ahead of us on behalf of patients. We would now like to open the call to questions.
Operator, may we take the first question, please.
[Operator Instructions] Your first question comes from the line of Jason Zemansky with Bank of America.
Congrats on the progress and really appreciate you taking our question. In conversations with investors of late, there have been some questions over the patient journey given that NCFB and brenso is a new indication. So ahead of next week, I was hoping you could provide some color into what you're doing on a practical level to capture patients. Obviously, interest from the stakeholders are a huge positive, but what are some of the mechanics you're doing to practically move a patient onto treatment?
What are some of the key systems you put in place? And ultimately, what gives you confidence the team can succeed, again, given the challenges that this is essentially a new market that you're building on your own?
Yes, I appreciate the question. I think the first thing to remember is that we've been here before. We did the same exact rollout with ARIKAYCE as the first ever approved product for the treatment of refractory MAC lung disease. And just to remind everybody, because it's a point we like to remember and try to learn from and also celebrate.
When we first came out with ARIKAYCE, I think the average estimate for revenue was $40 million to $60 million in the first year, and we ended up doing, I think, a little over $130 million. So triple what most people thought we were going to be able to accomplish. And I think there's always a reticence that taking on a new indication requires more effort, more work and is more uncertain. But that's why we started as early as we did.
And that's why we got our teams out into the field, as Roger mentioned, starting in October 1 of last year. So the first answer to your question practically is to get people out into the field to do disease state awareness and to build the relationships that enable physicians to reflect on if there is a new medicine that is approved, they know the patient profile that would respond and they can have already thought about that. And so I think we've heard from KOLs and actually community-level physicians that many of them have if you will, a list of patients that they want to turn to that they think are suitable for this right out of the gate.
That information conforms to what we had seen in our research when we went out and sort of sized this market initially, which we've told you is roughly in the U.S. about 500,000 patients that are diagnosed today with bronchiectasis and have an ICD-10 code and all the rest. Of that, roughly half, we think, have had two or more exacerbations in the last 12 months. Down to the physician level, we have now profiled every physician in the United States, and we have information on their expected patient numbers, if you will. So I think we have a very good idea of where all these patients are and how to go about gaining access to them.
We've been putting that in place since we kicked off our disease state awareness campaign literally two years ago at ATS. More practically, as the patients come in, whether the physician calls them over the phone or needs to see them in person either way, once that script recommendation and writing takes place, there's an entire front end of the funnel that will grab the patient and make it available to them to join the inLighten program that Roger made reference to, which is a patient support program, that will help guide them through that process in a compliant and appropriate way. And then there's also all the efforts that the specialty pharmacies will be prepared to make.
We have, at a tactical level across the engagement with patients and physicians and the physicians' offices in a very compliant way, support systems available to ensure that this process is what we refer to as a frictionless launch. And it's our hope that we'll be able to deliver on that. So I hope that gives you a little bit more insight. But I would say, out of the gate, we feel cautiously optimistic that we are ready to engage with this opportunity.
And just one other piece I would just highlight, Jason, is the creation of the COPD Foundation and then creating the 150 care center networks around the United States. And as of last -- the first cohort, I believe, there was about 33 sites identified to be centers of excellence for both NTM and bronchiectasis and sort of the next wave is going to be happening and be put into place very soon. So I think that is also another very tangible piece that's going to help on the patient journey side.
Got it. So is there optimism you can capture these additional asthma COPD patients as well?
So I think at this stage, what we've said is we're initially targeting the patients we know that have been diagnosed as disease state awareness efforts take hold, I think physicians will be asking the question, do I have more patients than I realize? And that's -- we like to say that if you have asthma or COPD and you're in max dose available therapy and you're still experiencing exacerbations that should trigger a question in the physician's mind as to perhaps there's something more going on with the patient. And with the CT scan, they can get the answer to that question. So we're encouraging that reflection so that physicians when they think it's appropriate, will follow that path.
And that would gain access to those patients who are comorbid with COPD or asthma, if those CT scans were to show definitively that they had bronchiectasis and had experienced two or more exacerbations in the last year. If that is the patient profile, then they would be what we would expect to be on label if things go as we expect they will next week. And I think that is a big opportunity, right? We've -- as I said before, 500,000, half of which are two or more exacerbations that are identified right now behind that are multiples of that in size, potential patients, and we'll have to see how that unfolds.
We'll be tracking that one very carefully.
Your next question comes from the line of Ritu Baral with TD Cowen.
Mine is just a follow-up to the previous question. Well, you used an interesting phrase when you talked about payer feedback. You said that the feedback has been positive on the Insmed approach to these patients. And it sounds like it is patients who have a CT diagnosis who have documented 2-plus exacerbations.
Are there other aspects to that Insmed approach or Insmed profile that you can elaborate on, like, for instance, do you have an idea at this point about what sort of prior authorizations outside diagnosis or two exacerbations might be but do you think there might be prescriber restrictions or like other diagnostic requirements outside CT to define that appropriate population? And can you also -- can you also tell us if you plan on providing free drug with launch?
Sure. So I'm actually going to ask Roger to address those questions.
Yes. Thanks Ritu for the question. I think what we anticipate and Will alluded to this as well was just a frictionless launch for brensocatib. And so as we think about that, that is to make the prior authorization process as smooth as possible, as easy as possible for the physicians and the offices that actually usually the ones who process the paperwork and submit that.
And so as we engage with payers, we find some very strong alignment on thinking about the patients who are appropriate for using brensocatib. And so those are the patients with a bronchiectasis diagnosis through a CT scan. Our goal is to have an attestation for the physician that that's the case. That should be -- and I think that, that's a very reasonable position that the payers are also understanding as a reasonable position.
And then the two more exacerbations over the past 12 months because that's the patient population that we studied in the clinical trials. And so we also think that that's an appropriate patient population. So there's a lot of alignment on that. And so I think that part of the alignment is just this is a first-in-disease product and something that there's some excitement about having a solution for these patients that are continuing to exacerbate.
And so it's about aligning on the prior authorization and getting that criteria smooth as possible. And then the second question was around free product, I think it was. And so we aren't planning to do any sampling of brensocatib at this time. But we are making patient support available.
We're helping with co-pays for the commercial patients, et cetera. And -- but no direct sampling to physicians.
Your next question comes from the line of Andrea Newkirk with Goldman Sachs.
I'm looking forward to next week. Maybe I could ask you here with respect to TPIP, as you look to a competitor trial in IPF reading out next month, how are you thinking about the potential for treprostinil to demonstrate an antifibrotic effect there? And what could that then imply for TPIP? And if that study were to be positive, can you just speak to how quickly you could move to advanced TPIP into an IPF study?
Could you move directly to a Phase III or would some other dose finding work need to be completed first?
Sure. I'm going to ask Martina to field that.
Yes. Thanks for the question, Andrea. So with regards to the study, the TETON study that we anticipate reading out, certainly, we will look with great interest to this study, if we see positive results or even trends given TPIP's profile, we would expect that we even have the opportunity to have stronger effects. And so we would be in a position to start off a Phase III study in a very short notice, but we all look forward to these results.
Your next question comes from the line of Jessica Fye with JPMorgan.
So we're just around the corner from brenso's launch. And I wanted to revisit the analog you provided a few quarters ago, we looked at first-in-class, best-in-class respiratory launches. I think at the time, you said those were analogs that any company would strive to even come close to. So I'm just curious, with all the preparation over the past year plus, can you speak to your confidence in brenso achieving a ramp like that?
Sure. So while we're not providing formal guidance as to what we think we'll end up doing -- I do have an ambition that we will fall within reach of those ranges. That's certainly what I would expect to hope to achieve. And the consequence of that would be what I think everyone would observe as a successful launch.
We've done a lot to get ready. But as somebody observed earlier, this is a first in disease launch. And so there's always going to be something that goes bump in the night, and that may influence what we see in terms of performance. It's just impossible at this stage to give any greater clarity or know what the future will hold.
One of the things I did as preparation or grounding exercise is that I spoke to a lot of chief commercial officers at other companies that have been involved in launches recently. And almost to a person, they said that whatever their base case scenario was their ultimate result was wildly off. So it was either much higher or much lower. And I can tell you where I hope we end up.
But certainly, we've done the preparation to accomplish that. But I think the key to that is making sure that we keep in mind the patient experience from day 1. We want the script to be written for the appropriate patient, of course, and support all that, but we really want the patient pull-through because we know that the drug from the Phase III trial and the Phase II trial make patients feel better. And when we saw that data, we were encouraged by that, and we hope that, that will be an experience that they have on the drug and that will reinforce the launch process and I think not in substantial amount of the future performance of the drug will be determined by that experience.
So we look forward to be watching that carefully. It's just one example.
And just one other thing just to remind folks of, as we saw with ARIKAYCE and with all products, it takes a couple of weeks from approval to when you actually start booking revenue. So assuming August 12, PDUFA data took about a month from approval of ARIKAYCE to when we actually started booking revenue. So just reminder to be mindful of that during projections.
Look, our ambition here and our preparation is for this to be a strong launch, and I'll be disappointed if we don't demonstrate that.
Your next question comes from the line of Joe Schwartz with Leerink Partners.
Since your reads on blended blinded data have been pretty accurate heading into past data sets, I wanted to ask if you could expand on the qualitative statements you've made about the BiRCh trial showing positive signs before you unblind it. Is there anything in particular that you're seeing in that data, which makes you optimistic? And then on a related note, can you talk about what factors are included in your statement that you expect to unblind BiRCh this year, but reporting the data is dependent on taking whatever time is necessary to achieve submission level quality. Is there anything in particular which could delay that readout?
Yes. So let me take the second question first. There's nothing that we anticipate with delay. It just people often say, well, the trial, if you're going to have the data by the end of the year, can we then expect it on date X?
And all we're trying to frame out here is that there'll be the generation of the top line results, but that process is longer than simply adding the final days. It can take a couple of weeks depending on what is going on and what frankly is in the database. But we don't know of anything right now that would suggest that there'd be any kind of delay or impediment to that data being available. But we just want to caution people that we are saying it will be there by the end of the year.
We expect that, that will be the case. But depending on how long it takes to sort of clean the database and get a submission ready would dictate when we would ultimately be able to release it. I think your other question was why -- what's the confidence in the blended blinded data. I want to be clear, there's not confidence that we see positive outcomes here.
We don't -- you can't determine that from blended blinded data, and you always have to be cautious in looking at it. What we have seen in the blended blinded data is that the pattern in that blended blinded data would comport with what you would expect to see if the drug were working, that does not indicate that the drug is working. It just means that the profile of patients fits that. So let me give you an example.
If you're going to see a separation in treatment arms, you would expect to see concentrations of patients having certain response measures. While we can't unblind the data to know who's in which arm, we have seen distinctions between groups of patients which would be consistent with different doses providing different results, and it's occurring at a time in the trial when you would expect that to happen. But once again, I want to emphasize, not to overinterpret these results. Our confidence in this being effective in CRS without nasal pulps comes from the fact that really that condition is almost one can think of it like bronchiectasis and the nasal passage.
And so it's not dissimilar from bronchiectasis in that regard. Now that's a pretty rudimentary biological description, but I think it is appropriate to combine those two pieces of information and at least say we are encouraged that this is directionally going the right way. We'll have to see what the results show. And of course, we all know what the experience can be with clinical trial results.
So a word of caution, but I would say we are cautiously optimistic.
Your next question comes from the line of Kelly Shi with Jefferies.
Congrats on the progress. For bronchiectasis launch, do you think the eligible patients have exacerbations properly recorded in medical record for all and any physician feedback on this front. And maybe the strategy implemented in the future help and identify all the eligible patients, if not yet?
Sure. Yes. I mean when we size the market at launch at 250,000 roughly, that is consistent with the data cross examinations and correlations that we've done looking at ICD-10 codes, surveying physicians doing market research. So we feel pretty good about that number as patients that have documented two or more exacerbations within the last 12 months.
The unknown is the opportunity that lies beyond that, and how proximate it is, how many of those patients that are out there that are perhaps comorbid with COPD or asthma and are tracking exacerbations, but have not yet had the CT scan to determine whether or not there is bronchiectasis present. And that's the gold standard that's needed for those patients. So a lot of those patients, I think, are going to get channeled through a CT scan. And I know there are some physicians who are doing that in a very deliberate way, because they do believe that there are patients out there.
Perhaps a way to ground this for everyone is to return to our WILLOW and ASPEN Phase II and III study results, where we had between 15% and 20% of patients in those trials that were comorbid with COPD or asthma, and we saw a response from those patients as well. That's what gives us confidence that if we can access that undiagnosed or misdiagnosed patient population that they'll not only be able to be identified as bronchiectatic but we'll be responsive to the medication, which is, of course, the goal.
Your next question comes from the line of Graig Suvannavejh with Mizuho.
I wanted to ask about your interim futility analysis that you're expecting next year in HS. And if you could remind us what the bar for success will be in that interim. And then maybe a follow-up as you think about next indications for brensocatib, is the view that you will similarly look to do interim futility analyses?
Sure. So I think in response to the second question, we don't anticipate taking brenso into any additional indications beyond bronchiectasis, CRS without nasal polyps and HS. But Martina, maybe you want to comment on the first question relating to the futility analysis?
Yes. So the planning of futility analysis based on the first 100 patients. Just as a reminder, this is an analysis that is -- we're looking for a signal of efficacy, not for a p-value. And that will give us the indication is are we moving forward?
Will we reach a level of efficacy that gives us the confidence that this is a good indication. And -- but you shouldn't be looking for a p-value, but a signal of efficacy.
And the way that's going to work is we're going to -- they're going to actually unblind the data to an expert third-party group of physicians who will look at the data in an unblinded fashion to see if there's something going on there. To your earlier question, really the intersection of the two questions. In HS, it's less obvious and there are fewer gold center animal models that can inform whether or not any particular medicine is going to be effective. So we've gone into patients in Phase II.
But because of that caution and wanting to make sure we're deploying our capital efficiently, we've done this futility analysis, which won't hit the ultimate p-value. It's not going -- we're not going to take an alpha hit on this by doing this because we won't see the results. It's only the expert panel and they're going to essentially give us a thumbs up or down. The trial should continue or the trial should be stopped.
And that's the information we're going to get in the first quarter of next year. While we're not going after other indications with brensocatib, I do want to highlight that we will be entering the clinic next year with our next generation of DPP1 molecules we've been working on since the WILLOW results came out and were so positive. And those will unlock additional indications. We haven't decided what the first one is going to be yet, but we're looking very carefully at things like COPD, like asthma, rheumatoid arthritis and even IBD.
So there's a lot where we can go with this class of molecule. Our confidence will grow with each additional indication that is positive in terms of brenso data. So for example, if CRS and HS were to both work, that would be, I think, a stunning revelation from our point of view, and we would really press the pedal down on the next generation of DPP1 for these other indications because at that point, we believe we would have validated that we're holding something of a biological skeleton key for neutrophil-mediated diseases.
Well, if I could just quickly follow up, just so on your next-generation DPP1, so what then would be an ideal TPP for your next DPP?
Fair enough. We'll have to come up with some new shorthand. I think what we're doing right now, and this is where our confidence comes in that next generation, with the subsequent indications and really the strength of the brenso results in bronchiectasis, we think there is opportunity for this mechanism to apply in other disease states. And that is not entirely neutrophil-mediated disease speculation.
We've done animal models, both with brenso and with the successor molecules. That's why they're basically ready to go into the clinic next year. With that work in hand, we know what each of the different molecules can do in terms of performance in those animal models. And I can tell you that some of those are pretty reliable in terms of their translatability into the clinic.
So I think we're excited by the enormous potential that, that represents because these diseases we're talking about, rheumatoid arthritis, COPD, asthma, IBD, these are very significant indications, and while they may have a number of other approved or competitive products, we still hold by the standard of first or best-in-class. And so if our drug has a meaningful role to play in those settings, you can expect us to be bringing those subsequent molecules forward. And each -- it's our plan right now that each molecule would have its own dedicated disease it would be targeting, which is somewhat unique in an unintended byproduct of the operation of IRA where we are constrained down to nine years to get the return on any investment we make on the molecule.
As a consequence of that, we actually have to go after the other disease indications using new molecules, and that's why we are where we are.
Your next question comes from the line of Andy Chen with Wolfe Research.
Another question about CRS without nasal polpys. Our understanding here is that it's both driven by eosinophils and neutrophils. Just wondering, in your understanding of the disease, is the heterogeneous on a population level as in that there are separate endotypes of different patients driven differently by different cells. Or is it on an individual patient level as each patient is heterogeneous and has contribution from both sides?
It's really interesting. We saw in our ASPEN data that there was not much of a distinction at -- looking at eosinophil levels up to, I think it was 750. And we had originally stratified the study to accommodate for the potential differential performance in the very phenotypes you're describing or endotypes you're describing, where it's a mix of eosinophil and neutrophil-driven disease. That is quite -- we felt a regulatory discovery, and it means that we don't have to worry as much about that, at least up to that threshold of eosinophil counts and those mixed profile patients, we expect to be responsive because they were in the ASPEN study.
As we look forward, that also does open the door to thinking about CRS with nasal polyps, which may be more eosinophil-driven but where we may also be able to have a beneficial effect. So that's something we're reflecting I don't know, Martina, if you want to add anything to that?
Yes. Maybe just with regards to the endotypes, you're right, similar like what you've seen now in bronchiectasis. Endotypes are more defined of what is the biologic driver behind it? So is it neutrophils, is it eosinophils.
And we don't only look at the two big groups. There are subgroup and neutrophils play a role in all of the endotypes. There are -- there is one endotype that is really more driven or largely driven that's eosinophilic, but the largest proportion of patients in CRS is driven by a mixed endotype or strongly neutrophil- driven endotype.
Your next question comes from the line of Vamil Divan with Guggenheim Partners.
This is Daniel on for Vamil. Just another one on the already diagnosed bronchiectasis population. So yes, you described this as being around 500,000 patients, half of which have had 2-plus exacerbations in the last year. So can you maybe discuss if there's any variability between doctors and patients on what they define exactly as an exacerbation in their real-world practice?
I guess kind of getting to the idea that once the drug is available, is it possible that the number of exacerbations that are being identified potentially goes up or maybe they're being under represented right now there's no really drug available for this indication?
Yes. So I think, look, whenever you're talking about a new treatment for a disease that has nothing to treat it, there is a whole cascade of a greater awareness that kicks off. And that almost always results in more patients being identified, more of the symptoms that help identify those patients being tracked and being looked for. You're just raising the index of suspicion among physicians and patients.
And that's really the key objective of any disease state awareness campaign is to ask the question what is causing this set of symptoms that I have. That's also a question that gets engaged with a lot of extra energy now in a world where our drug is approved as we expect next week that opens the door to an answer to the question of what to do if you have it. Whereas right now, a physician who determines that this patient has exacerbations as a byproduct of bronchiectasis, there's nothing they have to offer them other than some basic airway clearance. So I think this is a dynamic that we're very interested to see how it will play out because we are aware of that other significant bolus of patients behind the ones we've identified today that could be eligible for treatment.
And I think the ability for physicians and patients to recognize those exacerbations and document them lays the groundwork for them becoming patients who would be potentially appropriate and, therefore, potentially benefit from the medicine if it's approved as we expect next week. I couldn't be more excited about the possibility to make a dent in this disease space. It's important to remember that this disease has been around since the early 19th century when it was first identified, and it has yet to have anything approved to treat it. So I can't overstate, I think, how significant the arrival of this medicine will be if and when it's approved.
Your next question comes from the line of Jennifer Kim with Cantor Fitzgerald.
Congrats on the progress. Maybe to touch on market access again. I know you said that a simple out-of-station seems reasonable in terms of upfront ease of access. I wanted to ask about the reauthorization process and how those conversations have been going? Or are there any expectations in terms of requirements on that end?
Yes. So our strategy here is the first ever approved medicine and disease, we absolutely do not need to contract if we don't want to in terms of how we're approaching the market access world. We're choosing to do so because our objective with that modest give, if you will, upfront, to create that frictionless launch and reauthorization process. And reauthorization is absolutely a contemplated part of our discussion and negotiation with the market access world.
As Roger said, we've observed that these discussions have been going very well. I think it's fair to say that everybody recognizes the need for a medicine. This medicine's safety and efficacy profile is particularly compelling. So it is not a contentious interaction when we talk about how do we facilitate appropriate patients to get on the drug, how do we ensure that they can remain on the drug and receive benefit.
And I think we're in extremely good state as it relates to that.
And that's helpful. If I could ask one more. Just a question on launch analog, and the dynamics over the next couple of quarters. How should we think about, I guess, the launch in the fourth quarter with out-of-pocket max for Medicare patients and then on that and, I guess, proceeds into 2026 once it resets?
Yes. That's a new feature. Obviously, I'll ask Roger to address that.
Yes. So I think that -- as you think about the smoothing and you think about the Medicare over -- where you can spread out the payments over the full months, I think in the fourth quarter, we probably come in where we're actually in a pretty advantaged position where most patients have probably worked through their copay burden for the full year. We'll see as we go into 2026 and the first quarter, that's a reset that's always historically been a challenge. I'm hopeful that as this will be the second year that this is implemented, that perhaps it's a more smooth process this year as patients and payers and so forth and pharmacies get used to that.
But we'll see. So -- and we stand ready to support as we can our patients in any kind of out-of-pocket burden that we can address directly.
Your next question comes from the line of Leonid Timashev with RBC Capital Markets.
I wanted to ask on the launch, or maybe more specifically how you're thinking about what the shape might be of a launch in Europe and your commitment to Europe and ex U.S. geographies given both the MFN dynamics? And just if there's any differences in how physicians are thinking about their level of excitement for the drug in Europe versus the U.S. as well?
So I would say that the enthusiasm is sort of universal or uniform. Most of the congresses that we go to are international in their scope and engagement. And as a consequence, we have relationships by virtue of ARIKAYCE's approval in the U.S., Europe and Japan with all of those physicians. And so we've had the -- the benefit of their perspective as we've traveled this journey in the development of a bronchiectasis medicine.
And I would say it's equal there as it is here. And so that creates a hopeful opportunity. I think that's echoed by the fact that the regulatory interactions to date in Europe, the U.K. have been extremely positive as they have been with the U.S., and that sets us on a trajectory where we'll be able to launch in Europe and then Japan next year. On the discussion of the issue of how we're going to approach those territories, we have that infrastructure.
We've been very successful with ARIKAYCE in those regions as is so clearly demonstrated this quarter were both outperformed, and I think that's extremely encouraging because that experience and that dynamic that's positive with those physicians in the ARIKAYCE setting we believe will translate over into bronchiectasis. So I think it's a very positive picture. We'll see if the launches will be next year. I'll remind everybody that when we priced ARIKAYCE, we set the list price at the same level in the U.S., Europe and Japan.
We thought that was the right thing to do. That's our best effort to make sure that everybody is investing in the innovation that we're bringing after all these years of development. And so we'll see how this all plays out as we move forward. Hopefully, that addresses your question.
Your next question comes from the line of Trung Huynh with UBS.
This is [ Noah ] on for Trung. Just -- for us, we're wondering, is there any potential read-through from the BiRCh trial to CEDAR if BiRCh readout positive? And then also just looking for a clarification on the futility analysis and CEDAR. We're just wondering, is that focused primarily on the primary endpoint of change in abscesses and modules?
Or do clinical response also play a role in the futility analysis?
I think as you go from BiRCh to CEDAR, I'm just going to say I've said this publicly many times. I'm excited by the possibility of BiRCh because CRS without nasal polyps, again, as I said, rudimentary -- in a rudimentary sense is kind of bronchiectasis and the nasal passage. So I'm hopeful that we'll see some positive results or trends in that study that would encourage us to go into Phase III. HS is a much trickier disease.
And I think there are a number of variables that surround that, which include the patient profile that you're targeting. So we've gone from moderate to severe patients. We could have targeted mild to moderate there's -- in that patient selection process, you introduced some uncertainties about the ability of your drug to have an impact. There aren't great animal models.
So I would put the uncertainty around CEDAR much, much higher than I would have been around CRS at least as far as the logic goes, and that's why we built the futility analysis. So they could go in and look at all the data and make their conclusion about whether this study should proceed because we certainly don't want patients experimenting with the medicine if it's not going to be a benefit. I don't know, Martina, if you had anything you want to add about that?
Yes. And the futility analysis will be focusing on the primary endpoint, so it will be the percentage change of AN nodule count, to week 16. And the reason that is the focus because this is where you see the immediate change as secondary endpoints and by the end of week 52, that we will also look, of course, at high scores, 50 or high score 75. So -- but the interim will focus on the primary endpoint.
Your next question comes from the line of Stephen Willey with Stifel.
Should we expect registration of TPIP development in PAH to be limited to a single Phase III trial? Or do you think a broader sotatercept like development program may be in different functional class and risk subgroups make more sense here just given the strength of the Phase II data?
Yes. I think we'll know more once we've had the October meeting with FDA to be candid. And I think our enthusiasm for this program as we have dug into the data and the aftermath of the top line results, I would say, has grown and accelerated to the point where -- as Martina mentioned a moment ago, the result of the TETON study are going to be something we watch very carefully. We know how sotatercept is perceived and what a positive contribution that is to the disease state.
Remind you that, that can only be operative in PAH. So it doesn't have a role to play in PH-ILD. We're sitting with what we believe to be the best clinical profile based on the Phase II data for PAH, for PH-ILD and now possibly for IPF, depending on how the TETON study reads out. With that set of opportunities, we would then obviously pursue our own data in IPF.
But that's a really significant profile to be in possession of. And so I think we're going to move aggressively after every opportunity. I don't know, Martina, do you want to comment on any of the sub approaches that sotatercept has taken in our approach to that?
Yes. So I think we have to have the discussions with the agency on the number of trials or also how trial designs will look like. We will, of course, take into account that sotatercept is on the market and how we will design the trial, reflecting sotatercept. At this point, we can't speculate of what will be the effect size on top of it, but we know that with the Phase II data, the profile, both on the efficacy and on the safety is the strongest one that we think in the prostanoid group.
So we have very strong confidence level on TPIP, and then we'll see what on top of it, sotatercept, how that would look like. We are also able, and you've seen this in the Phase II study to reach higher doses and therefore, have the opportunity to deliver significant efficacy impact that may sometimes be an opportunity to also go to lower doses on sotatercept, which is a very good drug, but you always look at it in context of what is your overall benefit risk, what is your safety profile. So I think that remains to be seen, but we will design the trial to make sure we can answer these questions.
Your next question comes from the line of Maxwell Skor with Morgan Stanley.
Congrats on dosing the first DMD patient in the ASCEND trial. I was just hoping you could share any early operational and clinical insights into that experience? And how does your intrathecal delivery differentiate 1201 from other gene therapy approaches in DMD?
So I will just say so far, so good. Caution is the watch word around anything to do with gene therapy these days. And we have, I would say, belt and suspenders approach to each and every patient that we are bringing into this. It must be enormously unsettling for parents with kids who suffer from this disease to have experienced what is going on recently in this space.
We set out four years ago when we bought Motus to give support to Bryan's vision that an intrathecal delivery route would improve safety and efficacy. And the early animal data work that was conducted validated those ideas. I think we're anxious to see what the human data obviously will show but we're going to be going very cautiously and slowly given the experience. Recall that part of the reason for intrathecal delivery as an exciting innovation is you don't have that first pass liver effect.
And the consequence of that is you can dose less virus to the patient and notwithstanding all of that, the transduction efficiency that we saw in muscle and even cardiac tissue was remarkable. And so it is for those reasons that we think a lower dose, greater efficacy, potentially greater safety may be the profile of this treatment when it's -- when all is said and done. I want to make one other comment. Actually, Martina, do you want to address that one other issue that we want to make sure people are aware of, that is distinct and important for us versus others in the gene therapy space in DMD?
Yes. One of the advantages right now on the IT delivery that we can -- that we have is we do not have weight-based dosing in our study. And I think that is a different approach also.
We have now reached the end of our question-and-answer session. Ladies and gentlemen, this concludes today's call. Thank you all for joining. You may now disconnect.