O kay. Hi, good morning, everyone. Welcome to day one of our Cantor Healthcare Conference. My name's Olivia Brayer. I'm one of the senior biotech analysts here at Cantor, and really excited to kick off today's conference with Sara Bonstein, who is CFO of Insmed. Sara, thank you so much for being here with us. Yeah, thanks so much for hosting us. Really appreciate it. So a lot's going on at Insmed this year. You guys just came out with a really big update in terms of peak sales guidance. Maybe just talk us through the decision to come out with that update. Why now, and how did you ultimately get to some of those numbers, right? The $7 billion and the $6 billion and the $1 billion. Well, thanks for the question, and again, thanks for hosting us and having us here. Little old Insmed put up $14 billion in peak sales, is our estimate between our three, either commercial or late-stage products. So really tremendous, and our level of conviction is very, very high in those numbers, obviously. Specifically, why did we do the update now? As we go through our own internal processes, we do an annual, we call it our strategic plan every year. We do our annual strategic plan in the July, August timeframe, share that then with the board in August during our strategic offsite with the board. We had all of this new information to share. We had almost a year of launch now under our belt with BRINSUPRI, and while we had a ton of conviction in the $5 billion number that we were able to put out, which was obviously a monster number, we learned more about some of the underlying assumptions. We had shared previously throughout the journey of the launch up to that phase that we were either meeting or exceeding or doing better than our own internal sort of assumptions and benchmarks. You see us pull that through in our revenue model and in the guide that we shared with all of you by increasing from $5 billion to $7 billion. So that's a 40% increase in our conviction in BRINSUPRI. I'll just put a pin in, that is the base launch. That does not account for this sort of secondary launch that I'm sure we'll touch on in potentially under-diagnosed patients that have COPD and/or asthma today. As we think about TPIP, previously, we had a $2 billion number out there for TPIP for two indications. It was for PAH-ILD and PAH. We had put that number out before we even had our phase II data in hand because it was a proven, a known mechanism action. Now with the strength of the phase II-B PAH data, the while small but very encouraging phase II-A PAH-ILD data, and then most recently, the OLE data for PAH. We now had, again, more new information, as well as have made the decision internally, and shared with all of you, to progress into two additional large indications, PPF and IPF. So that update from $2 billion to $6 billion for TPIP reflects all four indications, each of which we believe could be a blockbuster in and of itself. ARIKAYCE, we had always assumed for the success of the label expansion, and that was already embedded in the $1 billion. So, yeah, tremendous amount of revenue potential, and that obviously doesn't take into account some of our earlier stage pipeline. Yeah, maybe we'll start with BRINSUPRI, just given how much focus there is on it. A question that I get asked, and I'm sure you get asked a lot, is why the decision to actually increase from or what gave you the confidence, right, to increase from $5 billion to $7 billion, rather than we'll just get to that $5 billion number maybe faster? Or maybe the answer is both. Yeah. So maybe we'll actually rewind and think through before we launched BRINSUPRI, we were putting out analogs for the best specialty respiratory launches that existed. We looked at OFEV and TEZSPIRE and DUPIXENT and FASENRA, and in their first year of launch, they put up about $500 million to $700 million in revenue. That's what really, really successful respiratory launches that I think we would all sit here and agree have been game changers in their space. As we have now launched BRINSUPRI and put up the very impressive revenue numbers that we have from an actual basis, and have been able to previously had the billion-plus guide for this year, and then most recently updated our revenue guide to the $1.25 billion to $1.4 billion this year. That is double plus what really successful specialty respiratory launches look like. Right? Our execution, the operational excellence that our commercial team has been able to show in the early days of the launch is absolutely tremendous, and you see that being pulled through in the actuals and the revenue guide for this year, and we needed to continue pulling that through in our peak sales estimate now that we have this level of conviction in the launch. Yeah, and you mentioned your launch. Obviously, you guys are having an incredibly successful launch. What are some of the metrics that maybe are tracking ahead of your own internal expectations that are maybe some of the biggest tailwinds that you guys are experiencing? Yeah. So a lot of sort of unsung heroes in this launch. The team has just been kicking it out of the park. I'll remind you, we started disease state awareness for this launch, thank you to everyone that supported us financially to be able to do that, three years before the launch. That has really shown to be successful. Right? This is a first in mechanism, first in disease launch. There was a needed education to set the foundation going into the launch, and you're seeing sort of the fruits of those labors in the actuals. The team that's on the ground executing, educating compliantly on if it's a therapeutic specialist, if it's the field access managers, if it's the case managers, if it's the field-facing medical team, they are all hitting it out of the park with their execution. A lot of, like I said, unsung heroes. The pricing reimbursement and access side of this is going wonderful. We have commented about 90% payer approval. Patients are getting their drug within about a week. Those are very high marks to be meeting. Patients are feeling better. They are starting to get that feedback loop in the physicians' offices and the medical offices. A lot of really strong opportunity there. We are seeing depth and breadth. We are seeing increases in the amount of writers. You saw that continue to increase in our Q2, where we went from about 5,000 prescribers cumulatively to about 6,300 cumulative prescribers from Q1 to Q2. You saw us grow in how many scripts folks had written. Previously, it was about 20% of the physicians had written five or more, and we were able to, while adding new writers, increase that to about 30% have written five or more. Really, really impressive. We still have a lot to go. We now have, if you add up all the new patient start numbers, a little over 26,000 as of Q2, new patients on drug. I will remind you, there is 500,000 diagnosed patients today with bronchiectasis. That is data that is a couple years rear in the facing, and about half of those are two or more. We have just started to scratch the surface on patients that could be impacted positively with this medication, and there is over 20,000 prescribers. About 28,000 prescribers. Again, have a ways to go. We have done really well on all of those metrics, but still more opportunity. You mentioned that that 500,000 number is maybe a couple years old, right? In terms of when you all provided it. I am going to ask a little bit of a forward question, but could that number maybe be bigger than we expected? Could that number maybe be growing over time as awareness and as a new product comes to market? Yeah, I think the number is growing. I think just naturally TAMs grow, and we will kind of walk through U.S. patient population. Obviously that is sort of the straightforward one. Everyone is aware of that. If you look broadly speaking, anytime there is a new product available for a first in disease, you will naturally see TAMs grow. That is something, a dynamic that you will have here. The interesting piece with bronchiectasis, while it is a condition that is life-altering for those that suffer from it is typically not in the sole indication. It is typically not life-ending. You have the unique perspective here where you have incidence and prevalence stacking on top of each other. That will naturally grow our TAM. The other, I think, important piece to highlight is while our label is broad for bronchiectasis indication, the conversations that we had with payers is that two or more exacerbating patient, and we had commented on the diagnosed patients of 500,000. About half of them were two or more exacerbating per the claims data that we had at the time. Naturally, over time, if you have an exacerbation, you are going to have future exacerbations. That's just how this condition works. It is a progressive condition. You will naturally have, over time, your TAM increasing, and you will naturally have, over time, the patients that are fewer exacerbating patients moving into the more frequent exacerbating patients. That sort of organic growth is happening and will continue to happen before we even touch on adding to the top of the funnel for this sort of secondary launch for the underdiagnosed potential for COPD and/or asthma patients. You also brought up just number of prescribers that you guys do have writing scripts. As you think about the launch unfolding from here, what is the priority between depth versus breadth and kind of balancing the two? How many more prescribers do you think you can get to start writing? Then, how do you start to convert some of those initial prescribers into writing that five or more script number that is your top, I guess, 30%? Yeah. We triangulate the data in all the possible ways we can and ensure that our folks' time is being spent as appropriately, compliantly, and efficiently as possible. As you look at that top decile of prescribers and decile one and two, they may have up to 100+ patients in their treatments office. There is a lot of opportunity in depth in decile one and two. Then as you look at your mid-tier, that's where you have the breadth. Because we all live in a data-rich world, we're able to appropriately target time allocation for where we believe we can have the biggest impact on patient. Okay. Very helpful. The other thing that comes up quite often with this launch, and I know last quarter was a big topic of conversation, is just persistence and continuations on drug. Maybe just talk about the dynamics there, how you see those unfolding. It sounds like most people have come to the same conclusion in terms of what they should be modeling. Maybe just help us solve for how to think about persistence going forward on BRINSUPRI. Yeah. So persistence, compliance, continuation, that whole bucket continues to track on what we commented on most recently, continues to track really well. We continue to be encouraged by what we are seeing there. We commented on the access side of the world. I know this was a discussion earlier in the year. There is a difference between clinical trial continuation and real-world continuation across the industry. It is something that we, again, we are celebrating on how well the team has been able to execute on this. So nothing to see here, and you could see in our conviction of being able to go from $5 billion to $7 billion, that this is a drug that we believe is needed for patients and will be one that will be longstanding. As you think about the launch unfolding, you guys have talked about Symphony TRX being a good proxy. I think all of us in this room track that pretty consistently on a Friday morning basis. Is that something that we should still be looking at in terms of launch proxy on a TRX basis? Yeah. I really appreciate the question. We love these types of opportunities to be able to update the market on Symphony. So our most recent public statement had been through the weeks reported through July that Symphony continued to track on a proportionate basis. I am happy to say here, I think there is a couple days left in August that have not been reported. But through all of the reported that has been presented through the month of August, it continues to track on a proportionate basis, and it continues to be up and to the right. That obviously should give folks encouragement on the strength of the launch. We have seen a pretty linear launch curve. I think that continues to track over the last few weeks as well. Maybe I'll ask from an expectation perspective, do you continue to expect your launch to stay linear? At what point in the launch do you start to see that curve, maybe not plateau, but maybe see the slope start to change? Yeah. Obviously, I won't comment anything intra-quarter or forward-looking other than the revenue guide of the $1.25 to the $1.4 that we continue to have conviction on. We're still learning in the launch. It's still early days. We're still going through certain seasons and all those good things. But the underlying fundamentals of the launch are so strong, and the team is executing on all cylinders, and brensocatib is on track to be a top 20 launch of all time. Congratulations- Thanks. ...to you and your team. Gross to net is another thing that I think surprised people to the upside on your second quarter earnings call. Maybe just talk about gross to net, where is it today? How has it evolved over the launch? As you think about gross to net going forward, maybe I'll ask, how have you been able to keep gross to net so low? Do you still have conviction that you can continue to track very favorably from a gross to net perspective? Yeah. We said right from the beginning on, access is really important and appropriative and frictionless access for patient and targeted contract and where appropriate. We've been able to execute on that. As I mentioned, around 90% payer approval. We've been able to have line of sight into what our contracting needs will be for the year. Our original gross to net guide was mid-20s to low 30s. We were able to, now that we have that line of sight, be able to narrow that to mid to high 20s, while still maintaining that positive payer approval perspective. Again, kudos to the team internally on being able to ensure patient access and we'll continue on that front. I won't comment on forward-looking gross to net, obviously, at this point in the year. But our focus will continue to be on frictionless access for patients. Are there additional payer contracts that could start to come online going forward, or at this point, have you all hit the sweet spot? For 2026, we feel like we have a clear line of sight into what 2026 will look like. We will continue to have appropriate conversations in the future with payers if and when appropriate. Okay, great. You mentioned to start, going back to your comment around that $7 billion peak sales number, not including that potential comorbid patient population that you all are hoping to unlock. What does that opportunity set look like as you think about this COPD, asthmatic, comorbid patient population, and what are you seeing in terms of real-world setting? Are you starting to see some of those patients enter the funnel? You have good line of sight into when those patients start to enter the funnel, or maybe when do you expect some of those patients to start to come online? Yeah. This, we believe, could be a very significant opportunity. We are resourcing it as such internally with a dedicated team to ensure that the base launch of the $7 billion plus and the $1.25- $1.4 for the year, all that good stuff, that that base launch is continuing forward without any distraction. This secondary launch of potential under-diagnosed patients, there are 20 million patients in the U.S. with COPD. Between both COPD and asthma, it is over 30 million patients in the U.S. Literature is all over the map on how many of them may or may not be under-diagnosed or comorbid with bronchiectasis, so the literature is not very helpful because it is single digits to north of 60%. But even at the smallest percentage, it is significant potential for more patients being added to the top of the funnel. As I said, we have a dedicated team focused on that. A lot of these are lagging indicators, so we do not believe we will have good line of sight until probably middle of next year. But you have started to see some of the fruits of our labor. You started to see our Suspect BE campaign, which is our celebrity campaign with Ty Pennington. He is a celebrity on HGTV. He is actually also the caregiver for his mom, who has bronchiectasis. It is a look behind the walls because he repairs homes. A look behind the walls and see if you should suspect BE. That is the nature of the campaign. Things like the ATS. We are a sponsor of their initiative, but they are going back through, I believe it is seven or eight of their institutions, to look at electronic medical records of CT scans that are already in their universe to say, c ould there be tree bud patterns? Could there be patients in their universe that already have bronchiectasis that are just under-diagnosed? There is a slew of other initiatives that we have ongoing internally. They are lagging indicators. They will take some time, and so look for an update on that next year, and even at a small percentage basis, it could be meaningful numbers. I would just emphasize that once a patient is diagnosed with bronchiectasis, they are on label for BRINSUPRI. There is no additional clinical work that needs to be done or anything like that. Once they are diagnosed with bronchiectasis, they are on label. It sounds like you are approaching this campaign from both the patient perspective but also the physician perspective, right? Maybe going at it from both angles. In a clinical practice setting, let us say a patient has COPD or has asthma, what are the next steps in terms of actually getting that bronchiectasis diagnosis so that they can get on BRINSUPRI? Yeah. I think the point you made on sort of hitting it from both is so critically important and part of the learnings that we got from the disease state awareness work that we did well before we launched BRINSUPRI and how successful that has been as we look at the true operational excellence from the team on the launch thus far. Continuing those efforts by ensuring that there is appropriate compliance education on both the patient perspective as well as the physician perspective. Bronchiectasis is a pretty straightforward disease to get diagnosed. It is a high-res CT scan. The radiologist has to just know to look for bronchiectasis and provide a diagnosis of bronchiectasis. Unless it is sort of checked off on the script to say, look for bronchiectasis, it will not get diagnosed as such. So there is that education element that is underway as well. Okay. Then for a formal bronchiectasis diagnosis, it is essentially a CT scan, right? CT scan. Mm-hmm. Okay. Very helpful. Then as you think about geographies outside of the U.S., obviously the Japan approval just came through. Maybe talk about what the opportunity set looks like ex-U.S., and then I would love to hear if any updates on plans in Europe to potentially launch. Yeah. To level set to help with models, if you look at precedent launches, if you look at precedent for sort of our geographic territories, you should assume about a 10%-15% ex-U.S. contribution for a product like BRINSUPRI. That's what precedent would tell you. That should be helpful. Japan is an opportunity that we're very excited about for a host of reasons. I do think that the Japanese government has been open to the supporting from a reimbursement perspective. You look at the Asian data population, we don't know why DPP-1 works sort of outsized for Asian patients. That is something that, as an industry, we will all figure out. But the data shows us that it does have a higher efficacy impact on Asian patients. That's very encouraging as we think about the 150,000+ diagnosed patients in Japan with bronchiectasis and what that can mean for that patient population. So that is a pathway. Obviously, we have approval now. We are going through sort of the final steps before we would launch from a pricing perspective and all of those good things. But that's something we're highly encouraged about. I would also just remind you that in Japan, any time a new product is launched, for the first year, there's a t wo-week prescription limit. That's all new products, not BRINSUPRI specific, but also just something to take into account as you're modeling. Europe, again, we have approval in Europe. I think there are separate and different budget constraints in Europe, and so we want to ensure access for patients, and so things like the EMBARK study that just kicked off are obviously encouraging just from an access perspective with those 3,000 patients under that program, and we will look for ways to provide access for patients as best as possible. Speaking of DPP-1, you do have a next generation program. So what are you hoping that that next gen molecule will do differently than BRINSUPRI or maybe even better? Yeah. I know you're also looking at other indications. Yeah. BRINSUPRI is a pretty great DPP-1, as I think we all have been able to recognize. We have studied many DPP-1s in our research lab. We have progressed the first of those, 1033, into IND. That IND is now cleared. The healthy volunteer study is now underway. We will look to progress that in indications starting with RA and then UC, COPD. There will be additional follow-on DPP-1s that you'll hear about next year. We believe we know a lot about the mechanism because of all the great work that the team has done with brensocatib, and our research team had started doing work on additional DPP-1s on the heels of the WILLOW data, which I'll remind you was over six years ago. We are encouraged by what that could look like. I'm not going to go into some of the special sauces on the future DPP-1s, but it's something in our pipeline to watch out for next year and beyond, because they're very meaningful indications that could be sort of the next leg of value creation for this story. Okay, great. Your other meaningful pipeline driver, obviously TPIP, a little more late stage than your next gen DPP-1. You mentioned earlier going from $2 billion to $6 billion in terms of your peak sales trajectory for that drug. Obviously a big jump. I know a lot has changed since when you initially put out that $2 billion number, but maybe just walk us through the opportunity set. You're looking at four different indications currently that are either currently in phase III or about to move into phase III. So how do you think about PAH, PH-ILD, IPF, and PPF? I don't know if there's a rank order or if you can put some numbers around them. Yeah. We have two of our phase III's ongoing. PH-ILD started end of last year. PAH started this year. PPF will look to kick off that phase III before the end of this year, and then IPF will start next year. As you are thinking about revenue contribution, I am not going to break down each one. What I have commented on each one, we believe has the ability to be a blockbuster status. We do believe PH-ILD will be larger than PAH, and we believe PPF will be larger than IPF, as you are thinking about scale. But all very meaningful opportunities, and the data that we have in hand continues to give us a lot of conviction into what that program could mean for patients that are suffering from these very severe conditions. Is that the kind of PPF above IPF and PH-ILD greater opportunity than PAH? Is that because of the population size, or is it because of maybe where you guys think that you could fit in from a differentiation perspective? Yeah, I think depending on which one, it is a little of both. Yeah. Okay. Fair enough. Anything that you can tell us about the trial designs for PPF and IPF at this point? Yeah. PPF, it actually just came up on clinicaltrials.gov, so feel free to go out there and check out through the trial design. PPF, it is about an 800-patient study. Pretty traditional study design. That will be up and running before the end of the year. Okay, great. Any thoughts on enrollment at this point? Maybe I will ask for PAH and PH-ILD specifically, just given that you are maybe starting to track how enrollment is progressing. I hate to ask a timeline question. Yeah, no. Fair enough. But just kind of thoughts on next steps, timelines. I think enrollment progress will be something that investors are really interested in. Yeah. I know it's probably not the most fulfilling answer. We do tend to be conservative, so we have not given specific enrollment timelines. We typically like to have a couple of quarters under our belt of the trials up and running. What I will comment on is both continue to enroll well, continue to exceed our internal expectations, and things like the OLE data are really helpful in sort of medical conversations on sort of the strength of that data and what this program could potentially mean for the patient population. Something you guys have talked about is just the ability to increase your dose and have a little bit more flexibility there. I know you are allowing for increased dose levels, or maybe I shouldn't say levels, but kind of a titration scheme in your phase III programs. Is the hope that you could maybe push the efficacy beyond what you've already seen in your phase II program, or is it really more of a tool for flexibility for physicians and patients? Yeah. Each patient has a different sort of need for how high do they need to go in dose. I'll remind you, the 640 dose, which was the max dose in the base studies for phase II, is 60% more raw drug than available based on the multiple times a day and all that kind of stuff. They're already getting a lot more drug. Being able to have the ability to go up to 1,280 now gives the physician even more of an opportunity. There is a longer titration window in the phase III, is the way it is designed. I think most importantly, in the real-world setting, physicians could have the potential to have the ability to have a drug that they can continue to titrate, knowing that these are progressive conditions and patients are living longer and need an option to be able to continue to titrate up in their dose over time. Okay, great. Maybe just one last question. $14 billion, that's a lot of cash over time. What do you plan to do with it? Yeah, we have a very exciting pipeline, and we will be profitable next year. That is a new day here at Insmed that we will be a profitable company next year, which is pretty exciting. Great. Thank you so much, Sara. Thank you. Thank you.