Insmed Incorporated (INSM) Earnings Call Transcript & Summary

Here we go. All right. Welcome, everyone, to the Insmed fireside chat at the TD Cowen Healthcare Conference. I am covering analyst, Ritu Baral. And with me from Insmed is CEO, Will Lewis.

Thank you, Will, for being here. A big couple of years for you guys ever since the BRINSUPRI Phase III data 18 months ago? 2 years ago. We'll start there. That is the major topic of conversation. It is the major topic of conversation yesterday when I hosted you guys for dinner and a number of you guys. You posted very impressive Q4 numbers of 144. I think even buy-side consensus was less than half that. Sell-side consensus was much lower than that even. What are right now, the key drivers behind -- what were the key drivers in Q4? And how is that evolving into Q1? Given the caution that you communicated in January at another investor conference, how is that evolving?

So if I could take one thing out of the last 6 months, it would be the degree of caution we introduced at that other conference because I think that was over-interpreted to mean that in some way, the launch was slowing. I want to be really clear, the launch is not slowing.

So it wasn't a bolus? 4Q was not a bolus?

Well, so bolus is a word that means different things to different people. What I would say is the composition of patients coming into the use of this drug fits a variety of different phenotypes. Let's talk about what those look like. We go all the way back to prior to the -- just after the data. We really kicked off the disease state awareness campaign in earnest. As everyone knows, we brought on our therapeutic specialist force fully 9 months before we even had the drug approved. So with data in hand and awareness increased about the disease state we were out and having very productive discussions with physicians. That put us in a very strong place for the launch, which is what ended up taking place. We'd like to point out that in the fourth quarter of last year, which is our first full quarter, we did more revenue than DUPIXENT did in its fourth quarter after launch. So we have a very strong launch out of the gate here. The patients that came into that, there were 9,000 patients in the fourth quarter that were brought on the drug from more than 4,000 physicians. So we have a very broad group of physicians writing prescriptions, and that's very encouraging. It lays the groundwork for continued success. What's that going to look like? Well, fully half of those physicians have only written one prescription. And so they're testing the drug. They're trying it out in their patient population. The patients will go away, they'll take the drug. And roughly 2 to 3 months after that is when they tend to come back for a checkup, sometimes as long as 6 months, but it's not typically longer than that when you're taking a new medicine. Physicians want to know how things are going. And the stories we're hearing are that the patients on this drug are having a very positive experience in the way they feel, in the degree to which they're still expectorating or coughing. Not every patient is going to have this response, but what we have heard has been extremely positive. So the way we think that's going to play out is each of those physicians who've written only one prescription are going to get that feedback from their patients and their peer physicians, and it's going to make them inclined to write again. So the breadth of prescribing behavior can be something that we can pursue and look to add additional patient volume from as that experience is a positive one. So that's a major driver. Were there any patients that would form some part of a bolus? Almost certainly out of the gate. When a new medicine arrives, there are going to be patients that are, if you will, stockpiled in some of the centers of excellence that are immediately put on drug. There are a lot of physicians, though, as I've just described, there are still trials...

Those were warehouse -- that's warehousing patients. I guess the question is, was there a bolus of appointments in Q4 where the clinicians -- this is how the investors are defining bolus, right? Like the practices cleared room in Q4 for more bronchiectasis patients to come in, have appointments and start drug.

No. There was nothing that was -- that we could discern that would have established that. I do think that there were some warehouse patients...

Which is different.

Which is different. That's why I say the bolus definition is so important.

Okay. So not a bolus as defined by patient starts, more warehousing of patients for sort of the near term '26.

The single most important driver of this medicine in '26 is going to be the experience that patients have on the medicine and the perception that physicians have with regard to it. Now we are a company that has been selling ARIKAYCE for 8 years in the United States. That is a difficult medicine to sell. You have a 30% dropout rate. It's a drug device combination. It takes 15 minutes to administer. And yet despite that, we've had very good success with supporting the sale of that medicine to patients that are appropriate. BRINSUPRI is a once-a-day pill where the placebo rate of adverse events match the treatment rate. So there is a very benign safety profile here. You have a very easy to administer medicine.

So why are you so concerned about this initial treatment experience then? Because you mentioned you want to manage the initial treatment experience, both from a patient and clinician perspective, but it is so tolerable. What's to manage, I guess?

Well, we want to hear that patients are experiencing positive results from the use of the medicine because that increases dramatically the likelihood that they're going to stay on the medicine, that physicians who have noisy patients, by which I mean patients who come in and say, "I'm coughing all the time, I'm expecting all the time. I can't go out in public. I have these flares that keep me home from work, et cetera." If those patients, and we've heard these stories, come in and say, "I'm no longer coughing. I'm no longer expectorating. My energy is back." Now not every patient is going to have that same experience, but we have seen a lot of public social media discussion by patients a very positive circumstances most dramatically. I read at a different conference, one of the comments from one of the patients who had gone into their physician's office, and it was the physician who relayed this to us, and have broken down in tears because they had described their life as being back in their control, that this was a miracle drug, et cetera. Now I want to be cautious for everyone who's listening, we are not advocating for this to be the experience that everyone is going to have on the medicine, but we have heard these anecdotes, and we consider those to be encouraging and powerful forces among the network of physicians that will make them inclined to write again and again and again.

So in the unknown unknowns that we talked, that you mentioned in January, one of the -- a few of the points were co-pay smoothing, payer contracts, inventory dynamics. Last contracting or at least major plans put in place, how have those evolved and your confidence through full year '26?

So the way I would simply describe this as looking at our dashboard, everything is green. We couldn't be happier about the persistence rate, the uptake, the approval, everything is going the way we want it to go. Where that's going to lead us is the great unknown that I think is probably the subject of attention from everyone on the street because we said initially the 250,000 patients who are diagnosed today with 2 or more exacerbations that we know are out there because they are on the roles as having been diagnosed with this condition with 2 or more exacerbations, that 250,000 patients, that gets us to peak sales in excess of $5 billion. Now as we think about other populations and the top of the funnel getting filled, we start to think about the other 250,000 diagnosed patients who have between 0 and 1 exacerbations a year. Now those patients right now are on label. We're not targeting them as intensely because we're trying to work with the insurance companies and the physicians who say that the bulk of the patients they think are appropriate for the medicine at this time are those who are in the moderate to severe category, those with 2 or more exacerbations. So by working with the insurance companies and agreeing to that restriction to only going after those patients that were studied in the ASPEN trial, we are never going to be friends with the insurance industry, I don't think. But we certainly are trying to meet them halfway. And I think that is why as market access dynamics continue to look good, we don't anticipate a slowdown from the implementation of new insurance policies. That's the single most important distinction about market access. You start out, everything is a medical exception. We have the infrastructure and the experience to do that because we've been doing it for 8 years for ARIKAYCE. As the policies get established, they can be more or less restrictive than what you have been bringing online. In our case, it parallels what we've been doing to date. So that this targeting of 2 or more exacerbations in the last 12-month patient profile is, in fact, the sweet spot we're going after. It's where the insurance companies are setting their policies, and it puts us in a very good place to continue to see the kind of uptake as we like to say, up and to the right since the launch of this drug.

So with that access getting expanded in Q1, are you -- and this green across the board that you mentioned, are we taking the possibility for flat to down Q1 off the table?

So I'm not permitted to give any prediction about the quarter. Well, that's the entire front row from Insmed is now saying, "Don't answer that question, Will." The -- I will just say that I think we feel good about where we are. And the way we tried to address this because I know there was concern, we did express some caution at the beginning of January. But I want to reemphasize that caution we expressed was not because we were in possession of some information that gave us pause. It's because we knew some people were going to run away with the prediction of what this revenue could become. We had originally stated analogs for great performance in quarters Q2 through Q5 would be somewhere in the $500 million to $700 million range. Everybody thought that was outrageously high that we would never hit it. And now most of the estimates that are out there are north of $1 billion for that same time frame. So everybody has run away and believe that this has now greater potential. And that's a very exciting place to be. I just want to remind everybody, to the best of our knowledge, there are 15 products in the history of our industry that have ever cleared $1 billion in quarters 2 through 5. J&J has never done it, Merck has never done it. The drugs that have done it are things like COVID vaccines, GLP-1s, Harvoni, Skyrizi; there are not that many that have gotten there. And every company that has ever accomplished that, not one of them has been worth less than $70 billion. So from our perspective, we think we've got the right product. We think it's going to do very well, and we think that's extremely well for the company's future.

So you mentioned that $1 billion of new guidance at floor. And as I mentioned last night, consensus is already at 1.2 right now...

And you're wondering why we introduced caution at the beginning of January. I wonder.

You made me talk my original $800 million down, and then I had to take it back up. So that's an extra note. But if we look at how you're going to meet or exceed the 1.2, certainly beat the 1, what are those levers? Is it expanding lives covered? Is it more guidance? I mean you already haves in [ upper ] included in some guidance, rest of world, depth of prescribing, breadth of prescribing?

Yes. So it's a great question. I think the single most important thing that will drive it, as I mentioned before, the storytelling, the peer-to-peer dialogue among physicians, what is the experience with this medicine? How are your patients doing on the medicine? And what we hear repeatedly is positive feedback there. So that's good. That should enable us to take advantage of the more than 4,000 physicians who've written at least 1 script to encourage them to write a second or a third. And you can imagine if that is accomplished just with the physicians we've already reached and convinced that the medicine should be written that those are easier to activate to write 2, 3 or 4 prescriptions. And that's going to be the first area of focus. So that becomes depth from the breadth that has already been established, right? We want to see the breadth continue to grow, right? 4,000 physicians is still just scratching the surface of the 27,000 pulmonologists in the United States. But with those 4,000 physicians writing and getting as many patients as we have on drug already, it's 11,000 change as of the end of the fourth quarter. We're targeting 250,000 patients who are diagnosed with documented 2 or more exacerbations.

In the U.S.?

In the U.S. alone. So we are just scratching the surface out of the gate. And it's very dramatic, I understand, to come out and say we'll do north of $1 billion in revenue with only 1 full quarter under our belt. But that gives you some idea of where our confidence level is as we look out at this year and beyond.

And so ex U.S. is not part of this $1 billion. It's not -- I mean, when does ex U.S. start factoring in and current thoughts on how to balance the existential MFN threat?

Yes. So right now, we are approved in Europe, and we're approved in the U.K. We have not launched in either of those locations because we're waiting for clarity around MFN. It was not going to be a material part of our revenue this year. Europe continues to perform very well with ARIKAYCE. Japan, even more so, both in terms of what ARIKAYCE has done over there. They were a huge contributor to last year, and they're hitting this year with stride. BRINSUPRI is continuing to be pursued over there. We'll see what their pricing decision is and what that would imply for us. But we have to be mindful of MFN and the policy since it has not been finalized yet is one we just have to hold off and respect until it's been clarified what that's going to look like. To put a finer point on that, in a world where the MFN policy applies only to Medicaid, that's not a big deal. We can manage that. What do I mean by that? If the policy says that your price abroad and very specifically, the second lowest price that you sell the drug outside of the U.S. becomes the price that is applied for Medicaid patients, that's about 3% to 5% of revenue; that's manageable. If they try to apply it to Medicare Part D patients for almost every biotech company and pharma company out there, it would bankrupt the industry. So I don't think it's going to happen, but they are using that as kind of a stick to motivate people to come to some kind of negotiated agreement. And until those proposed agreements are out there, it's just impossible for us to move forward in Europe. So we're watching it carefully. I think we're going to come to a rational outcome here. My concern is that if this -- because it's an election year, you're going to hear a lot of drama and see a lot of fireworks. But I think at the end of the day, reducing prices for certain pockets of patient populations in the U.S. is a probable outcome. It's just not going to be as dramatic as I think people would imagine. And I would just footnote by saying all of those deals that have been done with big pharma, not one of them have been disclosed as an SEC publication, which means not one of them is considered material. So whatever the agreement is, whatever the hype is, nothing has been disclosed. If it were material, if it was going to have a profound impact on revenue, they would have had to disclose it. So that tells you that whatever the hype is, the substance behind these agreements is not that big.

Drilling down a little on insurance coverage, early indicators of payer access and reimbursement hurdles, what percentage of payers have been implementing, like hard implementing the 2-plus exacerbation prior auth requirement? And what is -- can you talk to sort of the discount you're offering to have this removed?

Yes. So what we did was to go to the insurance companies and say, "Look, this is the only approved medicine for this condition. So technically, you have to cover it." We don't need to negotiate with them. We can just insist that they provide the coverage. And there are other companies who have taken this approach historically. We didn't feel that was the right one. So what we've gone and done is offered a modest discount, and I'll talk about what that quantity looks like in a moment, in exchange for helping to shape the policy that they develop, which is patients who have 2 or more exacerbations, attestation by the physician that those have occurred as opposed to summing up the documentation and submitting a...

[ They ] are not paying for removal of the 2 plus, you're just making attestation of the 2 plus?

That's correct. The attestation and then it's the reauthorization of the prescription because one of the techniques that's being employed by insurance companies now is they don't want to be on the record for having denied someone access to the medicine. But 6 months after the medicine is used, they may put additional restrictions on its reauthorization. We are not experiencing that. We have been able to negotiate to avoid that. And frankly, because of the nature of the medicine, it isn't something that insurance companies are going after in our case. But these are the kinds of things you want to think about. And the ability to those policies a little bit in exchange for a modest discount makes sense to us. So that's what we've tried to do. To be clear, we have not done that with every insurance company. There are some that refused the discount that we offered. They wanted much more, and we said, "No, we're not going to do that." So they're going to be following a policy of documenting the exacerbations and documenting the CT scan and submitting that. By the way, that's what we've been doing since the launch of the drug because everything has been through medical exception. Now as the policies are established, some of them will require that going forward, some of them will not. It makes it less difficult if you don't have to provide all that, but it is something we're absolutely prepared to support in terms of companies, doctors' back offices. And many of them have experience with specialty medications like Fasenra. So in that case, they're used to this process. So I don't see it as a break or an impediment in any way.

So part of that -- likely part of the exception process is this idea of CT scans. Now for the plans that took your discount, they're not going to require a submission of a CT read or whatever. But if we think about the plans that are requiring CTs, what percentage are those? Do they need to be recent scans? And how hard is it -- if a patient doesn't have a scan, how fast can they get a scan?

So the temporal component of when the CT scan was taken is less relevant than that there is a definitive diagnosis of bronchiectasis. That's accomplished by a CT scan and a pulmonologist workup. And if that's been documented, then you know the patient has bronchiectasis, that's not in question. It's a very easy thing to read, by the way, from a radiography point of view. It's a tree and bud pattern. And if it's there, it's a definitive diagnosis of bronchiectasis. What's interesting is that for many of these ancillary populations, the COPD and asthmatics, many of them have had a CT scan. But if the request has not gone in to look for bronchiectasis, the radiologist may not call it out. So many of these patients may be sitting out there with a CT scan that shows bronchiectasis, but it just hasn't been diagnosed yet. So there is the ability to retrospectively go back and look at those CT scans and look for bronchiectasis. And we're in the process of doing that in a variety of different ways, trying to support that effort, the use of AI to go back and quickly scan and look for evidence of bronchiectasis is something that some hospitals are making use of. So I think there's going to be an opportunity to look at that and understand it. And I do want to come back to your earlier question because I didn't answer it on the discount that is associated with these planned negotiations. What we've guided to is gross to nets of around 25% to low 30s. Knowing that we are responsible for 20% of the catastrophic coverage in the Medicare population means that right out of the gate, our gross to net is going to be at least 12%, 60% of the population, 20% we have to cover, 12%. So if we're guiding 25% to low 30s, you can get a sense that including the other components of the gross to net discount, we're not giving away that much. Otherwise, the gross to net would be much higher.

Going back to what you mentioned about the COPD and asthma population as we think about that undiagnosed pool that you originally talked about, is that CT reread effort the tip of the spear when you think about 3 years from now, 4 years ago now from when you really start focusing on expanding the diagnosed bronchiectasis market?

Yes. So we think of this as almost two different launches. So the first launch is targeting the 250,000 patients diagnosed today with 2 or more exacerbations. That's a massive market. It's a very easy to go after market. There is nothing else approved. There's not expected to be any competition for at least 5 years. That gives us free rein on that initial TAM. What we're talking about with these comorbid patients is a bigger effort of getting the physicians to increase their index of suspicion, look for bronchiectasis in any COPD or asthmatic patient who is being treated and still has exacerbations because it may be that the source of some of those exacerbations or all of them is actually bronchiectasis, not asthma or COPD. And so we hesitate to use the phrase misdiagnosis or mistaken diagnosis, but there is probably some portion of patients out there are probably some portion of patients out there that have been misdiagnosed because to diagnose COPD is a spirometry test in the office. To diagnose bronchiectasis requires a CT scan. Historically, there's no reason to send somebody for a CT scan if you're going to diagnose bronchiectasis and there's nothing available to treat it. Now there is something available to treat it. So you can look for it. I think the increased diagnosis rates will reflect that over time. And as we shift our attention to that broader population, bringing some of them into the funnel could open up a massive, massive opportunity because the literature right now says somewhere between 40% and 60% of asthma COPD patients are comorbid with bronchiectasis. Just to put that in perspective, we have a $5 billion peak sales estimate based on 250,000 patients that we're targeting right now. If we take 4% of just the COPD market, the low end of that estimate, that's 800,000 patients. That's more than 3x the market we're going after right now. So the upside here for this drug in patients on label and which insurance companies will support is multiples of what we're starting after in the first year. So this is a huge opportunity in front of us, and we're going to resource it accordingly.

So we've got 7 minutes left. We need to touch on TPIP because that landscape has been evolving just in the last 24 hours. And your ENCORE readout, which is for ARIKAYCE, which is your next catalyst. Let me start with TPIP. Thoughts on the competitive landscape in PAH, given the data from [ Tyvaso ] oral treprostinil this morning [ former ] and the conversations around soft mist and potential once-daily Tyvaso, how are you seeing the competitive landscape potentially evolve to time of approval?

So it's still early, and we're getting into the data, but I would just tell you that nothing I saw from this morning's Ralinepag data nor the soft mist inhaler, I think, has any impact whatsoever on the strength of the TPIP target product profile proposition. We're talking about the only medicine that we have that is available or will be available that is once a day that is inhaled, which is the preferred route of administration and which allows you to get to much, much higher levels of the underlying drug, which is the goal of treatment for this fatal condition. We saw absolute best-in-class and best-in-disease PVR reduction data in Phase II last year, better than sotatercept. So this drug is more convenient, appears to be more safe and more effective than any other prostanoid bar none. What is coming out now from [ uther ], I think, is interesting, this soft mist inhaler, for example. That's an attempt to reduce the very difficult problem of cough, but it's one component of the challenge of that medicine. The other components that are challenging are the fact that it's 4 times a day. So you want to use the soft mist inhaler to try and make it easier to take. But what you're doing is you're changing the composition only modestly. I see this as a product that is going to counter detail YUTREPIA, but I don't see it as a threat to TPIP. Why? The underlying drug that you're breathing in is still active treprostinil and your body reacts to the prostanoid, not to the form. So the more severe cough reaction comes from the fact you're breathing in an active drug. It doesn't come from the fact that it's dry or wet in terms of its inhalation composition. So yes, you do see some very transient impact from breathing in dry powder, but it is not sustained. And as we saw in our Phase II data last year, it wasn't even hardly in evidence, at least in our case. The main reason why we don't see a lot of cough with our drug is because it has the 16 carbon chain appended to it. So when you breathe in the drug, it's inert. When you breathe in the soft mist inhaler, the drug is going to be active. You're going to have the same upper airway bronchospasm kind of reaction when that prostanoid is first inhaled, at least that's our prediction. And I will be surprised to see if that is not the case. Regardless, it's still 4 times a day versus once a day, and we're able to get much, much more drug into these patients. And we've already seen the PVR data from last year's study. We'll have more information by the end of this year as we do the open-label extension in the first year. So that will be interesting. We'll have 6-minute walk data. We'll have NT-proBNP...

With the higher dose.

With higher doses in some cases.

What should we expect? Because I think we're watching -- many investors are watching that [ 12 80 ] higher dose come out of that come out of that open label, what percentage of patients were able to get to that highest dose? And what data could we expect that emerges from that?

So I want to set expectations clearly. We did not set up the open-label extension to push patients to higher doses. It is simply that through the open-label extension, physicians at their discretion, should they wish to, can go above the doses that have been...

We heard they wish to. So that's why I think there's a number of patients.

In some cases, they have raised, but we don't have many patients that are at [ 12 80 ]. Oftentimes, physicians will get patients to a level where they're performing extremely well, and they'll just hold them there. And then as the patient declines later on, that's when they'll increase the dose again. And that's why you see the opportunity for our drug to be more impactful because with administration once a day, it's very unlikely that patients are going to miss their dose. If you're taking it 4 times a day, that's a bigger burden. And oftentimes, what happens is they'll skip a dose or 2, and that makes it very difficult for them. But I think the proposition of TPIP and where we are, the open-label extension data, being able to give some additional ideas of what happens as you go up in dose will be very encouraging. I think certainly, everything that has ever been done with prostanoids shows that the more you give, the more patients benefit. The trick is, can you overcome the adverse event profile? And it certainly seems from our Phase II data that we've been able to do that. Indeed, our Phase III study targets [ 12 80 ] is the upper end of the dosing range as opposed to 640, which is what we did in Phase II. And the reason we're moving to those higher doses is because the KOLs and the FDA encouraged us to. So this is not just us trying to push the dose as high as we can go. This is us being pulled into that world. And the best evidence for the perception of this drug as being a real game changer in this industry, Tyvaso right now is approved for PH-ILD. And yet, even though that drug is approved and on the market, we are still able to recruit patients into the PH-ILD study out of the U.S. It's a very encouraging sign. It's early days, but we weren't expecting that.

And last question, I'll ask few minutes. The ENCORE data for frontline, it's only Phase III, could only double your TAM for ARIKAYCE? But what more than -- what do we see?

So it was 30,000 patients is the TAM right now. It goes to north of 200,000 if these data go the way we think they're going to. So it substantially increases the addressable market for ARIKAYCE.

What is good data from ENCORE, especially on that PRO?

Statistical significance on both the PRO in terms of its performance relative to the control arm. And then within group change levels, what percentage of patients show that minimal clinical improvement.

So like a responder analysis within the PRO as well?

Those two, I think, are the most important points. For Japan, it's culture conversion. And certainly for patients and physicians, it's culture conversion.

Even in the U.S.?

Even in the U.S. We've never done a study where we have not won on culture conversion. These patients were recruited at the same time as the ARISE study. The only distinction between these two is that one runs longer. And what we saw in the ARISE study, which was so compelling, is that we were able to culture convert 80% of patients in 6 months. To put that in perspective, it was considered a breakthrough discovery to convert 30% of patients who are refractory after 12 months of treatment. So this is a major advance. If this continues to hold in the ENCORE study, it also sets up the motivation for physicians to treat these patients earlier.

So control is a double dose of -- I'm sorry, not a double dose. It's a 2-drug combination in ENCORE versus the standard of care, which is 3 drug, right? So you're comparing ARIKAYCE plus a 2-drug with the triple combination. What is the delta in culture conversion that you think you need to show versus the double combination for this frontline population, right, which does have the option of triple -- cheap triple therapy? What delta do you need to show for doctors to say, yes, we're going to start reaching for this in frontline?

And I wouldn't draw a hard line, but I would say somewhere in the 15% to 20% range in terms of a delta would be clinically meaningful. I think equally important to culture conversion is durability. And you see the Japanese asking for that specifically as a part of their endpoint analysis. So not only do culture convert, but when you go off drug, do you remain culture converted. And importantly, when you look at ARISE, every patient who had culture converted on the control arm was positive again when next measured. So we are able to provide historically durable culture conversion, which we think is what gives rise to the ultimate benefit to these patients in terms of symptoms, patient-reported outcomes, et cetera. So all of that aligns very well. We're very confident in these data. We think they're going to go well. And we also know that the FDA is encouraged by the success of this drug and considers it a success story and is anxious to see this get expanded into frontline patients.

With that, we are at time. Thank you very much, Will.

Thank you.