Welcome, everyone. I'm pleased to host this Fireside Chat with Insmed Incorporated. I'm Joe Schwartz from the Biotech Equity Research Team at Leerink Partners, and it's my great pleasure to be joined by Sara Bonstein, CFO. Thanks so much for being here to give us an update.
Yeah, thanks so much for having us. We always enjoy the conference, so happy to be here.
Great. Let's start with brensocatib .
What's that?
No surprise there. Where are you at with the regulatory filing, and how has the review been progressing since the submission in December 2024?
Yeah, the interactions with FDA have been really, really encouraging. You obviously saw our announcement on the Day 60 letter, the Day 74 letter for FDA to come back a couple of days early. That's not always what happens. That was really encouraging for us. We continue to have very productive dialogue with FDA. We obviously got priority review. They communicated to us they currently do not plan on holding an advisory committee, our PDUFA, you know, August 12. Really just dotting all the i's, crossing all the t's, having the good interaction with FDA. I couldn't be more pleased with the progress.
Okay, great. Based on our math, it seems like you're within the window of where the mid-cycle review meeting should be happening. How are you feeling heading into that?
Yeah, so not going to comment on some of the, you know, integral steps throughout the process. What I'll say is everything is progressing really well, is encouraging the interaction that we're having, and we're really looking forward to being able to have the first approved therapy for patients with bronchiectasis, obviously pending FDA approval.
Okay, great. Can we talk about the potential label and how you're thinking about the patient population that could be included? Do you think there'll be any language around an exacerbation requirement or anything else that could constrain uptake?
Yeah, so my expectation is the label will be for bronchiectasis. That's obviously what we studied in the trial. The label will obviously be FDA's decision on where we land there. I do anticipate that in the clinical section of the label, they will reference the ASPEN study and the inclusion/exclusion there, which were two or more exacerbations. I think more importantly, it's on the payer side. I do anticipate that the payers will look for two or more exacerbations for their patients. Our goal is to make it as frictionless as possible from a launch perspective for access for patients, for the process for prescribers, and for the payers.
Working through that process now with the payers, those are ongoing conversations, as you would expect, and we'll look through what is appropriate rebating to make sure that we have as frictionless of a launch as possible so we maximize access on day one, as well as the reauthorization, which is obviously very, very critical for this product.
Okay. Does that expectation come from interactions that you've had to date with payers? Can you give us insight into how that's been going, how much work's been done on that front?
Yeah, so we've done a ton of work, as you can imagine. We actually invested with some internal personnel much before the ASPEN data to make sure we had the right skill set in-house. I'm really happy to say that we have the best of the best as you're thinking about the payer group and team and capabilities. That is sort of a check one that we've accomplished. We've done a fair amount of pricing work and studies around what would be acceptable both pre the data and post the data to get very comfortable on what the pricing range should be like, as well as what an appropriate rebating strategy.
We're in a place where we can think about it holistically as we're thinking about price and rebating and access for patients and looking to maximize impact on patient and maximize, obviously, the revenue curve from a value creating perspective. All good. The studies that we continue to do on sort of pricing and access continue to tell us very consistent stories. What we've heard is 90% of physicians do have the intent to prescribe on day one. We continue to get good feedback. We've spoken to over 90% of covered lives on the payer side as well.
Okay, very interesting. How do you expect things to balance out if you're able to get this high degree of market access based on a verbal attestation? What would be required in terms of a gross-to-net or a rebating strategy that would, and how would that translate into a gross-to-net that we can think about when we model the opportunity?
Sure. Yeah, yeah. I love that. We want to make sure we get our models right. That's near and dear to my heart. A couple of things there. Our goal and expectation is that it would be what's called physician attestation. As we're thinking about how do we, again, make this a frictionless launch, make the administrative process as seamless as possible. That would be more of working through what that paperwork would look like. That would be a very simple physician attestation around this is a patient that we believe is an exacerbating patient and have those conversations with payers on what that looks like today, as well as for that reauthorization. Those conversations as we're thinking about gross-to-net and rebating strategy and all that fun stuff. We are not providing formal guidance, so just be obviously upfront with that.
We are obviously ongoing in those conversations. I could not even provide formal guidance, even if I wanted to. What I can say is we have studied a lot of precedents. We have said, let's look across the universe on successful specialty launches. What did gross-to-net look like in those instances, as well as balancing the IRA impact? We all know we need to now understand and comprehend the IRA impact. Insmed will be responsible for the 20% catastrophic coverage for our Medicare patients. Similar mix to ARIKAYCE. We believe there will be about a 60% Medicare population. Off the bat, 60% of 20% is 12%. We believe that will be within our gross-to-net. we will look to obviously launch after the PDUFA date on August 12, 2025.
My expectation is most, if not all, patients will be through their amount, and that catastrophic coverage will be on day one. Twelve percent plus again, studying the precedent, we think anywhere between 25% and 35% seems reasonable at launch based on studying all of that. Again, not formal guidance, but just as folks are thinking about sort of their gross number, their net number. We have provided that pricing range of $40,000-$96,000. From a WAC perspective, we have said we believe it will be on the higher end of that range. The other piece I would just comment on is we have put a peak sales number out there. We said we believe Brenso for bronch alone is a $5 billion peak sales opportunity. That is a net number.
We have taken all of those components into account before we put that number out for you guys.
Okay, very helpful. Thank you. If there is this frictionless launch with only the need for physicians to attest that their patient that they're prescribing Brenso to has had two or more exacerbations in the prior year, how does that work at their level? Are they typically documenting this, or is this documented in healthcare records? Is that even necessary? How many people actually meet that criteria in the United States and are seen by a physician that you can reach with your sales resources?
Yeah, yeah. A lot of good stuff in there. Today, based on claims data, there's about 500,000 patients diagnosed with bronchiectasis in the United States. There's already an approved code, 500,000 in the U.S. Based on what we can see in the claims data, we believe about half of those have two or more exacerbations. You may recall two ATSs ago, quite some time ago, we started investing in disease state awareness. With the hope of approval in August by FDA, this would be a first-in-class, first-in-disease drug. This is the last sort of large respiratory condition that does not have anything approved for patients. We wanted to get ahead of the disease state awareness and get people to be educated on speak up, tell your physician when you have a flare, tell your physician when you have an exacerbation events.
These tend to be elderly female from a patient population. They tend to be the patients that like to take care of everybody else and forget to take care of themselves. It is that stoicism. It is that education of patients having those appropriate dialogue with their physicians. From a reach perspective, we did increase our therapeutic specialists in the U.S. last year. They have been in the field as of October 1. Cream of the crop, as we are thinking about the great folks that are now part of Insmed, so could not be more pleased to have them be part of the team. We added 120 new sales reps. We have about 185-ish reps here in the United States. They will today have ARIKAYCE that are P1 and disease state awareness as P2. That will obviously switch on the other side of approval pending FDA feedback.
That gives us the capability to call on every pulmonologist in the United States. We will still touch on some of the ID docs for ARIKAYCE, but we will now have the ability to call, or we now currently have the ability to call on every pulmonologist in the United States. One other point that I would just like to highlight that I think is important. The COPD Foundation, they recently came out and said that they are working through creating centers of excellence around the United States. We all know that there are those handful of centers of excellence across the United States that really know how to, you know, that excel in the care for both NTM and bronchiectasis patients. The COPD Foundation now has an initiative.
We are the number one sponsor of that initiative, to be full disclosure there, to create 150 centers of excellence around the United States that specialize in NTM and bronchiectasis. We can ensure, so they can ensure that patients receive the best care regardless of what institution they go to.
Very interesting. I think you have some encouraging early indications of market demand by virtue of some of the FDA-compliant outreach that you've been able to do for disease state education and the like. Can you share what you've been able to garner?
Absolutely. Thanks, Joe. How could I forget? We have a disease state awareness website. If you haven't gone out to it, it's really informative. I encourage everyone to look at it. What this disease state awareness site has is we're able to see who's going, you know, how much traffic are we getting on it. Over 900,000 sort of hits on the website. Obviously, you know, Insmed employees go in and look at it a lot, but not 900,000 times.
I've been there a couple of times.
Yeah, yeah. Good, good, good. That's pretty good traffic. I think even more importantly, 41,000 patients have gone in and signed up and want updates. That gives an ability for them to get updates as things progress from an interaction with the regulatory authorities. Patients want something here. These are patients that have gone into their physicians and have been told they have a disease that they can't pronounce and they've never heard of. Then when they ask the physician, what do I do for it, the physician says, there's nothing really we can do for it. Patients are wanting an option here. The ASPEN data that we put out obviously last year was really encouraging. Now it's in the FDA's hands to obviously review all of that and give us feedback.
Interesting. Okay, thank you. Is there any way to envision how many of the 500,000 beyond what you just shared, which is certainly encouraging? Any other way to envision how many of these patients might be early adopters? Are they the patients that have, who are these people that are wanting to stay in touch and might get a prescription before others? Are they any of the certain subsets of bronch? Because we know it's a very heterogeneous population. It's associated with other diseases. Is it those that have more exacerbations, those that have worse exacerbations? What makes any of these patients the right treatment candidate? When will they get a prescription? Do you think it's after an exacerbation or are there other dynamics at play?
Yeah, yeah. A couple of things there. First is what we hear from physicians is they're going to be calling their patients in. I think there's sort of three paths. One, you hear physicians say, we're going to call our patients in. That's obviously really encouraging. The second is these are now patients that are getting educated themselves via the disease state awareness. You see the action in the disease state awareness website and the amount of traffic we're seeing there that they are going to be proactive in their health. Typically, bronchiectasis patients typically see their pulmonologist once or twice a year. Those are sort of the three paths, not just one path. That's obviously very, very encouraging. There is a limit on how many appointments a pulmonologist can obviously have in a day.
There is going to need to be that funnel. Physicians have said that they want to be calling their patients in. I anticipate they would be calling in those patients that are the two or more exacerbations. Those would be the ones that they would be looking to call in initially. I know that there was more to that question and maybe just.
No, I think you covered it. It was a compound question.
Okay, yeah.
Thank you. You have invested a lot in other aspects of the launch too beyond the sales force. Some other field members. Can you tell us who they are and what purpose they'll fulfill?
Yeah. We communicated last year that we obviously expanded our sales force in the U.S. We had about 64 therapeutic specialists in the field to call on ARIKAYCE. We expanded that by the 120 to get to about 185-ish for ARIKAYCE and disease state awareness for bronchiectasis. They'll obviously switch pending approval. We've also brought in some leadership to support the sales organization. Also, just as important on the market access side. With ARIKAYCE, we had field access managers and case managers really to help with that sort of white glove service for patients. We think that is very important for patients to be able to have that additional support. First half of this year, we'll look to expand both our field access managers as well as our case managers. We have expanded our field access managers very recently.
They will be in field shortly. There are about 40-ish of them. Case managers, similar kind of number from an expansion. We did not need to bring them in quite as early as the therapeutic specialists, but obviously want them in field and trained prior to the PDUFA. We think that again helps with that frictionless launch. As you know, we are good stewards of studying precedents. We have studied a lot of really successful launches out there and what works. We have obviously studied our own launch in ARIKAYCE with that being a top 10 rare disease non-oncology launch and learned what worked and what should we kind of expand upon.
Right. That makes sense. Perfect segue to my next question. Then we'll turn to the rest of the pipeline because there's still a lot more to talk about. What launch analogs are you looking at to help frame expectations for the Brenso launch? What is similar for Brenso? What might set this launch apart from others? Are there any distinguishing factors?
Yeah, yeah. Again, we studied precedent of really successful kind of respiratory specialty launches. Things like Fasenra, Dupixent, Ofev, Tezspire, and really studied what their launch curves look like. If you look at the numbers in their first two quarters, and I'll just caveat these are predominantly two full quarters, they were in the high tens of millions from a revenue perspective together for both quarters. If you look at their next four quarters, for all four quarters together, they were around $500 million-$600 million. As you're thinking about what does really good look like, that's what precedent will tell you. Just a couple other, I think, important pieces as you're thinking through that. We obviously have the PDUFA of August 12th.
If you think about just ARIKAYCE as an example, it took about four weeks for revenue recognition from when we got approval. Our reps, we got approval on a Friday. Our reps were in field on Monday detailing, but it did take us about four weeks, which is actually pretty quick. We did everything possible to actually recognize revenue. As you're thinking about that first quote unquote quarter for Brenso with the PDUFA of August 12 and then just the accounting time it takes to recognize revenue, we anticipate that that first quarter will be a week slash a month.
Okay. Great perspective. Thanks.
Yeah.
Okay. Now turning to Brenso's potential in chronic rhinosinusitis without nasal polyps.
Yeah, it's a mouthful. Yeah, yeah.
Yeah. I can't imagine saying it if you had the condition, especially if it was acute.
Yeah.
We've heard that this has a lot of parallels to lower airway bronchiectasis, but yet there's a different endpoint. It's a composite. It's comprised of totally different elements than bronch. Can you help us understand a bit more about this indication and the rationale for studying Brenso here and what you're hoping to see when you report the BIRCH data at the end of the year?
Yeah, yeah. Really excited about the BIRCH data. I'll just remind folks prior to the Aspen readout, we decided that it made sense on a lot of levels to invest quote unquote at risk and move forward into chronic rhinosinusitis without nasal polyps phase two. We initiated that program before the Aspen study and we held off on starting the third indication HS until after the Aspen study. We felt it was the right strategic move to move forward into CRS without nasal polyps before the data because of our strong belief from a mechanistic perspective, as well as we obviously thought it was the right thing to do for patients. Chronic rhinosinusitis without nasal polyps, as Joe was alluding to, has some similarities as you're thinking about sort of the inflammatory nature. It's a neutrophil-driven disease.
The endpoint, while obviously very different from exacerbations, is total sinus symptom score. It has some parallels on sort of like a PRO quality of life. We obviously saw some nice benefit in the 25 milligram arm in the ASPEN study there. The other piece that I will just comment on is, you know, we're starting to, you know, we always, you know, look at what is the data telling us. Everything is obviously all blinded and blended, but we're obviously encouraged by what we're seeing in the two-to-one randomization and some of the separation. We obviously need to wait till the end of the year until we can officially put out the data from a market perspective. We believe that CRS without nasal polyps could be just as big, if not bigger than bronchiectasis. Obviously, more work to do there.
We know we owe that to the market to give some more education on this. The only other piece I would leave you specifically on CRS is we had originally stratified, as you think about eosinophils, and said it needs to be lower than 750, but that the primary endpoint would be on those that were less than 300. Based on now having the ASPEN data and seeing that that is not a driver, we're able to have the primary endpoint be on all 270 patients. That is obviously encouraging as you're thinking about from a market perspective. In the U.S. alone, there are 200,000 patients that get surgery every year. If their options could be get surgery or take a pill that had, you know, if you look at the safety profile in ASPEN and WILLOW, was pretty.
Clean.
Yeah, pretty clean. Yeah. That is obviously encouraging. You have that other layer of the steroid non-responders of another, you know, three million patients. It is a very, very significant market opportunity. As we're thinking about just the layout of the year on the different catalysts, I think that's going to be a really important one for us at the end of this year.
Okay. What kind of a change is clinically meaningful on the endpoint? Is this the same endpoint you'd want to use in phase three? Are you hoping to see stat sig on this endpoint? Any perspective there you can share?
Yeah, yeah. We're 80%. These are patients that on the score of zero to nine, they need to be a five or greater. These are severe patients. We're 80% power to show a 0.97 difference on either of the doses versus placebo or 90% power to show a 1.14% difference on, you know, either of the doses versus placebo. You know, about a one-point change. We believe that will be, you know, meaningful for these patients. If you talk to ENTs and you listen to what they say about these patients, you know, anything that has issue with breathing, that's obviously very impactful for patients. These are patients that have facial pain, that have congestion, that have discharge, and they, you know, need something better than the one available therapy today, which is essentially an inhaled steroid.
Any thoughts on which of the elements of that composite that's captured in the endpoint might have the best chance to move based on the mechanism or the duration of treatment?
Yeah. Because this is a shorter duration of treatments, this wouldn't necessarily be the endpoints of a phase three, but this study, the way it's designed, is going to be able to give us the insight on do we have an impact on these patients over the 16 weeks that they'll have treatments and be able to inform how we should design the phase three, assuming success.
Great. Okay. Of course, I want to make sure we spend some time on TPIP.
Yeah, yeah.
Can you tell us what you're hoping to see in terms of a six-minute walk and PVR benefit when we get the phase 2 b PAH data this year?
Yeah, yeah. We were able to actually move up the timing for our TPIP PAH data to middle of this year. Really excited about that. We had put out some blended blinded data last year really to inform the medical community. We saw the enrollment pick up, which is great. Middle of this year, that will be, you know, here before we know it. As we're thinking about this study, the primary endpoint is PVR, so PVR reduction. If you look at other therapies in this space in the same class, they're sort of in the low to mid-teens to 20-21%, somewhere around there in PVR reduction. We believe if we can get, you know, a little bit higher than that, let's say a 25% PVR reduction, we think that would be a home run.
I'll remind you that our TPIP product, the goal here is to have 24 hours of coverage. This would alleviate the sawtooth pattern impacts that patients are seeing now where they have relief and then it wanes, they have relief and it wanes. This would be consistent relief over a 24-hour period. The other interesting point to call out is we are studying it at trough. We are ensuring that we can show this PVR reduction over that longer period of time, which is a higher hurdle. We did this as a higher hurdle because we want to see will this be impactful for patients. As we think about our mission as a company, it's creating best in class or first-in-class drugs.
While there are a lot of available therapies for PAH patients today, we believe that TPIP, if the product profile continues to hold up, can really be that best in class for a prospect.
Great. Okay. There's been such a focus on the Brensocatib opportunity, but it definitely feels like TPIP can be a needle mover too. Can you give us your view of the market opportunity?
Yeah, yeah. TPIP is probably kind of the sleeper in the company. A lot of focus on Brenso, which I appreciate why. Obviously last year was a transformational event for the company, for our shareholders and for patients. As we're thinking about this year, TPIP, like I said, the data will be here before we know it. We've said $2 billion of peak sales for ILD and PAH, both of those indications. You know, if we can really show an improvement on PVR reduction and provide that 24-hour, this is, I anticipate will continue, is and will continue to be a combination therapy market. These are life-ending type conditions for patients. I anticipate that TPIP is going to be a very significant opportunity for the company.
Okay. Great. Maybe in the time remaining, can we just touch on ARIKAYCE and what the current guidance is for and how you are thinking about, you know, getting to that guidance? You obviously have a ton of insight into this market, which you created and seems to be doing really well still. What should we expect this year for ARIKAYCE? We are very much looking forward to the ENCORE data. How do you feel you're positioned heading into that confirmatory data set?
Yeah, yeah. So ARIKAYCE continues to perform. And, you know, we're in, I think, our eighth year following launch in the U.S. Very significant in 2024. We were able to continue to show double-digit revenue growth. Our guidance for 2025 is $405 million-$425 million on a global basis. That again is double-digit growth. Our commercial team continues to, you know, perform and get out to the prescribing community. It really shows the need for this treatment for patients. I'll remind you the ENCORE program, which that data will be out in first quarter of 2026. That is for a potential label expansion. Today, we're the refractory patient. In the U.S., that's about 12,000-17,000 patients. Total U.S. is about 100,000 patients. It is a significant potential increase. That data, like I said, will be out in Q1 of 2026.
We continue to be encouraged by what we saw in ARISE, which was the first of the two programs. ENCORE looking very similar to ARISE gives us a lot of confidence in ARIKAYCE becoming a billion-dollar-plus product in the near term.
Okay, great. We covered a lot of ground, but we're out of time. We'll leave it there. Thanks so much for the update, Sara.
Thanks so much, Joe. Thanks.