Hey, welcome, everyone. Thanks for joining us at the Cantor Global Healthcare Conference. I'm Jennifer Kim, one of the biotech analysts, and I'm excited to be joined by Sara Bonstein, CFO of Insmed, for this fireside chat. Sara, thanks for joining us.
Thanks for having us.
Sara, it has been a transformative year for Insmed, and a special congrats to you for sort of stewarding the company's balance sheet through it all. Maybe to kick things off on a high level, how would you characterize the Insmed story right now, and what brings you the most excitement looking ahead?
Yeah. So thanks, Jennifer, and thanks to the bank for having us here. 2024 has obviously been a tremendous year for Insmed, for our shareholders, for our patients, and all of our partners. It's astonishing to say Insmed is now two for two, and potentially on the track to be three for three. And those are not the normal numbers you think about as you think about this industry. So what do I mean by that? Arikayce, this is our commercial product. We developed it in our own research labs. We remain on track to hit our revenue guidance this year of $340-$360 million.
That represents about a 15% growth year over year as you take the midpoint, and we just had our sixth anniversary of Arikayce, and still able to grow at this rate with a line of sight to a potential billion-dollar product, assuming success, with the label expansion program that's underway right now. Brensocatib, this is a super special one. This is a product we in-licensed back in 2016 . Earlier this year, back in end of May, we were able to put out just breathtaking data with the ASPEN study. So this was a global study in bronchiectasis patients. There is no approved therapy today for these patients, and so amazing on two fronts: one, to potentially have the first approved therapy for this very underserved and needed patient population, and two, to validate a mechanism.
Validating a new mechanism of action as you think about the potential impact that can have on so many lives, it's. You know, you kind of have to, like, pinch yourself that you're part of it. So pretty tremendous. So there's our two for two, right? We validated both of those, and those are moving forward. TPIP, that's our third product. That again is a product we developed in our own research labs. It's backed by treprostinil. It's that's the moiety, right? So as we think about the probability of success there and all those good things, we have a lot of confidence in that program. We'll look to read out our phase II PAH data next year. We read out our ILD data this year.
So, you know, we've answered a lot of science questions of recent, and it's exciting to now have those questions answered and really be moving to the operational front, which we have been able to show year after year, much success there.
Okay, great. Let's jump straight into brenso.
Okay.
So you've talked about over $5 billion in peak sales potential in bronchiectasis alone. Could you lay out the unmet need here and review the data you've shown, and what grounds your confidence behind that projection?
Yeah. So a lot there. Maybe let's just start with what is bronchiectasis? So it's probably the last large respiratory disease that does not have anything approved for patients. It's a chronic, serious lung disease, and what happens to these patients? These patients typically have pulmonary exacerbations. These patients typically get given antibiotics. They get hospitalized each time they have an exacerbation. They have permanent damage to their lungs. Because there's no underlying treatment for it, they treat those acute symptoms, but these continuously happen. There's this cycle of infection and inflammation, lung tissue damage. Patients typically have excess coughing, sputum, infection. We have to do better for these patients. They haven't had anything available for them.
As I mentioned earlier, we just completed our global phase III study that we refer to as ASPEN. It was the largest phase III program ever conducted, about 50% larger than any other phase III program ever conducted in this space, about 1,700 patients. And we put out the data at the end of May. It was as clean as we could have hoped. It was exactly what we would have wanted for these patients. First and foremost, safe and tolerable. So obviously, these are sick patients. We wanna make sure that we can deliver a safe and tolerable treatment to them, so safety and tolerability hit on all of those marks. Primary endpoint, we just talked about exacerbations. That creates lung damage. We wanna reduce the amount of exacerbations. We wanna reduce this lung damage for patients.
So our primary endpoint, reduction in pulmonary exacerbations, and we were able to highly meet statistically significant results in both doses. We had two doses in this program, 10 and 25 mg . So, you know, home run there, and then on the secondary endpoints, we had, you know, a laundry list of secondary endpoints, time to first exacerbation, how long to stay exacerbation-free. Again, we're able to hit stat sig on both the primary and second, on both doses there, and then on our one dose, 25 mg , we were able to show some interesting data on lung function, on quality of life. So really meaningful data for this patient population. Now, let's think about the patient population. Who can we impact here? In the U.S. alone, there's about 500,000 diagnosed patients, today.
This is based on claims data, 500,000 diagnosed patients today. If you think more broadly, where we currently have commercial infrastructure, which is the U.S., Europe, and Japan, it's over 1 million patients, about 1.2 million patients. From a pricing perspective, we've given some ranges for you. We've said we believe the price, based on all the market research we've done thus far, we believe the price will be anywhere from $40,000-$96,000 per year. We obviously have some different flexibility as we think through sort of the strategy on price, and so, you know, you can take those couple of numbers and pretty easily get to, as you put together models, to that $5 billion, and the last piece I would just comment on is, this is only speaking about bronchiectasis.
We are doing additional work in other therapeutic areas, and that is not included in that $5 billion peak sales estimate that we've provided thus far.
Okay, great. And you've guided to NDA submission in the fourth quarter. How is that coming along?
Great! So continue to reiterate that we are on track to file our NDA in the fourth quarter of this year. I would comment that we would look to, you know, share with all of you once that NDA is accepted. That's usually 60 days after filing, and so things, you know, remain on track. Anything we could have done early, we did, and couldn't be more pleased with the team's progress. I would just comment on, we put this data out at the end of May, and to be able to put together this size of data set in an NDA package by fourth quarter of this year is truly remarkable and really speaks to the team and the operational excellence of the folks we have at Insmed.
What are your latest thoughts on filing for the 10 mg versus 25 mg or multiple doses?
Yeah. I mean, dosing will ultimately be obviously FDA's decision. We will put forward our recommendation in our filing. That will ultimately be FDA's decision. What I would just point you to is the highly statistically significant results we saw on both doses. So anything's a win here for patients, and looking forward to hearing back from FDA.
That was gonna be my next question. Would one or the other dose affect the market opportunity, and why or why not?
No. $5 billion net sales peak that we've shared, that's regardless of dose.
Okay, and then the lung function and QOL benefits that you talked about at the 25 mg dose, how are you thinking as far as what might be included in the label, and then also what can be promoted to physicians and patients, and then to payers?
Yeah. The label will be that of the FDA, and we will promote to that. We will obviously promote it specifically to what the label has in it, pending approval, of course. We're obviously very encouraged by the secondary endpoints on lung function and QOL-B on 25, and we'll kind of see where things go from here.
And the pricing range you've talked about, I think Drayton earlier this month said that the work, the research, and payer work that you've done has you sort of squarely in that range.
Mm-hmm.
What information are you sharing with payers to get them there? Are they anchoring those numbers to a particular benefit, and what could sort of move it one way or the other?
Yeah. So, a couple things in that question that maybe I'll touch on. First is we've done multiple pricing strategy work, payer work, pre-data, post-data, and it consistently comes back within that range of $40,000-$96,000, so we feel comfortable in that range. Obviously, we want to focus on access for patient, right? We want to provide the biggest impact we can for patients, and we need patients to have access. So we think anywhere in that range, they will be able to have access. We need to be thoughtful on sort of the pricing strategy as you think about rebating. Do you price higher and rebate more? Do you price lower and rebate less? So we'll think through all of that.
We're in a unique position where we believe, assuming approval, that we will be the first approved therapy on the market for these patients with, you know, little to no competition coming in the near term, and so we have some flexibility as we think about pricing.
So as you're balancing price and access, are there nuances to consider between Medicare versus commercial access?
Yeah. So, I mean, we think that for this patient population will be about 60-65% Medicare. We think that, you know, we'll kind of go through what all the strategies are on the high versus low. We're obviously not gonna share that final decision until we're very, very, very close to launch. But we wanted to share some of this information with you all now, as you're working through your models, and we understand and appreciate what this means to our patients, as well as what it means to shareholders. So hopefully, these additional information help as you go through that modeling.
As we think about payer exposure and the breakdown for brensocatib, does that change from the first year of launch over time, or how do you expect sort of the access to look like at launch versus long term?
Yeah, so I do anticipate there will be a simple pre-auth product, similar to Arikayce. We know that space very, very well. We know how to navigate it. What that means, you know, longer term, I... You know, it's hard to, you know, comment on that today. I would anticipate that they would lean towards the primary and secondary endpoints that they saw in Aspen on the clinical benefit, and simple, you know, attestation to that.
So an attestation, a CT scan? And then-
Attestation on the clinical benefits, as we're thinking about, sort of, reauthorization in sort of the future years.
Oh, I see. Okay, can I ask, so how easy is it to document prior exacerbations? And then, do we have a sense of what portion of the 500,000 patients that you pointed to with, you know, documented bronchiectasis, what % of those patients have documented exacerbation that can sort of hit the ground running at launch?
Yeah, so it's a little hard because it's claims data. So the 500,000 is claims data. What I can say is these are patients that got diagnosed in environments where there was nothing approved. So it leads me to believe that they must have had some symptoms, but again, I can't comment specifically on that due to it being claims data. But a couple other, I think, points that could be interesting here. Specifically, patients that have, as you're thinking on, they need to kind of get through their pulmonologist, right? So a patient usually sees their pulmonologist about two to three times in a year. So that will take time to kind of get them through that funnel.
And we're doing a lot of disease state awareness for the pulmonologist, for the treating physicians, for the patients, for the payers, all that good stuff, so the patients can kind of speak up for themselves. The other thing, and I think where you're kind of probably getting to at this question, is really what does that launch curve look like, and how do we model, right? You guys gave us a peak sales number, and that's super helpful, but how do those early years look? And, we'll be very straightforward. I'm not providing guidance, but I can point to some precedents.
You know, we're a company that very much studies precedent, and as you think about other very successful respiratory drugs in the space, and if you study them and you look at what their first two quarters of launch look like from a revenue perspective, they're in the high double-digit millions of dollars. And you could say that could potentially correlate well with, you know, we've commented for mid-2025 from a launch perspective, pending approval. And then if you look at their next four quarters, which would be, you know, a 12 month period, they're around $500 million-600 million. Dupixent, as an example, that's obviously a product that everyone views as a very, very successful drug. They had, I think, a little over $700 million in their first...
In that like quarter three through six time period. So hopefully that helps, just to give you some frame of reference on very successful launches in the respiratory space, what they looked like. We could not be more thrilled with what this opportunity can mean for patients and getting access to patients is. And having patients have access to this drug is, you know, what we're focusing on, and commercial execution is key to us, and we've been able to show that with Arikayce , and we're excited to be able to show that pending approval next year with brensocatib.
Great. And I think you touched on this, but can you just sort of summarize what you expect plans to require in terms of eligibility and access? I know you said you'd expect a broad label, and then any thoughts on what the criteria would be for long-term use and reauthorization?
Yeah, it's just that pre-auth that we already talked about, which again, we're very familiar with, with Arikayce . And then, what I was kind of commenting on before is, if there's a requirement for the reauthorization after the initial, just that attestation based on, you know, the clinical benefit based on our trial, I would assume.
Okay, great. Can we talk about what you're doing to build commercial readiness ahead of the launch?
Yeah, we've done a lot, so it's interesting. My first day at Insmed was the day we publicly put out the WILLOW data. It was a pretty awesome first day. Hard to beat that, and we have been planning internally for success since then. We had a lot of belief in the WILLOW data, and we were really excited to be able to share the, obviously, the ASPEN data that validated the WILLOW data. So we've been planning internally for quite some time. I can give you some examples. You know, just last year at ATS, so about a year and a half ago, we started external disease state awareness, really helping people understand what is bronchiectasis, how do you diagnose it? What does it mean for patients? All of those, all of those things.
Disease state awareness has been on our radar for quite some time. We've built out our medical team pre-data to ensure that we have the proper education on disease state awareness. We've built out our payer team. We needed the drug to obviously work, but we need to make sure these patients can have access, and they're supported throughout the pricing and reimbursement process. So we brought in a world-class team on the payer side, which has been tremendous. We've done publications, digital campaigns, medical congresses. So you name it, we've you know focused on it. Since the data has been in hand, we have built out our U.S. sales force. So you may recall our U.S. sales force is around 65-ish reps. Pre-data, we've grown that to a 185 reps, round numbers.
So we increased about 120 folks. They are going through training now, and they will be in the field October 1. And as you're thinking about their scale, how much can they, you know, touch? The initial 65 reps, they touched about 5,500 physicians. The increased scale will be able to touch about 20,000 physicians, so a more significant reach. On the payer side, we've had conversations with payers that touch about 90% of patient lives. So a lot of work. We understand and appreciate how important this launch is to all the constituents, from our patients to, you know, all of our shareholders and all of our partners. So we will not leave, you know, one I undotted or one T uncrossed, as we prepare for this launch.
Okay, and those expanded touch points, can you talk about where they're sort of focused on? And I guess thinking about the October 1st coming online, how would that expansion benefit Arikayce ?
Yep. Yep. So, our sales force, we have built now to support Arikayce with its current label, to support brensocatib, assuming approval in bronchiectasis, as well as to support the broader Arikayce label, if that is successful as well. So that it would be the depth and breadth of that 185 therapeutic specialists. We view our therapeutic specialists as community partners embedded in the community. They're not just sales reps, they're community partners for this medical community. On, you know, quote-unquote, "day one," on October 1st, they will obviously have Arikayce as the primary position and be tackling disease state awareness appropriately for bronchiectasis. On the heels of approval, they would then obviously switch to more branding.
Is Arikayce a growing product in 2025?
Yeah. So, as I mentioned earlier, this year, you know, take the midpoint, it's about a 15% year over year, from 2023 to 2024. While I'm not obviously providing 2025 guidance, I believe Arikayce is still a growth brand, which again, is tremendous, given where it is in its life cycle, to still be a growing brand, globally.
... and you've mentioned that Arikayce qualifies for the small manufacturer phase-in next year under the Part D redesign. I guess, what have you said in terms of the expected impact there, and then, of course, on a net basis, the impact?
Yeah, sure. So those meetings already happened. They happened last year. So no sort of new large rebates, and, you know, rebates are one of those it's really hard to take away once you give them kind of a thing. But I think sort of the crux of the question is, what's your gross to net gonna look like as we're trending through this sort of IRA? In 2024, we've obviously provided gross to net guidance, mid to high teens is our gross to net guidance for Arikayce for 2024. Well, I'm obviously not gonna provide gross to net guidance for 2025 at this point.
I think it's fair to say it's not going to decrease, because of this, because you have obviously the trade-offs from the various list price increases and how that flows through inflation, all of those good things. So, I'm very pleased with where we are with gross net, mid to high teens for this year. We've been very, very thoughtful on appropriate contracting to ensure access, but access has been available for patients.
You've also talked about expanding the patient assistance program that's currently in place for Arikayce . Can you talk about those investments, and when is that expected to come online?
Yeah. Yeah. So we pride ourselves on being able to provide, you know, the best patient experience for patients. So we have these coordinators that help with the medical exception process, if the patient chooses to want that support. There's about 10 folks today, helping with that with Arikayce . We'll look to expand that to, you know, forty, fifty, but that'll be closer to launch. That's not something that we need to, you know, put into place right now. Will we bring on a little bit of leadership for it earlier, potentially, but the broader expansion for that would be closer to launch.
Okay. Maybe we can touch on some of the data that's coming up. So you're presenting pre-specified subpopulation data at CHEST next month.
Mm-hmm.
Can you sort of level set expectations for what's going to be shared? And I mean, is the key takeaway going to be consistency, or is there anything-
Yeah.
We should look out for?
So no other shoe to drop. That's the most important thing, right? So we put out our top-line data. It has been very clean. Everything, you know, folks could have expected and wanted to see, so no other shoe to drop on the subset analysis, as you can appreciate. This was a very large study with a lot of patients, and we're, you know, wanting to balance getting this out around the globe at various medical meetings. We were obviously present at World Bronch, which was in Scotland this year, and so we will share additional data, as you mentioned, at CHEST, which is stateside next month. Yeah, just like it's... I can't believe next month is October already, just next month.
So what can you expect to see, the subset data for the primary endpoint and all the subsets that you would expect? Age, race, geography, I know I'm probably missing some, the baseline characteristics, all the standard subset information that you would expect to see, we'll look to share at CHEST.
And then we also, I mean, ERS recently wrapped up.
Mm-hmm.
We saw some data from other DPP-1 inhibitors. I guess the AIRLEAF data for Boehringer and Haisco had phase II data in Chinese patients. Any takeaways on your end?
Mm-hmm. Yeah, a couple things. First is, the disease is the enemy here. Competition is. You expect competition. We plan for competition. It's all embedded in our internal models. It's all included in, the peak sales numbers that we've provided externally. So just wanna ground everyone on, we welcome additional development in these. In across, therapeutic areas, and this is what patients need, is, further, further development. Second is the Aspen data is a pretty high hurdle. The Aspen data was pretty tremendous, and that's going to be a high hurdle for any competitor that wants to enter this space. And, I think that's just a reality. So specifically on the two that you highlighted, AIRLEAF, I think it was honestly best-case scenario, validated the mechanism. They did not show statistical significance.
We'll learn more. They didn't share the placebo rate, which I thought was interesting, but again, disease is the enemy here, but I viewed that best-case scenario with the validation of the mechanism. The data specifically on the Asian China subset that did not surprise us. Like I said, you'll see some subset analysis from us at CHEST, and so, you know, that did not surprise us.
That was an interesting point you made on the subset of Asian patients in your own trial. So is there a reason or a hypothesis on why treatment effect might be particularly strong in that population?
Yeah, I think there's more work we need to do there. It is interesting, but more work to learn.
Okay, fair enough. And then, Arikayce and brenso, they both get a lot of focus, but maybe turning to TPIP-
Mm-hmm.
What is the prioritization for that asset?
Yeah. So TPIP, like I said in the opening, it is, it's a proven mechanism. It's something we developed in our own research lab. We were actually very excited about the ILD data that we put out earlier this year. Appreciate it was weeks before the ASPEN data. It was hard to pay attention to, but a lot of enthusiasm in the medical community on, on our TPIP program and, what that could potentially mean for patients. So it's definitely a priority for the company and excited to put out the, phase II PH data second half of next year.
Are there any key points or considerations as you work on sort of finalizing the phase III plans in PH-ILD?
Yeah. So, as we work through, sort of the next steps for the TPIP program, as I mentioned, the PAH phase II data, second half of next year, as well as the progression of ILD into phase III next year. As we're working through the operational components of that now. It takes time to stand up a global study. So we're working through, you know, CRO selection, site selection, you know, all the things that go along with, putting up a large global phase III program, and we're excited to get that kicked off next year.
Okay. And the other, I guess, upcoming event that might happen is you're wrapping up enrollment of your ENCORE trial for Arikayce . How's that coming along, and can you sort of walk-
Yeah.
- through the next steps?
Yeah. So, we committed to completing screening this quarter, so that remains on track. Once their screens go through about, you know, up to six weeks, then the study is a 13-month duration, so we remain on track for data Q1 of 2026. A couple other updates on that program specifically, we've aligned with the FDA on the endpoint, so that, that was great. Eight questions, quality of life domain, a respiratory domain, so that's, that's tremendous. Or, you know, around 400 patients from a sizing perspective. We're pretty conservative on sizing, but that, you know, gives us more than 90% power, and, again, on track for Q1 of 2026 for that data set.
Just remind us, like, in the off chance that if the trial falls short on QOL-B, what would that mean for your approval in the refractory setting?
Yeah, it's a fair question. I think it's a very, very low risk. Obviously, I can't speak for FDA, but I think it's a very, very low risk. Interestingly, that study is not in our current label, not in the same patient population as our current label. It is on the broader label. So it would obviously be a discussion with FDA, but... and FDA's decision, but that's not something that keeps me up at night.
Okay. Can you walk us through any other big milestones that we should keep an eye on across the rest of the pipeline?
Yeah, I mean, we touched on a lot of them as we went through, but maybe I'll just kinda try and summarize and highlight them for you all here. Obviously, next year is, pending regulatory approval, the potential mega blockbuster launch of brensocatib that you've all been patiently waiting for, and so that is obviously a huge event for the company next year. But there's a lot going on next year beyond that. We'll look to have data in CRS, so that's chronic rhinosinusitis without nasal polyps. That phase II, we'll look to have that data next year, which is also a very significant patient opportunity and value opportunity for the company. We'll look to have the TPIP data, so we'll have the PAH phase II data next year.
We'll initiate the ILD program, continued operational execution and commercial execution on our current label with Arikayce, and the continued progression on the label expansion with the ENCORE program. So a lot going on in 2025. While 2024 was an important year, I think 2025 is gonna be a year for the history books for Insmed as well.
Okay, wonderful. Sara, thank you again for the great discussion, and I'm looking forward to seeing what's ahead.
Yeah, great. Thank you.
Enjoy the rest of your conference.
Thank you.