Great. Good afternoon, everyone. My name is Jessica Fye. I'm a Senior Biotech Analyst at JP Morgan, and we are continuing the 42nd Annual Health Care Conference today with Insmed. I'm joined by the company's CEO, Will Lewis, who's gonna give a presentation, and after that, we're gonna move into a Q&A session. If you're in the room, you can raise your hand, and we'll give you a mic, or you can always use the portal to send questions to me on that iPad over there. But without any further ado, let me pass it over to Will.
Thank you, Jess. It is a pleasure to be here today at what is undoubtedly a very exciting moment in Insmed's history. I'm gonna be making some forward-looking statements today. Please review the notice on slide two and our public filings for more information. On slide three, we have framed out that this is the year of Insmed's transformation. I want to open by saying that what I'm about to communicate to you is gonna sound incredibly bullish. Some might even say it's too much, but the truth is that I've been at Insmed for 11 years, and this is the year I've been waiting for. This year, I believe Insmed will undergo a transformation, the likes of which one rarely sees in the biotechnology industry. Those companies that have undergone such a transformation are now well-recognized names in our industry.
We expect to have the answer to whether or not Insmed could potentially experience that type of transformation in the next six months as we release clinical trial results from two of our four core pillars. We are incredibly excited for our phase III ASPEN trial readout of brensocatib for the treatment of bronchiectasis, set for the latter part of the second quarter of this year. ASPEN is not only expected to be the most impactful readout in Insmed's history, but it is also among the most impactful events taking place across our entire sector in 2024. Ahead of ASPEN, we expect to see the first unblinded phase II results from our TPIP program in patients with pulmonary hypertension associated with interstitial lung disease.
Even as we witness those outcomes, we will track the continued progress of our other two core pillars, which hold equally significant implications for the future of our company and the patients we serve. This year, 2024, marks the start of what we believe will be the greatest growth and expansion of our company in its history. We have already grown from 30 to almost 1,000 employees. We have successfully launched our first product in the U.S., Europe, and Japan. We have built our own commercial infrastructure in each of these regions. This past year, we generated over $300 million in revenue from the first-ever approved product to treat refractory MAC-NTM. All of these impressive accomplishments pale in comparison to what I believe is about to unfold.
A year ago, I stood here and said 2023 was the year to build a position in Insmed, given the potential of our upcoming clinical readouts and what they could mean for our future. In fact, Insmed shares gained 55% in 2023, outperforming the biotech index by more than 40 percentage points. This increase in value may be just the very beginning for Insmed, and the team has worked hard to get us into this enviable position. The promise of our future comes from each of our four pillars, shown here on slide four: ARIKAYCE, brensocatib, TPIP, and our early-stage research.
If I can leave you with one message from today's presentation, it is this: We have done extensive commercial work and research, and we believe we can say today that three of our clinical stage pillars have peak market sales potential, each in excess of $1 billion. As I mentioned, our lead product, ARIKAYCE, has just generated over $300 million in revenue in 2023. We believe the ARISE data, released in September, reveals a path to an expansion of the label to treat all MAC-NTM patients. This would mean increasing the number of patients we could treat by multiples of the current market, giving us a path to more than $1 billion in revenue for this product alone. Brensocatib is our second pillar, a small molecule DPP1 inhibitor, which is being developed for both bronchiectasis and CRS without nasal polyps.
The phase III ASPEN study in bronchiectasis is on track to read out in the second quarter of this year, very likely in the latter part of the quarter. If successful, ASPEN would position brensocatib to be potentially the first-ever approved therapy for the treatment of bronchiectasis. As we discuss further, this is a major opportunity and one that has significant overlap with our current commercial footprint and infrastructure. Behind this indication, we've also recently launched a phase II trial using this compound to treat CRS without nasal polyps, called the BiRCh study. Together, if approved, we believe these indications could generate in excess of $5 billion in peak sales. Let me let that number hang in the air for just a moment longer.
If we think about the average multiple applied to establish the intrinsic value of a company, that's usually in the range of 3x-3.5 x. Using just brensocatib, that would imply potentially a value of our company comfortably in excess of $15 billion. Depending upon the strength of data and the success in other indications, there may be additional potential for brensocatib to benefit patients beyond those we have already mentioned. So this could get bigger, but that's not all. TPIP is our third program, and on our third quarter earnings call, we shared blended blinded data that is highly encouraging, suggesting that if it holds up as we progress our clinical research, this could be a best-in-class product and capable of reaching in excess of $2 billion in peak sales.
Finally, under our fourth pillar, we have assembled a diverse group of research teams operating fairly independently, with a recognized leader directing the specific platform technology they are pursuing. Collectively, they are advancing more than 30 preclinical programs, several of which we expect to begin to enter the clinic and produce data in the next one to two years. We believe the assembly of these four pillars, all within one company of Insmed's size, is without peer. As exciting as all of this potential is, the most exciting thing about Insmed is we will have the answers to these questions of whether or not this potential will be realized in the next 6 months, as the clinical trials read out and the data from our programs speaks for itself.
Before we dive more deeply into our future potential, let's turn to slide five, and let me start by reporting that our unaudited global revenues for 2023 were approximately $305.2 million, representing 24% year-over-year growth compared to 2022. I would call out that this comes in above the top end of our raised guidance for 2023 revenues. As we start 2024, we are entering our sixth year since the original launch of ARIKAYCE, and I am pleased to say that despite being that far along in this product's life cycle, we are still forecasting strong double-digit growth in 2024. Our revenue guidance range for full year 2024 is $340 million-$360 million.
This range represents a continuation of the re-acceleration of growth that we have seen for ARIKAYCE since the period in 2020 and 2021 that was most heavily impacted by the COVID-19 pandemic, particularly in the Western world. Expected growth this year is once again anticipated to be driven by the U.S. and Japan. Please bear in mind that these projected revenue levels reflect only ARIKAYCE's current indication of refractory MAC Lung Disease, and it does not consider a potential label expansion in the future. As mentioned before, we continue to progress our development program for ARIKAYCE to potentially expand the label to include all patients with MAC Lung Disease.
On slide six, you can see the relevant patient numbers in each of the major geographies in which we operate for both our current label, which includes refractory patients only, and the number of patients that may be included under an expanded label. Of course, we recognize that for a disease like this, it is unlikely that we would reach 100% of the addressable patients. So while there are roughly seven to 10 times the number of patients that would be included under an expanded label, we anticipate that this would represent a commercial opportunity that is three to five times the size of our current one. Bear in mind that we originally priced this product assuming that this expansion would occur, so we do not expect any significant net price decreases as we add more patients to the label.
Importantly, we believe that this expansion alone, which has already been somewhat de-risked, in my view, due to the strength of the ARISE results last year, would be enough to support our current debt structure over the long term, even without the exciting opportunities represented by brensocatib, TPIP, and our many fourth pillar programs. As we turn to consider the path to achieve the expanded label, I am pleased to report that we have completed our original enrollment target of 250 patients in the ENCORE trial. Consistent with the plans we communicated in September when we released the top line ARISE data, enrollment remains open in 2024. We've submitted our patient-reported outcome data from the ARISE trial to the FDA for their review, and the initial feedback has been positive.
As per our guidance, we will continue to engage with the FDA's PRO experts to gain insights into the appropriate statistical design for the ENCORE study, which is still being finalized. We expect to share the updated enrollment target when that process is complete. I will note that we saw an uptick in the ENCORE enrollment on the back of the ARISE readout, which gives us some confidence in our expected readout timing in 2025, regardless of what the final enrollment target turns out to be. We have not yet had any discussions about a potential accelerated filing pathway with the FDA, and we will not until we have satisfied the requirements of the PRO office. But our base case continues to be that the ENCORE results will be required for regulatory submissions for the label expansion for ARIKAYCE.
All of this is consistent with the communication we released around the ARISE results in September. Turning to slide seven, let's focus our attention on the second of our pillars, brensocatib. It would be an understatement to say that we are excited about the upcoming phase III ASPEN trial of brensocatib in patients with bronchiectasis. As is our practice, we like to define what we would consider success in a trial before we see the data, so there is no ambiguity about what we would consider a win. We must begin, as regulatory authorities do, with an examination of the safety of the trial. To date, the dropout rate in the trial has been consistent or better than what is seen during the WILLOW study.
In addition, after five meetings of the Data Safety Monitoring Committee, no new safety concerns have been identified, and there is again a unanimous recommendation to continue the trial as planned. As we turn to efficacy, recall that the phase III development program for brensocatib in bronchiectasis consists of just one trial, which is why we are looking to achieve a p-value of less than 0.01 on the primary endpoint of the study. It is important to note that although we are studying both a 10 mg and a 25 mg dose in this trial, if either of those doses hits that p-value on the primary endpoint of rate of pulmonary exacerbations, we would consider that a clear win and would pursue regulatory filings as quickly as possible.... ASPEN is well powered to be able to show that result.
In fact, we believe that it would be possible to achieve that outcome with a reduction in pulmonary exacerbations in the low 20% range compared to the control arm. Compare that with the 36% reduction in pulmonary exacerbations that we saw in the phase II WILLOW study, and you can understand our enthusiasm for this trial. Beyond these, which we would consider clear win scenarios, there is an intermediate outcome that would also lead to a filing for brensocatib. Based on discussions with the FDA, if the p-value achieved for either dose falls between 0.01 and 0.05, they would permit us to file ASPEN along with the phase II WILLOW results, which was also a well-designed and controlled study with a statistically significant outcome.
In our view, this is a very credible pathway for potential approval, although it is not as clear a path as either dose coming in below 0.01. As a reminder, brensocatib has been granted breakthrough therapy designation in the U.S. and PRIME designation in Europe, which should expedite our pathway to potential approval. Under an approval scenario, with these regulatory designations, we would anticipate potential commercial launch of brensocatib in the mid-2025 timeframe, with launches in Europe and Japan to follow in the first half of 2026, and preparations for this are already well underway. Any outcome outside of those potentially positive scenarios I just outlined, we would consider a significant disappointment. I remain as excited as I ever, have ever been in the outcome of the ASPEN trial. Everything we have observed so far in this trial is pointing to a potentially positive outcome.
We have an overwhelmingly successful phase II study. We have baseline characteristics in the phase III study that match almost perfectly with the phase II study. We have investigators telling us anecdotally that they are seeing striking results in their patients. And keep in mind that nearly 1,400 of the 1,682 total evaluable patients in ASPEN have completed the entire 12-month study as of the end of 2023. And we have also been cleaning the data as we go, so nearly 2/3 of the total evaluable patients in the study have already had the data cleaned and locked, although it does remain blinded. Slide eight helps to frame out how success in ASPEN unlocks a potential $5 billion+ pipeline in a product franchise by significantly de-risking this new mechanism for addressing neutrophil-mediated inflammatory conditions.
We've already made plans to pursue two additional potential indications, CRS without nasal polyps and Hidradenitis Suppurativa, or HS. If successful, brensocatib would provide a simple once-a-day oral treatment to CRS without nasal polyps patients who have no current approved treatment options, and to HS patients, where current treatment can be onerous and greater efficacy is still needed. The addressable market figures shown here include just patients in the targeted populations who have more severe disease or who are likely to be good candidates for treatment, not the entire patient population with those conditions. At the bottom of slide eight, you can see a timeline of expected updates from this program over the next two years. After ASPEN reads out in the latter part of the second quarter of 2024, we will expect to initiate a phase II trial in HS.
Then, in 2025, after the anticipated midyear launch of brensocatib in bronchiectasis, we would expect to see the top-line results from the BiRCh trial in CRS without nasal polyps. I want to emphasize that as ambitious as this development timeline looks, what is represented on this slide may just be scratching the surface of the potential applications for the DPP1 inhibition pathway. Now let's turn to slide nine to discuss Pillar 3, TPIP. In October, we shared for the first time some of the blended blinded data being generated from our phase II TPIP program. We wanted to share those results because even though they're still blinded, we thought they appeared highly encouraging. You can tell when an expert key opinion leader in pulmonary arterial hypertension says the hemodynamic changes are stunning, that we weren't the only ones who were impressed with the data so far.
The blinded pulmonary vascular resistance reduction data we shared from the PAH trial among responders in the trial, if it's representative of treated patients, would easily best any other treatment of which we are aware. At the request of the investigators in the study, we plan to allow even higher dosing in the open label extension portion of the PAH trial, up to twice the current maximum of 640 mcg to a new maximum ceiling of 1,280 mcg. Since we provided that update, our PH-ILD study was quickly fully enrolled. In fact, it actually over-enrolled with 39 patients rather than the target of 32. We now expect that the top-line readout from that study will occur in the second quarter of this year, ahead of the ASPEN readout.
Enrollment in the ongoing PAH study has also been accelerating, with 45 patients enrolled as of the end of the year. The top-line results from this phase II study are anticipated in 2025. Given the proximity of the top-line results of the phase II PH-ILD study, I want to frame what success for this study would look like from our point of view, and we do this on slide 10. Keep in mind that this is primarily a safety study and is not designed for statistical power to show definitive differences between study arms. What we're hoping to see is a favorable tolerability profile in patients, with the majority being able to titrate up to the highest dose in the trial of 640 mcg by the week five visit....
Any treatment or emergent adverse events, we would hope to be consistent with events commonly observed in patients with PH-ILD. We're also hoping that the pharmacokinetic secondary endpoints being studied, such as NT-proBNP, will be directionally consistent with higher doses and also consistent with the promising preclinical data from this program. However, these PK endpoints, as well as the exploratory efficacy endpoints being studied in this trial, will not be available at the time of the top-line release, but will be shared at a later medical conference. If a favorable safety profile at higher doses and directional alignment between those higher doses and exploratory endpoints is achieved, we would consider it a clear win. Slide 11 gives some context for what the success of TPIP could mean for the many tens of thousands of patients suffering from PAH and PH-ILD around the world.
We are showing here the emerging profile of TPIP on the left of the table, next to the profiles of the other treprostinil products available. Treprostinil is a very effective drug, but it also has properties that limit its usefulness with current therapies. First, it has a very short half-life. Second, the class is associated with adverse events like headache or nausea, which tend to worsen with higher concentrations of the drug in the system. Infused or subcutaneously administered treprostinil try to get around this half-life limitation by allowing for continuous dosing. However, in order to achieve high concentrations in the lung where it is needed, you need to have equally high concentrations throughout the body, which results in adverse effects both at the site of administration and systemically. These can be very difficult for patients.
Oral options have similar issues with GI and systemic side effects because they also use an indirect route to get the drug to the lung. Current forms of inhaled treprostinil products try to solve for those problems by delivering the drug directly to the lungs, which has been shown in animal models to deliver higher vasodilatory effects compared to the same levels in animal models. However, because treprostinil's presence in the lungs is short-lived, before moving into the bloodstream, the current inhaled options must be taken many times a day, causing the amount of drug in the lung to spike and then wane after each dose, which can lead to less than ideal clinical outcomes and adverse events.
TPIP has the potential to offer these patients a solution that combines the best of all of these types of treatments, an even more convenient, once-a-day, inhaled option that could provide continuous effect, day and night, through the slow release of treprostinil directly in the lung as TPIP's 16-carbon chain is cleaved in the lung. Beyond that, TPIP can potentially be safely dosed at much higher levels than other inhaled options, again, because the patient is not inhaling active drug, which could potentially offer better outcomes as well. We are incredibly excited by the emerging profile of this drug and are anxious to see these trials read out in 2024 and 2025. Finally, on slide 12, I want to touch briefly on our fourth pillar, which encompasses all of our expanded research capabilities.
I recognize that our early-stage research is not where some of our investors are focused right now, with all of the near-term catalysts coming from our late-stage portfolio. But this aspect of our company needs to be built now, so it can contribute meaningfully on the heels of the first three pillars. And keep in mind that these efforts are expected to continue to account for less than 20% of our overall spend. We have a lot happening in our early-stage research and development, and we expect to have more updates to share about the progress being made after we have passed some of the late-stage catalysts that are more top of mind. And speaking of catalysts, slides 13 and 14 should give you a sense for the constant stream of catalysts that we expect across our four pillars over the next two years.
As we have discussed today, some of these 2024 catalysts on this slide have the potential to completely transform this company from what it is today, and many are occurring in the next six months. But I would also draw your attention to the many important catalysts that we expect in the second half of 2024 and 2025 as well, which we believe have the potential to build upon our momentum. Moving to slide 15, I am often asked about our financing plans, especially as our stock price has appreciated since the top-line release of the ARISE data in September. Almost always, these conversations surround if and when we might raise more cash through the sale of equity. Although nothing is certain, I will say that we don't currently see any need to do a large equity raise ahead of the ASPEN readout.
Regardless of the ASPEN readout, we believe that there are many potential levers that we could pull that do not involve a large equity raise. These include monetizing TPIP, selling a royalty on one or more of our products, and converting, restructuring, or issuing new debt. I believe we are currently well-capitalized to underwrite the results of literally years of clinical development, even as we continue to deliver and grow commercially. For these reasons, I feel very comfortable with our financial situation. Slide 16 allows me to close by highlighting the greatest strength at Insmed, our culture. Every year, we conduct an internal anonymous survey of our employees to ask them about all aspects of their experience of working within the company.
This year, 91% of our entire workforce worldwide participated in the survey, and more than 90% of those who responded told us that they are inspired and proud to be working at Insmed. They believe in Insmed's future success, and they understand how their role contributes to that future. I see this type of passion and commitment in our people every day, but I never take it for granted, and I know how rare and special it is.... We all share a deep and sincere commitment to help patients by creating and delivering medicines that make a material difference in their lives. As a result, it comes as no surprise to me that for the third year in a row, Insmed was ranked by Science as the number one employer in biopharma.
We were again certified as a great place to work in the U.S., and as but one point for comparison, the survey they conducted indicated that 97% of our employees describe Insmed as a great place to work, compared to the average of just 57% of employees at a typical U.S.-based company. I am enormously proud of the culture we have built at Insmed and what we have accomplished. Our employees are empowered to do their best work for patients, and they bring it every day. Now, with that, I'll be happy to take questions.
Great. Thanks for the presentation, and, as a reminder, if you guys want to ask questions, raise your hand and, someone will bring you a mic. But I'll start. So I want to start not with ASPEN. On ARIKAYCE, you guys just provided guidance. Can you just unpack that a little bit and touch on the commercial dynamics, particularly in the U.S. and Japan, maybe the headwinds and tailwinds you see associated with each region, and what should represent the largest source of growth in 2024?
Sure. So this is working. Is this working? Okay, great. So 2023 was a great year for us. 24% year-over-year growth in the what was the fifth year of the launch of the drug, which is really remarkable, particularly given that it faced the challenge of the COVID era. As we exit 2023 into 2024, our guidance of $340 million-$360 million continues that growth trajectory in the sixth year of launch. We think the majority of the growth will come from the U.S. and from Japan. Last year, we saw Japan accelerate as we expected in the second half of the year, and we expect that momentum to continue.
In terms of headwinds, foreign exchange, there was a price cut last year in Japan that was expected, but the full year effect of that will be this year as well. But I think, and I'm joined here by our Chief Commercial Officer, Drayton Wise, he feels pretty confident that we're going to be able to, to deliver a solid year, again, of double-digit growth.
Maybe sticking with ARIKAYCE, but on the process of just kind of finalizing your discussions with them on the PRO, on the back of ARISE, can you give a little more color on kind of like what the timelines we should expect to hear more about that are?
Sure. So our phase III study that was called ARISE, which read out in September, was an evaluation primarily of a patient-reported outcome tool that we're using to secure expanded access that I talked about during the presentation. So we took the results of that ARISE trial and the PRO work we did, and submitted that to the FDA, and we have heard back from them in a way that we have described as very positive. From here, there will be a face-to-face meeting that will run on their clock, so that will take a couple of months to get accomplished. At that meeting, we expect to finalize all the details about things like minimally important difference, important difference, and other aspects of the PRO.
With that information, we can then finally design the elements of the ENCORE study, which is, what we believe in a base case we will need for full approval and that broader indication. There is a possibility, after we have had that discussion, that we can go to the FDA, and that would be probably, you know, a month or so after the final face-to-face meeting, and ask whether a Subpart H approval, filing here is appropriate. And I think we'll be very anxious to hear the results of that.
Again, I want to be clear, I think our base case is that ENCORE is needed for full approval, but the strength of the ARISE data was so good that we feel it's credible to go to them and ask whether or not they'd be willing to permit a filing with that opportunity in mind, an accelerated approval for the frontline indication. We'll be doing the same thing in Japan. I think the same... I would characterize it the same way. These are credible, but maybe in the category of long shots.
Okay. And can you just remind us of the rationale to keep enrollment open in ENCORE while you're having this discussion with the FDA on the PRO?
Sure. Well, the original design of ENCORE was based off of, you know, no idea what the, what the statistical powering was going to need to be because the PRO had never been tested before. So we took a shot at 250 patients as a guess. We think it'll probably be more than that now, but as it continues to enroll, we are confident that because of the increased enrollment rates we're seeing after the ARISE results, we will successfully complete this trial in 2025.
Okay. Moving to brensocatib. In the presentation, you kind of outlined the kind of like, clear win, file, don't file scenarios. Could you just help me better understand why it's okay if, say, it kind of looked like on the slide that it would be okay if one dose was p-value of less than 0.01, and the other dose kind of like, totally missed?
Mm-hmm.
Is that still a clear win, and can you kind of walk through why?
Absolutely. If you can show in a well-controlled trial at phase III, less than p-value, less than 0.01, that is an approval pathway, clear as day, and so we would file on the basis of that. We brought two doses forward because we wanted to have more than one shot on goal, but neither dose. We don't need both doses to work. We only need one dose to work, and if both work, we might only commercialize one of them.... So this is really about improving our chances of success. I'll remind everyone the raw data here, which is that we were 80% powered to show a 40% reduction in phase II, and we were statistically significant. We are 90%+ powered now to show a 30% reduction on the primary endpoint.
So we are in a good position, and what we like to say is this trial will not fail the drug. We can't control the biology. That's outside of our scope, but if this drug has an effect, this trial is going to capture it.
What's your comfort level on the safety profile here?
I would characterize it, although it's still blinded, as high. The safety profile from phase II, we had a higher dropout rate in placebo than we did in the treated arms. In the current trial, the dropout rate is, as I said, at least as good, if not better, than what we've been seeing. So I think all signs point to positive. We just completed the fifth Data Safety Monitoring Board meeting, and they gave an all-green light to continue, and no safety issues were brought to our attention. It's really important to highlight the safety issue because when you think about how the FDA and other regulators evaluate a drug, they start with safety. And this is a very, appears to be a very safe drug. Consequently, the threshold for efficacy in that risk-reward balance doesn't need to be as high.
So we think that the right level to achieve is at least 15% reduction. We are powered to show down to the low 20s, below 0.01, so this is a very good position for us to be in.
Can I go to some questions from the portal, on brensocatib? Can you give us an update on how the blended event rates are tracking in the ASPEN trial?
So last year, at this time, we put out the blended, blinded data on event rates, and it was 1.12-1.15. We didn't update that this year. We did indicate that if it was going to change materially, we would notify. So you can assume with 1,400 patients having completed 12 months of the study as of the end of the year, that the rates still stay in that kind of a zone.
What do you know about the patients who do have exacerbations when they're on brensocatib? Are those patients just not responsive to drug at all?
I don't know that we have the answer to that question, to be honest. We're still this is a disease where we're trying to reduce pulmonary exacerbations. It'd be a home run someday if a person could find a way to eliminate them entirely. But these patients have this disease called bronchiectasis, which is cyclically degrading. They call it a sort of vicious vortex. And the reason they use that phrase is because you have poor mucociliary clearance that results in the creation of an opportune environment for infection. That infection then leads to exacerbations, and those exacerbations do damage to the lung. It's like a heart attack for the lung, is the way to think about it. And the consequence of that is you then have even worse mucociliary clearance. So the cycle continues.
What we're trying to do with the DPP1 inhibitor is break the inflammatory cascade that is brought on when neutrophils are recruited to the site of the inflammation. By inactivating partially those NSPs or neutrophil serine proteases, we break that cycle of inflammation. Phase II was successful, surprisingly so, across the board. Every patient profile really within the study was positive. We saw these, you know, the assessment of the subgroups, all very responsive, and it was published in the New England Journal of Medicine. It's the first time in almost 20 years, to the best of our knowledge, that they published on bronchiectasis in the New England Journal. So there's a lot of excitement for this drug. We hope phase III mirrors what we see in phase II. The baseline characteristics of the patients are the same.
The design of the trial is almost identical. The only thing we've done is amp up the number of patients that we have in the trial.
How are you feeling about the competitive landscape of other DPP1 programs in development, and can you talk about some of the next-gen DPP1 inhibitors that you're working on?
Yep. So DPP1, our success in phase II resulted in the reinitiation of the DPP1 program at Boehringer Ingelheim. They now have a phase II trial design, suspiciously like our WILLOW phase II study, that will read out close to the same time that our phase III will read out. To the best of my knowledge, they're the only ones that are advancing DPP1. But I suspect that if we have success with ASPEN, you will see a lot of interest in this pathway. And this is an important point. It's not just the treatment of bronchiectasis. That's a major advance, and it's a huge commercial opportunity. But unlocking the value of DPP1 inhibition is like opening the complement pathway.
It's a new mechanism for mediating neutrophil-driven disease, and that opens up a range of other diseases that we could treat, two of which I identified earlier, CRS without nasal polyps and HS. So I think you're not only going to see more interest in DPP1, but its application more broadly. To that end, we have developed similar DPP1s through our medicinal chemistry, which we intend to evaluate for areas that could be of interest, like rheumatoid arthritis, substantial market opportunities that we might pursue ourselves or indeed might partner or sell to other companies. We think this is just the beginning of the DPP1 story.
So maybe switching to TPIP. If you see that, what a clear win scenario for PH-ILD, in a phase II, what are the next steps in that setting?
So we're gonna go right into phase III as quickly as we can on the heels of this study. It is a safety study, but let me just share with the blended blinded data, what really caught our attention and what resulted in the headline that you saw on the slide. These pulmonary vascular resistance reductions are stunning. What we're doing is getting high amounts of treprostinil, which is a drug that's known to be effective, into the lungs of these patients who are very sick. Pulmonary vascular resistance does not tend to spontaneously decrease in patients who have pulmonary arterial hypertension. So if, just to put it in perspective, to the best of our knowledge, so sotatercept had about a 33.9% reduction in pulmonary vascular resistance in their phase II trial.
This is the drug that was acquired for, I think, in the neighborhood of $10 billion, after the phase II results. What we're seeing on a blended, blinded basis across all patients right now, treated and not treated, is a 47% reduction in pulmonary vascular resistance. So we think this drug, it's early. We have to see unblinded data. There are a lot of caveats I need to put out here, but people are really excited about the possibilities here. And the fundamental reason why this is, we believe, working, is we're just getting more of what is a known effective prostacyclin into the patient's lungs. And when you do that, you should see clinical benefit.
Okay. Question, question in the room here? Sure.
In the bronchiectasis, how we say it, bronchiectasis or whatever, the treatment, the protocol, is it a continuous treatment or there are... How the drug would be given chronically or, or, over a...
Acutely, yeah.
Number- Yes, number of cycles or a period of time?
Yeah, this would be a chronic treatment. It's a once-a-day pill. It's about as convenient as you can imagine. I think the person who was representing the American Thoracic Society described it as the holy grail of pulmonary medicine, because it would be a pill taken once a day to treat the last substantial, untreated pulmonary indication. So it'd be taken chronically for life.
Okay.
We have patients, at least one patient I'm aware of, who's been on the drug for more than three years now.
Okay. Thank you.
Maybe just one last one. I know you sort of touched on this in the presentation, but it's a question I get from investors a lot: Is Insmed going to raise money before the brensocatib data?
Well, as you heard me say, I don't see the need for us to do a large equity raise before, but my chief legal officer would remind me that we can't make commitments to anything in particular other than to say that we feel very well capitalized. We had $750 million on the balance sheet as of the end of the third quarter. A little bit more, actually, thanks to the great work of Sara Bonstein, our Chief Financial Officer. And we're in an enviable position to turn over the data cards that are gonna drive what we believe will be very substantial value in this company over the course of the next several months.
Thank you.
Thank you.