Chair and CEO of Insmed. Will, thanks so much for joining us. It's been an incredible last 24 hours, but even more broadly, the last year has seen an incredible transformation for Insmed as a story. You know, last night you referenced on Fast Money. This is just the beginning. As you sit here now and you look forward, what can we expect from Insmed?
First of all, I appreciate the opportunity to be here. Yes, I really do believe that this is just the beginning. It's kind of a fascinating time for Insmed because people approach and they say, "Oh my goodness, your data has been good for brensocatib, good data for TPIP." You know, Arikayce is still hitting on all cylinders. You know, how did this come about? I always like to say it's, you know, one step at a time and then all- at- once, 13 years to get to this point. I emphasize all that because this really was a deliberate construction.
We wanted to get to a place where when we flipped the data card on brensocatib for bronchiectasis, we had after that a series of events that would continue almost like a flywheel to drive value as we bring drugs forward that we know are going to make a difference in the lives of patients. If we just take a step back and think about that, our first three late-stage programs have all hits. We are three for three, which is a very rare thing to accomplish, as everyone in this room appreciates in biotech generally, particularly in this kind of a market environment. What does that look like from here? Each one of those has the opportunity to address additional populations.
In the case of Arikayce, we have Encore running that will read out beginning of next year, and that will hopefully afford us the opportunity to go to all MAC NTM patients. In the case of brensocatib, our PDUFA date is August 12. We're on track there. That continues to look good, and that would be the launch in bronchiectasis, followed by data in CRS without nasal polyps. Let me just highlight for everybody, that indication is every bit in our mind as big, if not bigger, than bronchiectasis. That phase two readout in the fourth quarter of this year is going to be a very important event for us. Beyond that, we have a readout in hidradenitis suppurativa of phase two trial using brensocatib to address that condition. The first 100 patients for that will read out in the first part of next year.
Beyond that, we have obviously TPIP, the excellent data that came out yesterday in PAH. We had the good data from last year in PAH-ILD, and that drug now moves expeditiously into phase three trials for both PAH and PAH-ILD. Behind all of that, we also have other compounds that are coming forward into the clinic this year and next, including famously our fourth pillar with several gene therapies, but also successor DPP-1 molecules and other mechanisms of action that are novel that are related to DPP-1 inhibition, which we have unlocked over the course of the last several years as we've done our scientific work around that mechanism of action. Collectively, we think we're bringing forward individual DPP-1 molecules that are successors to brensocatib to address market opportunities like rheumatoid arthritis, COPD, potentially IBD.
Some very big indications will be percolating up in the course of the next several years. We are super excited about all of that. Happily, thanks to the excellent work of our Chief Financial Officer, Sarah Bonstein, we are in a situation where we have roughly $1.2 billion as of the last reported quarter. We are in a very strong position financially to pursue all of these opportunities. It is indeed a very bright day at Insmed right now. As I said yesterday, and I'll continue to say, this is just the beginning.
Great. That's a great overview. Maybe we can dig into TPIP since most recent. Many have probably seen the data, but maybe provide some high-level thoughts here on the data that you were able to see from TPIP and put into context for us how that compares to other prostaglandins, as well as other agents that are currently available in the field.
Sure. The PAH market, as everyone is well aware, is a very competitive market. There are roughly a dozen medicines already approved to treat this condition. It is a fatal condition with a mortality rate of about 50% in five years. From that perspective, there's a clear unmet medical need here. What we were able to bring forward yesterday was, to the best of our knowledge, at least looking at the primary endpoint of pulmonary vascular resistance reduction, placebo-controlled, the best data ever produced in a controlled clinical trial setting addressing that particular primary endpoint for these patients. This is at least arguably one of the better proxies for the pathophysiology of this disease. Reducing pulmonary vascular resistance is a direct measure of how hard the right heart has to work to make up for the constriction of the vasculature, which is the hallmark of this disease.
The challenge of that is historically being able to accomplish vasodilation in a way that is sustained. Most of the drugs in the prostaglandin class that accomplish that do it in a transient way. They have to be dosed multiple times a day or they're given parenterally, which does afford constant exposure, but then it has systemic side effects and also challenges with regard to the amount you're actually able to get to the patient. Collectively, there are gaps in the treatment paradigm. I think what we have done yesterday through our chemistry is really introduce a molecule that accomplishes the original intention behind prostaglandin therapy, vasodilation that is sustained over a 24-hour timeframe with one single dose and accomplishing in two heavily pretreated patients of different functional classes, PVR reduction at 35%, which is really quite a remarkable accomplishment.
I would just add to that two other thoughts. One, the consistency of the data in the secondary endpoint of six-minute walk, 35.5 meters, P- alues that are comfortably very, very low. We were highly statistically significant on the PVR reduction. We also saw NT-proBNP levels drop 60%, which is just remarkable. Some of the other exploratory endpoints we had were also favorable to the TPIP arm. That would be my first point, the consistency. The second is the safety. These were no side effects that were unexpected. We saw a very clean, from our perspective, safety profile. You do see side effects with this drug. That is expected. Indeed, the physician tends to push the patient's dose to the highest tolerable because of the severity of the disease and the interest in seeing the benefit of this drug pulled through.
All that said, the data yesterday could not have been better from our point of view. It really is an exciting day for patients with this condition.
As you think about the profile that has now emerged on the back of this data, where do you see TPIP fitting into the treatment landscape?
Here we would have to take direction from the treating community because what we found when we went out with our target product profile, which was similar to but more modest than what we saw yesterday, was their belief and expression that what we would see is this being used as the cornerstone of therapy in the prostaglandin class, to which other therapies would or could be added, therapies like sotatercept, which are very effective drugs and perhaps as a complement to TPIP, could be very effective in getting these patients almost to a point of normalcy. There is really an opportunity here to think about these patients receiving a clinical benefit that is heretofore unprecedented as a byproduct of the strength and safety of our data and some of the other medicines that are out there.
We absolutely have said from day one, we wanted this not just to be a convenience play. We wanted it to be a clinical efficacy play. We were able to produce that data yesterday. That opens the door to the use of this drug, as expressed to us by the treating community, as the new cornerstone of therapy for PAH patients.
Maybe to underscore that point, you know, prior to the data release, 20% placebo-adjusted PVR reduction had been what physicians had mentioned to you would be clinically meaningful. That extra 15% that you were able to capture here, just speak a little bit more about how much more meaningful that can be.
I mean, I think it is, to use the words of some of the physicians we heard, this data is unheard- of. It was not expected to be this efficacious. It certainly was not expected to see that coupled with a low P value advance on the six-minute walk measure. That's notoriously difficult to capture. I think that extra PVR benefit is nothing short of remarkable. That is what we've heard from the treating community. I think even from the investment community, and as difficult a market as we all inhabit right now, we haven't heard anything but compliments. I think we're about as excited by these data as we could be. The most important thing to realize is that we look at some of these outlier patients who are getting north of 50%-60% PVR reductions within these data sets.
We think that that possibility may be available for patients through combination therapies. That opens a brand new day for patients with this disease. I will also add two important points. Number one, we measured at, I would not call it trough levels, but low levels 24 hours after administration of the drug, roughly. That is a remarkable finding because it means that all of these efficacy data we are talking about are 24 hours after administration. Our assertion that this is a 24-hour coverage is now established by the clinical data. The second is that we went to 640 micrograms as a max available dose to patients in this study. However, in the open label extension, these same treating physicians told us we should consider going to 1280, and indeed we have.
Now there is the possibility that as strong as these data are, there may yet be more efficacy to obtain for patients that are appropriate should physicians want to go even higher. That is going to be a feature and a hallmark of our Phase III design. We will allow patients to go up to a max of 1,280, not 640. That may bring forward even greater efficacy than what we've already seen.
Maybe given the breadth of the data from the Phase III study, the consistency of the signal seen here, is there any potential for this data set to serve as a regulatory submission package?
People always ask, they go right to this, you know, well, you're stat-sig and you hit on all the data points. I love that idea. I think we just have to be very cautious about this and see it very objectively. On the one hand, these data are remarkably consistent. The findings are very compelling. There's no question about that. On the other hand, we only have about 67 patients in this study that received study drug. From a safety point of view, that database is not as extensive as one would normally want to go to the FDA to have that kind of discussion. At the same time, this underlying moiety is treprostinil. There is a world where one could say, well, there's enough understanding of the safety profile of this drug, so they might not feel uncomfortable by that more limited safety database.
I think the short answer is we're going to have the discussion with FDA, hear what their perspective is. For purposes of the investment community, I would just counsel you to assume that we're going to be doing a full phase three program for both PAH and PAH-ILD. These data are very exciting, and I'm caught up in it as much as anybody. I think we have to go and have a sober discussion with the FDA and see where their thoughts are.
Early thoughts on what a phase three could look like here?
We have not put out a lot of detail on that. I think the basic principle would be we want to, as we always do, replicate what we saw in Phase II and Phase III. Not a lot of change, not a lot of novelty. Some people ask about different approaches to Phase III. I think what we have shown here is that on the approvability measure of six-minute walk, we can clearly have an impact even in heavily pretreated patients. Consequently, I think that is the way we want to focus our trial, to be well-powered to accomplish an improvement in six-minute walk because we know that is a reliable, approvable endpoint.
Between the PAH-ILD last year, where we saw a six-minute walk improvement, and again this year in the PAH study, I think we've got enough data to arm ourselves with an estimate of what we would hope to accomplish for approval in a phase three program.
Great. Maybe one last question here on TPIP. Previous estimates were for $2 billion-plus and $2 billion-plus in peak sales for TPIP. How do yesterday's data change that?
I think the market has to evolve along a number of different parameters before we can sort of really give a better view on that. What I would observe is that when sotatercept was acquired for $11.5 billion after it put out phase two data, which I think got to a PVR reduction of about 33.9%, you know, that was acquired at a time when estimates were about $1.5 billion for peak sales of that drug. Today, they sit at around $8 billion. That is a remarkable ambition for that drug and class. I'm not here to suggest that we're going to move to that number, but I do hear that. I think it speaks to the enormous unmet medical need in this space.
I think what Merck has certainly said is that this is a drug that is likely to extend the lives of patients. You can see both an expansion of the pie and a divvying up of it, as it were, based on the strength of the various compounds and data that they can produce. From that perspective, we think this is a very exciting market opportunity. The unmet medical need here is very severe. We are anxious to be able to contribute.
Great. Maybe switching over to brensocatib. Imminent, maybe not imminent, but very soon.
Feels like it. August 12th is right around the corner.
Maybe just to confirm here, how have your, or maybe characterize for us the interactions you've had with the agency recently? Does everything appear to be on track ahead of August 12?
Yeah, bottom line, everything is on track. We're in a good place, on or ahead of schedule with pretty much everything we need to do. The dialogue with the FDA has been consistent and productive. I think, you know, one of the things that we often get asked is, what's your experience with the agency? Our experience is if there's been no disruption at the agency, things have gone very well. We haven't seen big turnover in the team or that sort of thing. From that perspective, I think we're in a very good place. We feel like August 12th is a pretty reliable target deadline. We're ready. I think that's the other important message. Whether it comes on August 12th or earlier or after, whenever it comes, we're going to be ready.
We think it's going to come on August 12, and that's what we're prepared for. We have been practicing on the margin to move earlier should we need to. I would just say that from my perspective, the team has just done exceptional work getting ready. Just to remind everybody, we added all of our therapeutic specialists and had them out in the field as of October 1st of last year. We have been betting on success here. They have been out in the market promoting Arikayce appropriately and also doing disease state awareness about bronchiectasis. We know the physicians, we know where the patients are. We're just waiting for the green light. I've spent time with the leadership team of the therapeutic specialists. I can tell you they're ready to go. Their plans are in place. We have absolutely a world-class team.
I always like to throw out this statistic. We went out to hire 120 therapeutic specialists, and we had over 7,000 resumes. When I say we have the best of the best when it comes to a commercial team, we really were able to pick the folks that we wanted for this opportunity.
With your sales force having been out in the field doing disease state awareness, as you mentioned here, many of these physicians, I'm sure, have been exposed to the ASPEN data, to brensocatib's profile. What is the feedback that your team is hearing as to the interest and the receptivity of physicians to prescribe this?
You know, I would say it's universally positive. The physicians and the patients have been desperate for a therapy to treat these patients for a very long time. I'm brought back to the World Bronchiectasis Conference in Scotland when we put our data out just a little over a year ago. Someone stood up in the room, who was a physician, and said, this is our Vertex moment. We finally have a medicine. I think they were referring to the potential of this medicine to really shape and change the lives of patients with this disease. As a first-ever approved therapy, assuming we get that regulatory approval as we expect, that brings with it a different set of challenges. These are challenges with which we are very familiar because we had the same profile when we launched Arikayce as the first-ever approved therapy for refractory MAC lung disease.
We were conditionally approved for that. We had a great deal of success with that launch. I remind everybody that the street thought we were going to do about $40-$60 million in our first year, and we ended up doing a little over $130 million. The opportunity here is significant. I think we want to be cautious about how fast we run away with potential until we see what we encounter in the marketplace. Clearly, there is an unmet medical need. Physicians are anxious to use this drug. I think patients are as well. We've got now 50,000 plus people that have signed up. I'm getting the sign. How many is it?
53.
53,000, just for the latest number, have signed up on our website as patients wanting information about the availability of this drug. Day one, that's 53,000 people we're going to be targeting to make aware that this medicine is now available. When you think about the background of the addressable market here, we've said it's about roughly 500,000-550,000 patients today diagnosed with bronchiectasis, about half of whom have two or more exacerbations. That means that we've got somewhere between 10%-20% of the addressable market theoretically have already signed up on our website. That's a very encouraging sign.
What are you hearing in terms of the patient profile based off of your market research? The patient profile that would be the first to come on to therapy?
Yeah, I think, look, clearly, patients who are experiencing exacerbations, two or more in the last 12 months, are the target patients we're going to go after. To be specific, we don't think the label will necessarily restrict that, but we think market access will. We're comfortable with that. We think that was the entry criteria for our study. It's appropriate to limit it from the market access point of view to where we know we have the clinical data that demonstrates safety and efficacy. With that in mind, we think it's those two or more exacerbating patients. We've taken note as we've learned more about this patient community that there are a number of patients out there who are seeing their pulmonologist five, six times a year.
These are patients that are clearly symptomatic, struggling with their condition, and the possibility that they're going to be able to have access to a medicine like this, I think we're going to see rapid uptake. Our hope is that we'll be able to facilitate that for physicians who find appropriate patients.
Remind us here the overlap with patients who may have COPD, asthma. What is the overlap of bronchiectasis with these other comorbidities?
It's really the second story behind the addressable market here. And that is that, you know, there are roughly 20 million people in the U.S. with COPD. The literature would suggest somewhere between 4% and 60% of those. It's a wide range, have bronchiectasis as well. So that's a massive potential number. So somewhere in there is a group of patients who have COPD and are very likely bronchiectatic as well. They may be on max dose LABA/LAMAs and still experiencing exacerbations. The success of the Verona launch speaks to those symptomatic patients needing additional support. And importantly, the success of that launch teaches us that these patients are already resident with the pulmonologist. They're not with primary care. And so they are accessible day one.
To be diagnosed with bronchiectasis, you have to have a CT scan, and a pulmonologist has to review your symptoms and designate as such. We are looking for patients who have two or more documented exacerbations in the last 12 months. I think you are going to see patients who are comorbid with COPD and asthma that are going to be coming into the top of the funnel here in a large way. As we think about what that looked like in our clinical trials, we had roughly 15%-20% of patients who were comorbid with COPD and asthma. Importantly, the clinical data showed the drug was just as effective in those folks.
I think there's the identified patients day one, and then there are those who are comorbid who are also going to be folks that we're going to be targeting once they're diagnosed and they have those exacerbations documented.
Maybe speak a little bit about the work you've done on the payer side. You've talked about contracting for access. Maybe talk about the strategy behind that and why you feel that is the right approach.
Certainly with the first-ever approved therapy, we would have the ability to say, this is it, you have to cover it, and have that kind of a posture or dialogue. We think the better way to go is to contract, modest contracting discounts to ensure not just access, which we think we're going to get pretty uniformly, but more the consistency of the prior authorization and to ensure that that process is smooth. Also reauthorization. Those are important elements to ensure that the launch starts with momentum and continues that momentum. That is the strategy behind contracting for access. We think that's going to work very effectively. We're having very specific conversations now, and I would describe those as extremely productive.
As a consequence, we feel like this should be what we term internally a frictionless launch so that a patient gets diagnosed, gets a prescription written by the physician, and then that access back end runs smoothly. That's really what we're after.
The goal of a frictionless launch, what could kind of be a hurdle to that? Is it the diagnosis of patients? Is it the ability of patients to go see their physician to actually come on to treatment? Is it the payer access, the coverage there? What would be the one component you would say is the most difficult?
You know, it's interesting. I just take a step back. I've spent the last several months calling Chief Commercial Officers of other public companies that have had successful launches and asking them what their experience has been with their launch. Almost to a person, they said that the base case scenario they had was wildly off. It was either 3x higher or 3x lower than what they thought it was going to be. That's a byproduct of a number of different factors. In our case, I don't think it's diagnosis or access. I think the biggest challenge will be the back- office fulfillment of the authorization process of a specialty pharmaceutical. That is something that some offices are more comfortable with than others. We're certainly resourced to try to support that in a compliant and appropriate way. That's where we're going to be concentrating.
I will share or confess, depending on your point of view, that the last presentation we gave to our board of directors included a slide that said the three things that went wrong with the launch. It was three blank lines. We do not know what is going to go wrong with the launch, but something will. It always does. Of course, the mindset we need to have is one of responsiveness and flexibility to spring into action to be ready for whatever those challenges may be that present themselves. I think this team is ready. You know, I think about some of the other launches that have occurred recently, and we take note that the preparation for those launches really was constrained to a six-month or even a 12-month preparatory timeframe. We have been ready for launch since ATS, which is in May of every year, two years ago.
We started preparing with disease state awareness, thinking about how to make this launch successful. Through the excellent work of the commercial team and the medical team, we're ready. I think we have the right team. It's absolutely top shelf. Their preparation has been second to none.
Obviously, bronchiectasis, super exciting here, but that's just scratching the surface in terms of other neutrophil-mediated diseases you could go after. You're currently studying them now in CRS without nasal polyps, as well as HS. Speak a little bit more about the opportunity that you see across both those indications and help frame expectations ahead of the data sets that are coming.
Yeah, I want to be really clear about this. What we are trying to do strategically at the company is access novel MOAs that have the ability to create that asymmetric return. They do that by having material impact on disease states where there is a clear unmet medical need. In the case of DPP-1, this begins to look like not just our first molecule addressing a couple of different diseases, but the entire mechanism of DPP-1 inhibition. That is why after we had our phase two data that looked so good in Willow, we kicked off a very aggressive effort to create additional molecules, additional DPP-1 molecules to target other diseases. We think we have unlocked something that is akin to CFTR modulation in terms of its impact on the potential target populationsb
This could continue to yield benefit for different disease states, and that's where we're putting some of our energy. Yes, brensocatib and bronchiectasis had stellar data, but we're looking at CRS without nasal polyps. Just to put that in perspective, there's nothing approved to treat that other than a generic steroid, which we are allowing patients to be on in our Phase II trial. There are currently 32 million people in the United States with CRS without nasal polyps. The incidence rate of surgery and need for treatment for the severe population is 400,000 patients a year right now. That's what we estimate. That is almost as big as the bronchiectasis market diagnosed today, hitting every single year.
If these data are good at the end of the year, and we're hoping that they will be, we have an enormous opportunity, much bigger in my mind than what we're facing with bronchiectasis. We are just beginning. Beyond that, we have hidradenitis suppurativa, which is a phase two study we're running. The background there, neutrophil-mediated for sure, a little bit more opaque in terms of whether or not we're going to be able to have effect. That is a difficult-to-treat disease. We have taken the conservative approach to look at the first 100 patients coming through that trial. We're going to unblind that data to a panel of experts who will then give us a thumbs up or a thumbs down. We will not get any information from it, but we will learn whether or not that trial should continue or if it is futile.
We'll have that information in the first part of next year. Those two disease indications for Brensocatib will create value in just the next 12 months. In parallel, these other molecules I was describing that are coming forward to address COPD, rheumatoid arthritis, potentially inflammatory bowel disease. These are all neutrophil-mediated where we think the DPP-1 may have an efficacy role to play. If that's the case, we're unlocking a real enormous amount of value just around DPP-1. That has a major amount of focus at the company. In parallel, we're also doing Arikayce. We're also doing TPIP, and we're also doing this tremendous pipeline that we haven't spent a lot of time talking about, but which is going to start reading out clinical data next year. We've had a wonderful run here for the last 12 months, but it is truly just beginning.
When we look at something like CRS without nasal polyps, once again, my favorite phrase, blended, blinded data, always be cautious. What we've seen and what we've talked about is that there is enough of a move in the symptom score we're looking at as a primary endpoint to give us conviction that if this drug is working as we expect, we're going to see that very clearly in this data set. More specifically, temporally, that is aligned with the timing of when you would expect the onset of this drug, we are seeing clear symptom relief among patients in the study. Now, we do not know whether they're on drug or not, and that's kind of an important point, but that's a blinded study. When we flip it over the card to find out, we will know.
It certainly gives us a lot of comfort to see that there is symptom improvement. We're hopeful that it is a byproduct of the drug. If that's the case, we're unlocking an enormous opportunity in this fourth quarter of this year.
What is a good result?
What you've seen historically with an inhaled generic steroid is about just under a one-point difference improvement on what's called the total symptom score, which is a score that goes from about zero to nine, and it looks at different measures of symptoms for these patients. We're hoping for basically a one-point improvement. If we can see that, we know that's a path to approval based on precedent. It gives us real encouragement that what we're seeing in the blended, blinded data is actually quite a bit more substantial than that.
That's a one-point improvement over the one point that current standard care has, or that's a...
Yes, it would be. We're looking for a one-point improvement for patients that are heavily pretreated on stable background therapy. These are steroid non-responders. They're patients who've had surgery or multiple surgeries or are eligible for them. These are the severe end of the spectrum, relatively speaking. On the zero to nine scale, they have to come in on that stable background therapy with a score of five or higher. These are highly symptomatic patients. If we can show a one-point improvement for that patient profile, we know we've got a winner.
Great. And then just what does data look like? What does good data look like for HS?
HS, I would just say that what we're looking for there is the first hurdle is a thumbs up that this trial should continue. That will be the beginning part of next year. Once again, we're not going to actually see the data that they're going to look at, but we're going to know whether or not the drug is having an effect. If it is, then clearly a win would be them telling us to continue to run the study.
Great. I'd be remiss if we don't talk about Arikayce at all, your base business here. Maybe just speak a little bit about your confidence on the growth trajectory from here.
Yeah. So again, we're targeting just over $400 million in revenue for this year. I can't remember the specific range. I'm going to get in trouble for it. What is it? $405 million-$425 million. We are still good with that. What I want to just say to people is that's just the beginning because we expect Encore to work. Remember that we did the ARISE study that read out favorably. We think that since Encore was recruited at the same time, it is in effect the exact same study just run for a longer period of time, that it should work. That would give us access to all MAC NTM patients once the regulatory process is completed.
That means by the end of next year, presuming that the data is good in the beginning part of next year, we're going to be in a position where we are filed and waiting for the FDA's response. That would allow us to have another launch right on the heels of the brensocatib launch in bronchiectasis. You're going to see a series of regulatory, clinical, and revenue-generating milestones from this company in the next 12-18 months. They're going to be hard to match in this ecosystem.
Just to remind us, the relative opportunity for frontline versus refractory where you're currently approved.
Between the U.S., Europe, and Japan, it's roughly 30,000 addressable patients that we target, with the majority of those in Japan and the U.S. If you think about all MAC NTM, it increases to several hundred thousand. It is a little over 100,000 in the U.S., a little over 100,000 in Japan, and tens of thousands in Europe. It's an extraordinarily interesting opportunity. Again, nothing else approved to treat this condition. Right now, we're currently the only medicine that is strongly recommended for use in the international guidelines for refractory MAC. We would hope to see that pull through to all MAC NTM.
Look forward to Arikayce Encore data, HS data, CRS data, the launch of brensocatib in bronchiectasis, multiple gene therapies, successor DPP-1s, and another novel mechanism of action that we're working on somewhat secretly within the company that we think is a successor to DPP-1 that would have a role to play in bronchiectasis in the future.
Great. With that, Will, thank you so much. Lots of things to look forward to here.
Thank you very much.