Good morning, everybody. Thanks so much for joining us today for the twenty seventeen Analyst and Investor Day. My name is Blayne Davis. I just recently joined the team here at Insmed as the Head of I look forward to working with all of you, getting to know all of you. Some of you may know I've been in the field of IR for a number of years and really excited to be here to join such a fantastic team at Insmed and look forward to the future.
Before we get started, let me remind you that today's presentation and the company webcast will include forward looking statements based on current expectations. Such statements represent our judgment as of today and may involve risks and uncertainties that may cause actual results to differ from the results discussed in the forward looking statements. Please refer to our filings with the SEC, which are available through the SEC's website at www.sec.gov or from our website for information concerning the risk factors that could affect the company. The drug referenced drugs referenced in today's presentations are investigational. Safety and efficacy have not yet been established, and there is no guarantee that any of these investigational drugs will be approved by the FDA or any other health authority.
Now I have the pleasure of introducing one of the many reasons I joined to join Insmed, a leader that all of you know well, Will Lewis, our President and CEO.
Thank you, Blaine. Good morning, everyone. Welcome to Insmed's Analyst and Investor Day. Thank you for being here today. As I promised you in recent meetings and presentations, today is about giving you the opportunity to meet some of the broader team at Insmed who have been working diligently for more than a decade to bring a new therapy to market for a clear unmet medical need.
I want to start by observing, as you will see this morning, that the team we have assembled in pursuit of this goal is uniquely qualified. You are an audience of investors and analysts. And as I regularly remind this team, investors focus as much, if not more, on teams as they do on the drugs those people are developing. That makes today particularly significant because you will be learning more about both. Before we begin today's program, I want to frame out the cornerstone elements of our company and spend a moment explaining each of them.
I want to start with our mission. A company's mission should be the sole reason why a company exists and it does not change. Our mission at Insmed is to improve the lives of patients battling serious rare diseases. Our values. Values are what we believe in, and they dictate how we will behave.
At Insmed, we expect everyone who works at the company to evidence these values. These were recently identified by a cross section of our employees who volunteered to identify the values they found consistently in evidence across the company. The unifying theme from these values is that we believe we can make a difference in the lives of patients, and the needs of these patients serve as our compass point when setting priorities and weighing difficult decisions. Finally, our strategy. Our strategy defines the actions we will take to accomplish our objective of maximizing shareholder value and, more importantly, how we will prioritize.
For Insmed, for the near to medium term, this means emphasizing growth over profitability. This means we intend to fully resource our lead program and additional life cycle management opportunities in the most attractive geographies around the world. It also guides us to pursue additional programs in strategically adjacent disease states. We plan to continue to do all of this in a financially responsible way. Today, we will present to you actions we are taking that represent this strategy in action.
There is, of course, a great deal more detail that goes into strategy, but this frames out the essential concept. We are intensely focused as we build this company and have been since my arrival five years ago. These concepts have not changed. Since we began this journey, we have grown from approximately 20 to 200 people. And since the founding of the company over ten years ago, more than $800,000,000 has been invested.
During these last five years, as we have sharpened our focus on NTM, we have been able to build shareholder value. Today, we stand on the verge of potentially dramatically amplifying our track record, transforming into a global commercial organization with the revelation of the data from our Phase III clinical trial and the advancement of our successor products. As we move past this moment and into tomorrow, the key to our continued success will be the talent and dedication of the entire Insmed team, coupled with the financial resources you have imparted to us. I want to thank you for the role you have played and assure you that your trust in us has not been misplaced. We are singularly focused on delivering on our objectives, which collectively will advance the interest of the entire Insmed ecosystem.
This includes patients, the physicians who treat them, regulators, the insurance and payment communities and as a consequence of satisfying these constituents, our investors. In the most basic sense, we're in the process of accomplishing several things on their behalf. We are advancing our lead program for the treatment of refractory NTM and anticipate Phase III data from our global CONVERT trial will be released in September, plus or minus one month. In support of this, we have made extensive efforts to educate the community about the importance and appropriate diagnosis and treatment of NTM. We are advancing a second program, INS1007, into Phase II for the treatment of non CF bronchiectasis.
Finally, we have other efforts underway as well, such as INS1009, but these will not be the focus of today's program. Now let me highlight some of the new information and insights we will cover during today's presentations. For our Phase III CONVERT study, we will share with you some new details, including timing of last patient, last visit as well as new information on the dropout rate. Turning to the precommercial activities, you will hear about the size of the potential addressable market, both here and in other regions around the world, and at a very detailed level, our plans for The U. S.
Field force as well as the cost burden of NTM. Your takeaway from this should be an appreciation of the increased scope of the unmet medical need, our new and detailed understanding at the local level of how NTM is diagnosed and treated and our plans to address it. Beyond the initial target indication of severe refractory NTM, we will also detail two new life cycle management opportunities, which we are very excited about: frontline therapy and post conversion long term therapy. These have the potential to add significant opportunity to treat potentially many more patients than we have previously discussed. We'll then turn our attention to our second main compound, INS1007, our DPP1 inhibitor, and describe in detail our planned Phase II trial in non CF bronchiectasis.
Throughout today's presentations, you will see many new faces, including members of our commercial team, our new Chief Medical Officer and our new Chief Financial Officer. You will also see many familiar faces and hear about the work in which they have been involved. So it promises to be a busy day. With that, let me get right to the substance by introducing to you one of the preeminent physicians in the field of NTM who we are very lucky to have join us today, Doctor. Kevin Winthrop.
Long before Insmed was pursuing drug development in this disease state, he, along with a handful of others, has been devoted to understanding this disease from an epidemiological and clinical point of view that we better understand where the disease comes from and how better to treat it. He is a recognized expert in public health and infectious disease epidemiology with an emphasis in mycobacterial diseases. Doctor. Winthrop has extensive experience treating patients with NTM and non CF bronchiectasis. He has authored dozens of papers on this topic and has been a regular speaker at the global conferences that serve as the forums for greater understanding of these diseases.
Doctor. Winthrop is professor at the School of Public Health and associate professor, departments of infectious diseases and ophthalmology at Oregon Health and Science University, and it is my pleasure to welcome him to the podium. Doctor. Winthrop.
Well, great. Thanks. It's a pleasure to be here. This is not my usual speaking venue. So I want to thank INSIMED as well as everyone here who's invested, I guess, in this whole idea because my colleagues and I have been working hard with patients for decades with very, very little, and it is very refreshing to see some new things in the pipeline.
And it's giving not just us, but our patients hope. And as you look around, these pictures really are perfect. I was saying to Will, like the one about the grandma who doesn't want infect her grandkid. Well, it actually goes both ways. Most of my patients are older and they don't want to visit with their grandkids anymore because they're afraid they're going to get sick from them.
And it really does ruin relationships. And this is a quality of life problem for a lot of people and it's growing in its scope. So hopefully, we'll have some new therapies for these folks soon. So I want to just give a quick overview about NTM or nontuberculous mycobacterial lung disease, and most of it's caused by MAC or Mycobacterium avium complex, which is what is currently being targeted in the Phase III program in Insmed. And I want to give you some sense of what patients go through, what this disease looks like, how we treat it presently.
And then I think later in the program, I'm going to talk again about non cystic fibrosis bronchiectasis or NCFB. That disease goes closely with this one. They go hand in hand. Many people with bronchiectasis have MAC, as we call this. Many people with MAC have bronchiectasis.
They really go back and forth and closely related. So it makes sense to target both of them actually. These are my disclosures. A couple of years ago, had nothing on my slide to disclose, zero because no one seemed interested. And patients would come in really at their wit's end because there was no governmental organization wanted to fund research.
No companies were interested in drugs. In the last ten years, there's just been a whole surge of interest in all sectors. So it's really been nice to see. So what is nontuberculous mycobacterium? So for really old people, they were called MOTT, M O T T, Mycobacterium Other Than Tuberculosis.
Then someone about thirty, forty years ago decided, well, it's kind of like tuberculosis, but it's not. It's kind of like atypical tuberculosis. So they named them atypical tuberculosis. And then more recently, people decided to call it nontuberculous mycobacterium. So the world of mycobacterium is leprosy and TB, and then there's all the nontuberculous mycobacterium.
And actually, some people want to rename these environmental mycobacterium EMs instead of NTM. So hopefully, the madness will stop someday. But the bottom line is they're in the environment. So for those of you who showered this morning, some of you didn't, I can tell. But if you did shower, you showered with these things.
They're in the tap water in New York City. They're in the tap water everywhere. And they love biofilm. And these bugs will shield themselves from bleach in your pipes. They'll shield themselves from antibiotics in the human body within cells, macrophages, immune cells, but also within the biofilm that lines the pipe or the airway.
And in your airways, you just you have a complex ecosystem of bugs and debris that live there, and these guys love to be there with amoeba and all sorts of other bugs. And again, they're really good at hiding, which is an obstacle in trying to treat them. There's over 180 species. Mac's the most common, so really we're just going to talk about Mac today. But there are other important ones that we treat all the time that potentially ALIS, I guess, it's called now, potentially ALIS or LAI or liposomal amikacin might be useful for in the future.
So what is the incidence? This was the first incidence study ever done. We did it recently in Oregon. You can see from MAC, the incidence in the last five years has gone up from four point two to four point eight per one hundred thousand. This is incidence.
These are new cases, and this is in the general population. This is abscessus down here. It's much less common, but much more destructive, and there's really no drugs available for it. The prevalence, if you look at prevalence, so people who develop disease, of course, live for several years. So prevalence is higher than incidence.
People collect this disease. And you can see in the last ten years, the prevalence has approximately doubled. This is an amalgamation of different data sources, population based data sources, Medicare, Medicaid, etcetera. But this is probably accurate where the prevalence has gone from about twenty thousand to forty thousand per 100,000 patient years. Now I'll tell you prevalence is heavily dependent on age.
And you can see this here. These are age groups down below. So in the 50 age group, in my age group, it's very rare. So I don't wake up worrying about this. But in a couple of years, I'm going start worrying.
Age 50 to 59, 60 to 69, etcetera, as you see the age groups march up, you see the prevalence or incidence estimates march up. This is incidence. Again, these are new cases per year. So in 80 year olds, you're looking at about thirty per one hundred thousand new cases per year. In 60 year olds, you're looking more like 10.
You can also see that these are males, these are females. We often think about this disease as a female predominant disease, and it is as people age. But under age 60, it's actually a male predominant disease, very slightly male predominant, but pretty equal. And I'll talk about the two main disease phenotypes in just one sec. Why are the rates raising?
And this is not just a U. S. Phenomenon. This is a global phenomenon. We see it in the epidemiology from Canada, from Australia, from Asia, even in Europe.
Rates are lower in Europe, but they seem to be increasing. One of the reasons rates might be lower in Europe is they don't use as many CT scans as we do. So I think a lot of this increase is a detection bias and that we're just diagnosing it more and more, and we're diagnosing it earlier now, which is good and offers the hope of better treatment if it started earlier. The other issue is we have an aging population. We just have more older people, more older people living with chronic lung disease, they're on immunosuppressants.
They're on other things that are risk factors for disease. And so we're collecting these people in our population so we have more people with MAC. How do people get this? I already told you, you got it in your shower this morning. You probably did get it in your shower.
You breathed it in, but your lungs kicked it out. And in fact, the MAC may hang out all day today until you have your cocktail at five and then you're going to cough because you inhale your cocktail and then something is going to happen, the MAC is going to get kicked back out. The point is it doesn't set up shop in your lungs, hopefully. But for the one in a few thousand people who have an underlying lung disease or for some reason they have a predisposition, it will set up shop in their lungs and start to cause disease. And these are just different routes of transmission, but most of it's from water sources.
There are some people who probably get this from soil, working in the garden, busting open bags of peat moss, etcetera, etcetera. I mean I can tell you where all my patients get their infections from, horse barns, cleaning out their horse stable, things like that. Many of these have been documented. Some of these are speculation and ideas. But in some cases, they've been well documented.
Person to person transmission, I'll just make a comment there. That probably doesn't happen. I mean there's some evidence in cystic fibrosis setting that some of these bugs might go person to person, but it's very controversial. And I actually think probably that doesn't happen, but it's still an open question being investigated. How do people feel?
So some people feel pretty okay with this. And then there's some people who feel terrible. So there's a spectrum just like within anything. Most symptoms include fatigue, chronic cough, shortness of breath, and really the fatigue is huge, particularly in older people. This usually onsets after age 50 or after age 60.
It actually takes five to ten years to diagnose generally. And it's very slow. It's very insidious. And by the time people get diagnosed, they tend to have larger amounts of disease and they just don't feel very good. And it becomes a quality of life issue.
And fatigue and cough and chronic cough and shortness of breath are really big components of this disease. Now again, some people deal with those better than others, but some people are more advanced and some people just stop going out in social situations. Many of these pictures describe how they feel at work or at a symphony or in church or at a party. I mean people just kind of gradually withdraw from things because they're coughing nonstop and people are looking at them like they have tuberculosis. Even though they don't have tuberculosis, they have atypical tuberculosis.
If left untreated, this is just a graphic showing that this was a small study showing that people lose lung function every year at a higher rate if they have NTM. You can see development of cavitary disease, which can be quite destructive and actually can kill you. So people do die of MAC. They tend not to die of MAC like they would have, say, tuberculosis if left untreated, but it does happen. And again, most of this is quality of life diminishment, but a certain percent of people will be consumed by this.
The old word for tuberculosis was consumption. Have you heard of that probably? And the reason why they turned to consumption was because it consumed you, and you felt like you were sliding slowly into the grave. Well, the same thing happens here prior to a less it's less common with MAC, but it certainly does happen. And here's a picture of a woman who was sliding that way.
So this is there's really two phenotypes or two different types of disease. One is associated with COPD and emphysema. So this is actually and that's usually what we see in men, although this is a woman I'm showing you. And she had this nice cavitary lesion in her right upper lobe. This is CT scan.
And actually, the CT, this is the right side. That's the left side. And these are the lungs. The little white dots are the blood vessels, and this is your airway, your trachea. But you can see this is very different compared to this side.
And this is an area that darkness in the middle is air because the tissue has been eaten away by the MAC, and this is a nice cavity here that, if left untreated, would continue to expand, and it would consume her, and she would die. The other type of disease is Lady Windermere disease. We usually see it in women. Lady Windermere was a character in an Oscar Wilde play. She was a tall, thin woman who tend to held in her cough.
And she was very demure and she would do this. And someone about twenty years ago, actually a pulmonologist in Portland, Oregon, where I'm from, noticed that many of the women with this disease look like this. They're tall, they're thin, kind of waffy women. They hold in their cough. And he thought these ladies look like the person in this place.
So he termed this lady Windermere syndrome. And this is really the classic appearance of it. You can tell that this is a very thin woman. She has almost no breast tissue. This is her heart.
She has no fat anywhere basically. Right middle lobe, all this blackness, these are dilated airways. This is called bronchiectasis, which we'll get to in the next talk. But these are dilated airways and all that white stuff is inflammation and MAC. Now I'll also tell you this is like I said, we typically see this in women, but we see it in men too.
Tall thin men, I call them dude windermears. And I have lots of dude windermears or dude windermears, whatever we call them. We have lots of them in our practice. So these are ideas, but we certainly see women that with the COPD form of disease, we certainly see men with the lady windermere form of disease. And I always tell him, like, dude, that dude just looks like a lady.
And anyway, I tried to write an article once that said that, and then the reviewer is like, that's not appropriate. Anyway, he didn't get the rock and roll reference. Treatment guidelines. 02/2007, I was part of a treatment guideline committee. Basically, in that document, it's about 200 pages long.
It was just about 12 of us talking about what we think. It was primarily expert opinion. There's not a lot of data in randomized controlled trial fashion that has been generated with our existing regimen. So a lot of what we write about in this document, how to treat people is based on observational studies, really not the best form of science, but that's what we've had until recently. We've also commented in this document that we have no approved therapies for pulmonary MAC, zero.
And the fact that MAVM is highly drug resistant, so we don't have any drugs even to work with at baseline. We have like four or five drugs, that's it. And none of them are approved. So how do we treat MAC? Well, here's how we do it.
If you have kind of the Lady Windermere former disease, nodular bronchiectatic disease, you either get three times a week or every day you get a macrolide and those are your two choices for macrolides, clari or azithromycin, you probably use these before respiratory infections, rifampin and ethambutol. So this is the triple therapy. I can tell you almost no one likes rifampin. Rifampin interacts with about 30 different medicines out there, if I had to guess, but quite a few blood pressure pills, diabetes pills, pain pills, a lot of other medicines that other people are on. So it's a very difficult medicine to use.
It also makes people fatigued and tired and then there's serious side effects. And so a lot of older people particularly do not tolerate it, which leaves a hole in the regimen, then it leaves you on two drugs. And then ethambutol, the risk is optic neuritis, it can make you blind. This probably happens one in every two hundred or three hundred cases. And it actually really depends on if you use it right.
A lot of people don't use it right and the risk is higher. So and then the GI problems with the macrolide. So just I'm just telling you this because we need new drugs because most of my patients can't tolerate all three of those. And you need to be on at least two, if not three, because we treat with multidrugs to diminish the chance that the bugs get resistant to these antibiotics. So it's just like with TB.
We use four drugs, sometimes more. And the drugs are there to protect themselves and to prevent the bug from developing resistance. So we have a lot of problems with this initial regimen, and we don't really have any other drugs other than this. For cavitary disease, you get the same thing, but then we add IV amikacin. So amikacin is the other drug.
There's linezolid. There's a couple of others with modest to zero activity that we still use. But IV amikacin is probably, to be honest, the most potent drug we have. It's just people can't tolerate more than a couple of months through an IV. It's too toxic.
Generally, we treat people for eighteen to twenty four months. So it's a big deal and it's not that fun. Cure is unusual. So the nice thing about building a practice around these bugs is that once you have these patients, you have them for life. Pretty much unless they don't like me or they keep coming back.
And I need them to come back because I got to keep an eye on them. It's very hard to cure them. And even if you cure them, meaning their cost goes negative and they feel good and you take them off therapy, in three years about half of them are reinfected again. So most of these people battle this lifelong. So if they get this at age 60, they may be battling this for fifteen, twenty, twenty five years, which actually plays into some of the things Will just said in his talk about new treatment strategies with ALIS.
Tolerability, I already told you this. The current regimen we have is hard to tolerate. And again, the side effects, the drug drug interactions, we often lose drugs as we go. So we need new drugs to replace certain drugs in that regimen as we lose them. So the need paradigm, we need more drugs for first line therapy.
Even if we start with those three drugs I mentioned, we quickly lose one or more of them in a large percentage of individuals. And it's not just the refractory patients. So far, Insmed has chosen to do the impossible and study a drug in a refractory group of patients. Actually, I told you not to do this. Remember that?
Yes. This is the hardest group of people to show benefit in. These are people that have had no benefit from a regimen for six, twelve months or longer. Many of these people have been culture positive forever and they're never going to be culture negative. So to grab that group of people and put them on a new drug to see if it works, this is the hardest group of people to study.
So if it does work, great job. If it doesn't work, you should have listened to me. That being said, I think there's a lot of other opportunities here about how to use this drug. I'd be talking about any drug now. This doesn't even have to be ALIS.
Any drug that's showing promise, I mean, we'd all be interested to see if it would be useful in the first line therapy for all these patients, particularly because we lose so many drugs as we go. We need new drugs to put in the first line therapy. The other question is can we shorten treatment? I mean, do you really need to treat someone for twenty four months? Is twelve months just as good, particularly when such a high percentage of them relapse?
So could you use Alice or other antibiotics to suppress people or prevent reinfection? How do we use this therapy not just upfront but long term so that once we stop treating someone, we can actually treat them a little bit and keep them disease free for the rest of their life? These are open questions and hopefully we can study these things as we go. So in summary, MAC lung disease, M avium complex lung disease, it's increasing in prevalence. It's a worldwide thing.
Most of these people have chronic underlying lung disease, I told you. We are actually rewriting those guidelines I mentioned from 02/2007. They will be out in 2018. They probably won't comment on this drug because the data from this trial won't be out before those guidelines are being finished written. But we have updated the document in other ways.
Lastly, if less untreated, MAC lung disease can progress, can kill you, but really it's a quality of life issue mostly. And most of these patients need lifelong or really, really long term therapy. And we're looking for new therapies all the time. So thank you again, Insmed, and thank you investors or whoever you are for being part of this. Because as I was saying to Doctor.
Eagle, who I'll introduce, this is not something we normally think about. We normally think about the companies and working with the companies, but we don't normally think about who's behind the companies. And so it just reinforces to me that this is a big team effort. It's not just the patients. I mean the patients think about the doctors, the doctors think about the company, the company, I guess, thinks about you guys.
I don't know who you think about. But the bottom line is this is a big team effort, and I really thank you for taking part in it. So I'll introduce Doctor. Eagle. Gina has become a friend now because I talk to her every day.
She's probably the most vigilant study conductormonitor I've ever worked with, and she's done a very nice job in that way. So she's been running the Phase III pivotal trials, the two twelve and three twelve. And this is a worldwide trial, which I'm sure she's going to update you on. So Doctor. Eagle, there you go.
So good morning, everybody. And I just want to personally thank everybody for taking time out of their schedule to be here today. And thank you, Doctor. Winthrop, for giving us a very nice background presentation on NTM, which is what I certainly am focused on at Insmed over the last few years that I've been there. If every I'm not sure how many of you actually attended the Analyst Day the last Analyst Day that we had just over two years ago.
But at that particular meeting, I presented the Phase III design. And this is during a time when we were in the study start up activities, and we had not randomized our first patient at that time. So we were really excited about getting the study going. A lot has happened in the last two years, not only from the clinical development point of view, but also, as you will hear from my commercial colleagues, the precommercial sort of activities that have been going on as well. So I'm going to start off by presenting basically an overview of the ALICE clinical development strategy.
And I'm going to pause there because I think everybody has heard ALICE now mentioned a few times and probably wondering who ALICE is. But ALICE is our new acronym for the new established name in very, very recent communication with the FDA. And it stands for Amikacin Liposomal Inhalation Suspension. And this acronym will now replace LAI, previously known as Liposomal Amikacin for Inhalation, exactly the same drug, exactly the same compound, just a different name. And we are all getting used to ALICE.
We think that the acronym is actually quite cute, and I'm sure we could do quite a lot with that when we refer to this compound. But I'm going to take you through how ALIS is addressing an unmet need, and you heard from Doctor. Winthrop that there really is nothing approved. And especially patients who have refractory disease, the medical community believes that these patients are almost impossible to convert to negative. I'm going to show you how we leveraged insights from the Phase II study where we saw remarkable results in that patients did actually achieve negative culture results and how we have used the learnings and all of the results from the Phase II study to actually design the Phase III study for success, which is really what we are aiming to do for the sake of these patients.
We've incorporated discussions into all of our development plans that we've had with the FDA to support an accelerated path to potential approval in the refractory population. And this is actually a very, very important point. And I will describe how we're starting to build on the expected strength of the CONVERT data to guide future development in additional indications in NTM. So I'm going to start with the sort of the basic sort of premise or reason for ALICE, especially ALICE in this therapeutic area. And as you heard from Doctor.
Winthrop, amikacin is actually a potent antibiotic, especially in vitro, as you can see here. So when we look at the aminoglycosides and we look at amikacin, it is a drug that could easily be used to treat these patients because of what it does in vitro. However, it is a very difficult drug to use intravenously, which is the mode of administration that it's formulated for at the moment because of its toxicities. So in terms of ALIS, it contains the amikacin molecule within a liposome. And as you can see there, we have a stylized representation of the liposome where all of the molecules of amikacin within that molecule.
And I'm going to ask you to think about how many molecules of amikacin you think are in one liposome. And if you try and count these, you're going to be way off. But if anybody wants to give me their answer during the break, just come and find me. So we have a nebulized therapy. So first of all, we have a nebulized therapy that contains amikacin, and then we have a liposomal formulation.
Both of these things are very, very important when considering the treatment for diseases of the lung, such as NTM lung disease caused by MAC. The nebulized therapy targets the lung directly, and we know that this is the organ that is infected with MAC. And the liposomes themselves help a cationic charge on the amikacin molecule, help to facilitate delivery into the lung tissue as well as some of the cells, such as the macrophages, which Doctor. Winsrop mentioned. All of these things play an important role in the pathogenesis of MAC lung infection, and the liposomes are an important formulation to deliver amikacin.
The whole goal of nebulized therapy in these diseases is to limit the systemic exposure. IV administration of amikacin, as with all aminoglycosides, is very, very toxic, especially if administered for a long period of time. And this makes it very difficult in the context of a disease such as NTM lung disease because the time in which you have to treat these patients to ensure that you eradicate the organism that hangs around for a very long time, often dormant, you have to actually treat these patients for a very, very long time. And it's impossible to do this continuously with aminoglycosides administered intravenously. So what we know from our PK studies delivering amikacin via ALICE via a nebulization is that we do limit the systemic exposure to amikacin, while at the same time, we deliver high concentrations of the drug and amikacin into sputum.
And all of these things are very important considerations when developing a drug in this disease state. So in terms of the regulatory landscape, this is a brand new disease area in terms of research and controlled clinical trial development. And as you heard from Doctor. Winthrop, they've been treating these patients. He and his colleagues have been treating these patients for many, many, many years.
And now it seems like there is interest in our industry and especially Insmed in the forefront of pioneering controlled clinical studies in this space, which is really, really important and provides hope for both the patients and the physicians. The FDA is also trying to facilitate the development of drugs in this therapeutic area. They recognize the increasing prevalence of NTM lung disease, and they also realize that there are no drugs approved for specifically this indication. In October, there was a patient focused drug development workshop. And these workshops are fairly recent in the history of FDA and drug development, where on the FDA turf convene physicians and patients and industry together with the FDA.
And the whole purpose is, in the rare or the orphan disease state, to try and bring together all of these different groups to set a regulatory pathway that's meaningful with all of the multifaceted input from all the different corners that matter for the development of drugs in these areas. I've attended a few other different therapeutic areas. But this one in particular for NTM, which was the first one, was very, very different in that it was extremely well attended. And it was very, very well attended, particularly by patients and by patient groups. And they had quite a voice at this meeting and throughout the meeting.
They were eloquently describing how they felt and what the disease meant to them and their need their desperate need for more treatments or better treatments. And if you look around the room, as Doctor. Winthrop actually pointed out, we do have artistic representation of what these patients describe how they feel. They have a chronic cough. They have fatigue.
They have a lot of comorbidities. And the whole morbidity that goes along with having NTM lung disease on top of an underlying disease already, the morbidity is quite high. And as you'll see in the presentations that follow me from my commercial colleagues, some of the research that's been done to indicate that not only is having an NTM infection in your lung leads to higher morbidity for these patients, but it also leads to higher mortality independent of that underlying disease. So it is a very serious disease. And it's really great to see everybody from the FDA to physicians to industry actually taking paying more attention and starting to develop new treatments.
The FDA has also participated more recently in the Physician and Patient Conference in May, which was attached to the ATS in Washington, D. C. And also at the IS AM last month. And these FDA representatives are from the infectious disease division that is looking at the treatment for this disease, And they basically convey the same messages in that they recognize that there is an unmet need, there's increasing prevalence and there are absolutely no drugs approved at the moment for this indication. So Internet is right there, pioneering at the forefront of developing drugs in this indication.
We have and as you'll see throughout today, we have a passion for treating these patients. We know we've researched and explored and actually spoken to these patients at various times in the last two to three years to try and get an understanding of what it really is to have this disease and how important it is to really find new treatments to help these patients. And INSIMITA has been has received or has been granted multiple designations, orphan indication, QIPD, fast track status. And in June, after the top line results of our Phase II study, we were granted breakthrough therapy designation, which is actually very important. And this is the Phase II study.
A lot of you have read about the Phase II study, have asked many questions about the Phase II study. But this study really was very, very important and formed the basis of the entire clinical development program from now on. And this study was a study that had patients with underlying CF as well as underlying non CF bronchiectasis. And we looked at two different organisms, MAC as well as M abscessus. So it was a heterogeneous population.
Patients came into the study and were randomized either to receive ALICE added to their standard of care or a matching placebo added to their standard of care. The treatment phase was the double blind treatment phase was twelve weeks. The open label treatment phase was twelve weeks. And then there was an off study drug follow-up period. The primary endpoint for this study was based on a scale, which was the semiquantitative scale, which really wasn't used in any other studies prior to this and wasn't validated.
And it aims to look at essentially mycobacterial burden in sputum. ALIS did not meet statistical significance for this primary efficacy endpoint, although we did see a trend in favor of ALIS. However, what happened in this study was that the key secondary endpoint that looked at a negative culture at the end of the double blind phase, we Alice achieved a p value of 0.003 for this outcome. And when our investigators and clinical experts were told of these top line results from this study, basically, they said, the results have just blown my socks off. And so I think that was an expression from over the pond or something like that.
But essentially, these were kind of like really results that nobody really expected. And this is really the reason why the study was designed the way that it was designed because you've just heard from Doctor. Winthrop saying that why are we studying refractory patients when nothing is going to treat these patients? They're never going to get a negative culture. And what we saw in the Phase II study was that with adding ALIS to their treatment, we did see patients achieve a negative culture.
And this was actually like a critical juncture for the medical community and the development of ALIS. ALIS also achieved the tertiary endpoint for the six minute walk test in this study. And when we look at some post hoc analyses and we look at patients who achieved a negative culture, which is amazing feat according to the medical community, we saw the patients who achieved a negative culture. Many of those patients went on to achieve more than one negative culture or culture conversion by the definition of three consecutive negative sputum cultures. And this was actually the one thing that we saw that was driven by the subpopulation in the study with non CF MAC.
And this is just a graph that many of you have already seen, but I just want to walk you through this. And this is a post hoc analysis looking at the beneficial effect of achievement of three of Alice in the achievement of three consecutive negative cultures or the definition of sputum culture conversion, which is very important because this is what clinicians use in their practice to identify patients who are responding to treatment and to set the actual treatment time line for them. So what we see here is this is the purple line. This is the double blind phase. And these are patients that are receiving ALICE on top of standard of care.
And at each time point here, you see the proportion of patients who have achieved culture conversion. And when we look at patients who achieved culture conversion, we have to wait until we see those three consecutive negative cultures. And then the time at which they achieved conversion is going back to that first negative culture that defines conversion. And that's why we have patients as early as the first time point converting. And then as we progress through the double blind phase, we add more and more patients who have achieved culture conversion.
And then in the open label phase, what we see is that patients that are coming off placebo added to standard of care and starting on ALIS, we see increasing number of patients achieving conversion as well. The study goes to twenty eight days off. So there is one hundred and sixty eight day at the end of the open label and then the twenty eight day follow-up. And the reason why we can't see patients converting past this point is because we don't have enough time points after this to establish conversion and then to come back and define the first negative culture as the time of conversion. So these results were beyond what was expected for this study.
And these results are really what provided the impetus for us to move forward with the development of ALIS and the Phase III study. And the Phase before I go on to the Phase III study, of course, I'd like to just present here the safety data for this study. What we saw were a lot of most patients had an adverse event. Remember, these are elderly patients, and they have a lot of comorbidities and underlying lung diseases. But what we did see was with the introduction of the inhaled ALIS that we did see a lot of adverse events that were predominantly upper respiratory in nature.
So patients did actually experience hoarse voice or sore throat or definitely coughing with the introduction of an inhaled antibiotic. Many of these patients, unlike the CF patients, many of the non CF bronchiectasis patients, nebulizer naive as well. We had patients with so but what we saw with the upper respiratory events is if you go for these events and you go into the open label phase, what we saw was with continued use, a lot of the nuisance or upper respiratory sort of local impact of the nebulized treatment, a lot of those adverse events improved with time. We had patients who had pulmonary exacerbations of their underlying disease, and these we actually saw throughout both phases. And of course, these are events that occur as part of the underlying disease, although we did see with the addition of ALIS that we had a high proportion of patients having exacerbations and bronchospasm as well.
So based on these results, both the efficacy results as well as the safety data from the Phase II study, we designed the Phase III study for success. First of all, we have a more homogeneous population, which is based on the subgroup of non CF MAC patients results that we saw in the Phase II study. We are looking at culture conversion as the primary endpoint for the study, which is a very clinically meaningful endpoint. And we've discussed the protocol with the FDA for potential accelerated approval based on Subpart H for the primary endpoint of sputum conversion by month six. And many of the adverse events that I mentioned, we have a very good understanding of what to expect for our patients, and we built some management things into the protocol as well to enable the experience for the patients as well as the physicians to be as best as we can expect from what we already know from the Phase II study.
So the Phase III study is a global study, and we call it the convert study. At 01/1927 sites globally have screened at least one patient. And as you can see, we're in North America, in the European region and in the Asia Pacific region. I want to actually point out one of the regions or one of the countries that we have included fairly early on in the study sort of start up activities, and that is Japan. And you'll hear from my colleagues that will speak after me how important Japan is in terms of the number of patients that they have with NTM lung disease and especially MAC lung disease.
So we do have several sites with key sort of experts in Japan, and Japan has been one of our most stellar patient randomized per site the whole study. So a main player. We also, prior to going into Japan, we did discuss things with the PMDA because they have special requirements for Japanese specific patients, and we have incorporated the essential PK study in the Phase III study for this reason. So this is a very global study. Enrollment was completed at the end of last year.
And as Will mentioned, we're waiting for top line data around the September time frame, plus or minus a month. And this is the Phase III design. Just to recap this, now the patients are those only with non CF and MAC as the NTM organism. This is an open label study, and patients are randomized two:one to receive either ALICE added to their standard of care or to continue on their standard of care. Although it's an open label study, we are all blinded to the microbiological results.
And so as far as the study conduct goes, this is we're conducting this study in a blinded fashion. So there is a treatment phase. Patients come into the study and go into either arm. And if they are converters, they will stay in the study and receive treatment up to month sixteen, depending on when it is that they convert. Because remember, when they convert, you go back to the first month, that's the time of conversion.
And then the treatment phase, as Doctor. Winthrop mentioned, is twelve months or one year continued treatment while patients have negative sputum cultures. And then we have an off treatment phase, which is another twelve months in which we observe patients to see what happens to them after they stop all of their treatments. The primary endpoint for Subpart H submission is culture conversion by month six. And the sub and this endpoint is the surrogate endpoint for the sub submission for the confirmatory endpoint, which is three months of treatment where we're looking for a persistent negative sputum culture.
And this is what the surrogate conversion is for. It's for patients to continue to be negative even when they stop their treatment. The key study criteria, obviously, patients need to have MAC lung infection, which we ask for them to be positive at screening as well as well as in the prior six months or while they're adhering to at least six months of guideline based therapy. Many of the patients in the Phase II study, you may recall, had guideline based therapy for more than twelve to twenty four months, and hence why they were refractory. And I wouldn't be surprised if we have the same types of patients with long, long treatments coming into this study as well.
Patients need to have radiological evidence of underlying lung disease such as nodular bronchiectasis or fibrocavitary disease. And of course, they need to be willing to remain on standard of care, their oral multi antibiotic oral regimen during the study. We exclude patients with cystic fibrosis, active pulmonary tuberculosis, history of lung transplant. And for this study, we also exclude patients who have isolates of MAC at screening with MICs greater than sixty four micrograms per ml. We don't know this for sure, but it looked like in the Phase II study that patients that had high MICs to amikacin their isolates had high amikacin MICs didn't convert to negative cultures.
So the key study endpoints for a potential accelerated approval, as I mentioned, are the proportion of patients achieving culture conversion by month six. And how what are our assumptions and how have we powered the study? We have ninety percent powered to achieve or to show a fifteen percent difference between the arms, and we assume that twenty percent of patients in the ALIS add on arm are going to achieve culture conversion versus five percent in the standard of care arm. And these assumptions are in line and very consistent with what you've heard from Doctor. Winthrop in terms of these patients actually being a very difficult group of patients to treat.
So quite conservative and also driven by what we saw in the Phase II study. We're also looking at the change in the six minute walk test, time to culture conversion, the St. George's Respiratory Questionnaire and the ED5Q as secondary endpoints. So where are we up to? And we'll be promised that we were going to provide some new information for you.
So I'm actually very, very happy to announce that the last patient has exited their month six visit, and therefore, all assessments for patients for the primary endpoint have now been completed, which is actually a very important milestone in the last couple of years. And in terms of discontinuation rate, I know many of you have always like have been wondering what the discontinuation rate is given the adverse event profile and how sick these patients really are coming into the study. We had based our assumptions on a twenty five percent discontinuation rate. I And can't tell you exactly what the discontinuation rate is because we haven't locked the database, and I'm not a program. But I will say to you that the discontinuation rate is slightly better than what we had expected.
And we don't know all the reasons for that. We do have a lot of the same sites that we're participating in the Phase II study. And as we know that this ALICE, a lot of these patients can be managed through some of the things and some of their underlying illnesses because they are a very sick patient population, and we do need sites that really know how to manage these patients and ALAS on top of that to be in the study to do the best thing for the patients. In terms of overall safety for this study, we have an independent data monitoring committee that has met 7x already, and they're still due to meet more times because the study is ongoing. And they do a very comprehensive assessment of all of the safety data, and they have not recommended any changes to the conduct of the study to date, which is very reassuring for us.
And then we have the three twelve, which is the extension study. So if patients are in the two twelve and they do not meet the conversion, they don't actually become converters by month six, they have to exit the two twelve study. And at that point, patients who haven't converted have the option to sign a consent form and go into the extension study where they receive open label ALICE on top of their standard of care for a further twelve months. We're conducting this study, obviously, at the same sites as the two twelve study. And right now, we have 62 clinical sites that have random or put a patient into the three twelve study.
And we're expecting full enrollment by Q3 of this year. So what are the key study endpoints for this study? This is primarily a safety study, and it affords us the opportunity to study ALIS in patients for twelve months. But obviously, patients that are coming from the two twelve study and haven't converted and have been on ALIS for eight months, and that's when we make the that's when we decide their conversion status is at eight months once we have all of the cultures from month six. So those patients can we will have data, safety data on these patients for up to sort of eight plus twelve, which is up to twenty months.
And in terms of the key secondary efficacy endpoints, we will be doing an interim analysis to provide supportive data for the two twelve if we for submission, where we look at conversion by month six as well as all the other similar endpoints, as you can see on the screen. So one of the most important things about this study and even with the interim analysis is that we will have another opportunity to see patients starting on ALIS for the first time added to their standard of care and looking to see how many of those patients will convert by month six. But we also have patients coming out of the two twelve study who won't have converted and have already been on ALIS for eight months. And then what we'll might be able to see is if some patients need more than six months to actually achieve negative cultures and culture conversion. So this is all very important information, particularly given that we're in a space here where we're really pioneering and we're doing the best we can in terms of assumptions and putting a stake in the ground for endpoints, but we will have a lot of information along with the three twelve study to really show us what's going on with these patients and the interaction of the disease to ALIS.
So this is a very, very important study as well. So as we're coming towards top line results and the end of the study now, many of you have been speculating around what are you going to do if you don't meet your primary endpoint? What are you going do if you don't meet this secondary and that secondary? So we've been doing a lot of thinking about this as well. And I'm just going to sort of lay out sort of what we have been thinking about.
And on the screen here, you can see four different types of scenarios that may actually be the outcome of this study. And each scenario, however, does have the primary endpoint meeting statistical significance. And basically, the message here is if we meet statistical significance for the primary endpoint of sputum culture conversion by month six, then we do plan to file under Subpart H. And the reason for this is because we have to remember what we're filing under Subpart H, And that is a filing that uses a surrogate. In this case, the surrogate is sputum culture conversion by month six.
And that is the surrogate for durability of a negative culture or treatment success three months off all treatment, three months after when you're off a total of twelve months of negative cultures while on treatment. So this is why we feel that if we do achieve this primary endpoint, we are in a position to file for a submission. Culture conversion is actually a very, very important endpoint for this patient population that has an infection with MAC that needs to be eradicated, which is the total purpose of using ALICE in this population. And then moving forward, we're also thinking about future studies, and Doctor. Winterip alluded to some of the areas that he thinks that we still have an unmet need.
And what I want to do is actually just take you through the treatment pathway for patients with MAC and where there may be other opportunities for ALICE. So what we have is once a patient is diagnosed, which we have heard from Doctor. Winterp and you'll hear from my colleagues, can be quite some time, often more than two years from when they actually have symptoms. Once they're diagnosed, then they are initiated on a multi drug regimen. Sometime within the first six months, they are reviewed.
But definitely at month six, they will have a review and a repeat sputum culture, at which time if they're converters, then they will complete twelve months of treatment while their cultures are negative. And if they're not converters at this time point, this is where we if we are successful with the two twelve study, this is where we see ALIS being indicated and helping patients that are nonconverters at this time point. Eventually, all patients hopefully will have a successful treatment and complete their treatment, after which time they stop all their treatments and they're monitored for relapse or reinfection. This is a time period during the treatment pathway where there are absolutely no guidelines for how to actually suppress or keep the reinfection at bay. And we know that recurrence can actually be up to fifty percent of patients in just a few years, and that is either going to be true relapse or reinfection.
So there is quite an unmet need for these patients. And this is an opportunity for ALICE, we believe, where we can add to the treatment of patients after they've been successfully treated to prevent recurrence. And of course, if we are successful in the two twelve study in the most difficult to treat population, the refractory population, there's no reason why we wouldn't want to look at ALICE upfront. Remember, there are no controlled clinical trials for upfront treatment. And Doctor.
Winthrop just went through all the reasons why the current drug regimen is probably not as good as we think it is, given that it's in the guidelines. There are multiple toxicities, multiple drugs. And when you listen to the FDA representatives speak like they have in the last two events that they've attended, they are in favor of even new drug combinations or looking at drug combinations with less overall systemic toxicities. So this is where we feel like we may have an opportunity for the upfront treatment of these patients. So in conclusion, we believe that ALIS has the potential to address an unmet medical need in NTM lung disease.
The CONVERT Phase III study, we believe we have optimized for success on the heels of what we saw in the Phase II study. Positive data from the CONVERT Phase III study may support an accelerated path to potential approval in the refractory population. And we're thinking about the future and the life cycle management of ALIS for additional opportunities such as frontline treatment as well as monotherapy maintenance to prevent recurrence, as I mentioned in the previous slide. And with that, I'd like to introduce Roger Adset, who is our Chief Commercial Officer. Roger joined us since September.
And over the last ten months, he and his team, which he will a very talented team, which he will introduce as well, have been working very diligently on many precommercial activities to help with the potential launch of Alice. Thank you.
Thank you, Gina. As Gina said, my name is Roger Adsett. I'm the Chief Commercial Officer here at Insmed, and I'm really excited to be here today to have an opportunity to talk to you about the opportunity that we see ahead of us to bring innovative therapies to patients with NTM. I'm going to spend a little bit of time talking about the global addressable market for Allis. And then one of the things that I've been particularly impressed with in my ten months here at Insmed is the quality of people that we have working at this company, and it starts from the leadership team that goes all the way down through the organization.
And I'm thrilled to be able to bring some members of my commercial team who I think are extremely talented, and they're going to give some thoughts to you about how they're thinking about this opportunity. We spent a lot of time looking at NTM patients, where these patients are, how we're going to address the market and really think about the go to market strategy that we have that we'll be implementing, hopefully, in the near future, assuming we get that positive data. We have had a chance to interact with some payers. So we had a payer advisory board, and I'm going to give you some information around the payers and how they're thinking about NTM and how they're thinking about the potential with Alice. One of the most important things, if you think about launching a product and supplying manufacturing capacity and the supply.
It's an important responsibility if you have an approved product, particularly if it's the only approved product that you have a continuity of supply to ensure those patients are able to get the product. So I'm going to give you a little bit of an update on the manufacturing capacity. Don Ochiolo, who is our tech ops lead, is also here today. So if you have any specific questions, you can also talk to Don. And then perhaps most exciting, and I know we're very much focused on the initial trial and the initial indication patient pool, but perhaps most exciting is just the unmet need and the ability potentially down the line to think about new treatment pathways, new treatment regimens and the opportunity to help more patients than the initial refractory patients.
So we're in a very strong position at Insmed in that we have global rights for this product. We have not partnered the rights to Atlas anywhere around the world. So one of the first things that I wanted to do upon joining the company was explore what the international opportunity actually looked like. So we know that The U. S.
Is a very significant opportunity, and we'll spend a lot of time going through that today. But we also did some secondary research and taking a look at the literature. And as oftentimes in rare disease, the literature is sometimes a little sparse, and so you should take this data as directional rather than gospel. But what should potentially jump out at you, because it certainly jumped out at me, is if you look at the incidence of NTM disease and diagnosed NTM patients in Japan, so a significant number of patients between one hundred and twenty five thousand and one hundred and forty five thousand diagnosed NTM patients in Japan. That compares very favorably to what we see as the initial diagnosed population in The U.
S. And like I said, we'll walk through that U. S. Opportunity in more detail in just the next slide. If you think about actually then the number of treated MAC patients, that's between sixty thousand and seventy thousand, we estimate, in 2018 in Japan, again, compares very favorably to The U.
S. Market. And between fifteen thousand and twenty thousand refractory NTM patients in 2018 in Japan. That's quite a significant opportunity, again, compares favorably to The U. S.
And in fact, if you look at all those refractory patients, they're more in Japan than the sum of all those other markets we looked at. So Europe and Korea, Canada and Australia, there's a bigger opportunity in Japan from what we can tell from the literature. Now why might that be? I mean it jumps off the page, and we need to think about why that might be. Well, Japan obviously has a fairly significant aging population, and we already heard that NTM sort of faves skews to more elderly patients who more vulnerable to that infection.
There's quite a lot of comorbidities, quite a lot of lung disease in Japan. We also know that we all got a healthy dose of NTM in the water in the shower today. We all know that NTM aerosolizes. And so coastal proximity is a risk factor for developing NTM. And as an island nation, Japan is perhaps particularly vulnerable there.
The other thing we did some primary research in Japan and the other thing we discovered is a lot of Japanese patients will undergo annual physicals, and they get a chest X-ray as part of that annual physical. It's not specifically screening for NTM lung disease, but that would show up and potentially help with that diagnosis. So it may be that they're just better at diagnosing those patients. So with this significant opportunity, we think about how we're going to approach that. And typically, a Western company will look to partner the rights to Japan, and that's certainly something that we're open to.
If we get the right partner and the right terms, that's something that we absolutely explore. But we also benchmark as part of exploration as to what are other companies and other rare disease focused companies who were in a similar time in their corporate life cycle, what did they do and how did they think about these opportunities? And increasingly, it's interesting we saw that some of these companies decided they would hold on to those rights and they would commercialize the products themselves. And if you think about it, it kind of makes sense for a rare disease in the discrete patient population, a discrete prescribing population, the amount of investment that you would need to make to actually commercialize that product is not as significant as if you were thinking about a big primary care opportunity, for example. So in 2018, assuming we get our positive data, we will be putting a very small team opening up a KK and putting a very small team in Japan to really immerse ourselves in the opportunity and really understand if partnering is the right route we should be taking or whether we should be submitting the JNDA ourselves and commercializing ourselves.
Okay. So let's talk a little bit about The U. S. And what we see as our initial opportunity in The U. S.
And for some of you who have been following INSMET for some time, these numbers may look a little bit different. So I want to give you some comfort that we're not introducing new data here. We're actually referencing the STROLO data as the top line there for our input into our funnel as we get down to what we think might be our initial indication. And the STROLO data that you're used to hearing is about 180,000 patients who have at isolate. So they have the bug present.
It may not have developed into a full blown NTM lung disease, but they at least have that infection. And what we've done here is we heard the prevalence is increasing at about eight percent per year. And so we projected forward from that STROLO data to 2018, and 2018 seemed like a reasonable year to assess what that initial opportunity might look like. So between two hundred and fifty thousand and three hundred thousand patients have that NTM isolate. The diagnosis rate and the best available information we have is somewhere between thirty percent and thirty five percent of those patients are diagnosed with NTM lung disease.
That doesn't mean that they're getting all of those patients. There may be more patients that are being missed. The current diagnosis rate is between thirty percent and thirty five percent. So that gives you about seventy five thousand to one hundred and five thousand patients with diagnosed NTM lung disease. Doctor.
Winthrop and Doctor. Eagle both talked about MAC as the most common species of NTM. And so we've got an estimate in here of about eighty percent rate of NTM lung disease that's attributable to MAC, and that's the species that we're studying in our CONVERT trial. That So narrows us down to about sixty five thousand to eighty thousand patients with NTM lung disease caused by MAC. Of those, about sixty percent are treated currently, and doctors have different perspectives on this.
This is slow growing bacteria. And so some patients don't feel too bad, so a doctor may decide to wait to treat those patients, whereas other doctors are a little more aggressive depending on how that patient feels and whether they can tolerate that therapy. But currently, about sixty percent of patients are treated, which gives us about forty thousand to fifty thousand patients. And we estimate around twenty five percent to thirty percent of those patients will not respond to their initial therapy. So that leaves us between ten thousand and fifteen thousand patients with nonresponding NTM lung disease attributable to MAC.
We think that, that is our initial population for our anticipated indication of approving assuming success and approval. Okay. Where are these patients, right? So where do they live? We know we talked a little bit about some of the risk factors, and we know we've done some research.
We know that there's a heavier concentration of NTM patients in coastal regions, particularly in the Southeast. These patients are, as you might expect, they're also located in the population centers around The U. S. But states with oceanic coastlines, particularly in the Gulf States, encompass about sixty percent of The U. S.
Population and account for about seventy percent of the annual NTM cases. So they have a certain states such as Hawaii and Mississippi, Florida and Arizona have a high number of NTM cases relative to the state population size. And that likely reflects a combination of host factors as well as environmental risk factors that make this that population particularly susceptible to the infection. So this kind of mapping really allows us to think about how are we going to deploy our commercial resources, how are we going to make sure that we put effort into education and into commercializing the product assuming approval And how can we do that in the most effective way? And so to answer that question and with more detail on The U.
S. Opportunity, it's my great pleasure to introduce Drayton Wise. Drayton is our General Manager for for ALICE. He is perhaps uniquely qualified to lead this team given his most recent experience. Drayton joined us from Novartis, where he led the sales team that implemented this very successful launch of the Tobii Podhaler, an inhaled antibiotic for treating a rare disease, rare population in cystic fibrosis.
So I'm very pleased to introduce Drayton Wise.
Thank you, Roger. As Roger said, I'm Drake Weiss, and I'm the General Manager of the ALICE program. And I have the privilege of leading not only the global program team but also the commercialization efforts. We obviously, there is a tremendous opportunity for Alice around the globe, but my comments today will be focused exclusively on The U. S.
Market. As my team is fond of hearing me say, once we get The U. S. Launch right, that gives us the confidence we'll get the rest of the globe right in terms of the launches. So as Roger said, I joined the company about three point five years ago.
I'd previously spent fifteen years at Novartis. And I developed a bit of a recognized skill set for launching products. I had the opportunity to launch 12 new products at Novartis. And the one I am, without a doubt, the most proud of is the highly successful launch of Tobee podhaler. And when I was leading the cystic fibrosis franchise as the Head of U.
S. Sales, that was one of the launches that we just clicked on everything, and we got everything right. And that's exactly the learnings that we intend to bring to Alice here at Insmed. So back in early 'fourteen, I jumped at the opportunity to come to Insmed to get the opportunity to potentially launch a first in market product like ALICE that has in a disease state that has such a high unmet need. But over the years, I've had a chance to not only meet the patients within TM, those who are caregivers, those who advocate on their behalf and those who treat them, like Doctor.
Winthrop here. And what has the evolution that I've had over the past few years is the sense of a higher purpose in terms of getting this product in the hands of every appropriate patient who needs it. And I think what you'll see is when a commercial team and an organization is driven by that higher purpose to really make a meaningful difference in patients' lives, we can achieve extraordinary things as opposed to just chasing a number or chasing a goal. And once you see the rest of the commercial team today, I think you'll see a few common themes. Not only do we have that sincere desire to help these patients and be a part of the Centimeters community, we also are driven all by that higher purpose to make a meaningful difference here, and we all thrive on launches.
So like Gina, I had a chance to present to many of you back in 2015 at our last Analyst Day, and my focus during that presentation was an update on The U. S. Commercialization efforts. I'm thrilled today to be able to share with you how far we've come in the past couple of years in terms of our understanding of the market and our approach in terms of our go to market strategy. So today, I'll focus on three key areas: first, the current size of the market then we'll talk about how we're leveraging computer learning and advanced analytics to approach this market.
This is an area that we've committed to being differentiated. This will be a core capability of the commercial team in terms of understanding not only the patient journey, but where these patients are who are currently diagnosed and those who may have NTM but are not diagnosed. And finally, we'll go into the go to market strategy. So one of the first questions Will asked me when I joined the company was how can we gain a high level of confidence with the true number of addressable patients at launch? So the team set out to answer this question by looking at a comprehensive analysis in terms of all data sources.
First, we reviewed the published literature, which has been increasing over the years, not only as Doctor. Winthrop, but many of his peers publishing quite a bit these days, not only epidemiology but also a lot about NTM. So we started there. And what we did was looked at every available data source in terms of the peer reviewed literature. We also partnered with one of the most innovative and leading consulting companies in the space, Symphony Health, who has a robust data set of around 45,000 NTM diagnosed patients around the country.
And we gained a deep understanding of who these patients are and what their journey is like. We also have done primary market research with over 1,000 pulmonologists and infectious disease physicians over the past few years, which is a large sample size when you think about how many specialists are out there. We also did sponsored a comprehensive patient chart record review that's led to multiple global publications. So first, let's look at the literature. Roger and Doctor.
Winthrop referenced the Strollo paper. When you look at Doctor. Strollo, who was published in October 2015, in the Annals of American Thoracic Society, the authors there concluded that there are over one hundred and eighty thousand patients in The U. S. With NTM, and around seventy percent of those are concentrated in the coastal areas, as Roger just showed.
We also said, let's take a look at we have a huge addressable population here for an orphan disease, but also look at the growth rates in terms of prevalence. So what we did was went back and looked at the Aegemian paper, which many people quote, and again, it was in Doctor. Winthrop's section, where he looked at an 8.2% annual prevalence growth rate from 1997 to 2007 in the Medicare population. So again, large patient population growing at an 82.2% growth rate. There was also a paper published at the end of last year, the Donahue paper, again, in the Annals of American Thoracic Society, where they looked at NTM growth rates in the five states where NTM is a reportable disease.
And what they found was NTM was growing at around a 9.9% growth rate. And in that population of patients who are between 50 and 80 years old, it was growing at around twelve percent. So when we look at the published literature, we know there are at least 180,000 patients, and we can confidently say it's growing at anywhere between eight and ten percent a year. So large significant growth rates. Again, we also partnered with Symphony Health, again, a leader in the space in terms of not only their ability to leverage advanced analytics, but they have a massive insurance claims database, anonymous level patient database.
And what we can do there is not only look at the patient journey and understand each of the data points these patients go through from the time they present with symptoms to the time they get to a diagnosis and beyond with treatment, we can really understand what they go through and what the symptoms are that they have. So this has given us a deep understanding of the patient. And again, we've sponsored quite a few studies in terms of primary market research to understand the behaviors, the thought process that these specialists who treat and manage these patients have. So what we did was we went back to Will, and we said not only can we confidently say we think they're between ten thousand and fifteen thousand refractory NTM patients on day one of launch, we can go a level deeper. So Roger just showed the prevalence map at the state level and the national level where it's helpful.
But we also looked and said, based on the claims level database, we know that over twothree of these patients are concentrated in 113 counties. That is tremendous concentration for the orphan disease and allows us to really geo target and have local market plans to effectively launch this product in these markets with a modest field force. So if you know Will and if you've ever been around him, you would not be surprised by his response. He said, That's great work. But keep digging, keep learning, and let's learn everything we can about this market to position ourselves for success.
So that's exactly what we're doing. So not only is there a significant addressable patient population day one of launch based on all available data sources, we think there's a significant opportunity to accelerate the growth rate of these diagnosed patients. What we did, again, working through our patient journey, work with Symphony, we found some key insights into this that really stood out to us. Doctor. Winthrop and Roger and Gina mentioned the fact that anecdotally, it takes years before these patients get to a point of diagnosis.
Our claims database shows that over half of these patients take over two years before they the time they present with symptoms to the time that they get to a diagnosis. And this could be for many reasons. We've talked about the nonspecific symptoms of cough, fatigue, shortness of breath, but it also could be that when they're presenting with these symptoms, many specialists have a low index of suspicion. What does that mean? It means they're not thinking about NTM in the list of their differential diagnosis at the top.
They typically, many of these physicians are thinking about it towards the end. So what else could it be? I thought of everything. What else could it be? And that's when some of these physicians get the NTM.
But let's take a moment and really think about that from a patient's perspective. We've talked about these symptoms such as cough and fatigue. But like Jim here talked about when he described his cough in this picture here, Jim talked about a cough that broke him. Jim talked about a cough that he felt like just shattered his world. And he talked about cracking ribs.
And we've heard that from multiple patients through market research that this is not the typical run of the mill cough that we're used to or other patients with chronic cough. Some of these patients have cough that is debilitating to the point where they can break ribs. When we talk about fatigue, again, it's not the type of fatigue that many of us have experienced over time. This is the fatigue that's been described as disabling fatigue to the point where they can't leave their homes. They can't do the things they want to do.
They can't enjoy time with their grandchildren or take vacations with their family. They are devastated, and they're disabled because of this fatigue. So if you put yourself in their shoes and think about what you were doing two years ago and think about that patient who knew something was wrong, they went to the physician, they presented with these symptoms, and either they went through a journey of meeting physician after physician after physician describing these because not everyone is lucky enough to meet a Doctor. Winthrop on the first pass. Many of these patients, again, take over two years living with these symptoms, such as disabling fatigue and cough to the point of some talk about how we could break them.
We also know the published literature in terms of what the five year mortality rate is with MAC lung disease. So when you think about these two years, every day matters, to the point of Doctor. Winthrop said, the quicker you get to the proper diagnosis, the quicker you can potentially get on therapy and help these patients. So when we set out to gain an understanding of how many of these patients are out there who are going through this journey, Roger talked about if you remember on the funnel slide, we talked about thirty percent to thirty five percent of these NTM patients actually gain a diagnosis, a proper diagnosis of NTM. So working with our claims database, we decided to look and see, is there a better way to look and see how do we know where these patients are, who they may be and who's treating them?
So what we did was leveraged advanced analytics, computer learning, and we took an algorithm of robust sample size of forty five thousand NTM diagnosed patients in this sample size. And we did an inductive reasoning basically to say, okay, computer, these are all the data points. We have over two fifty data points for every one of these patients with a proper diagnosis. What do they look like? And if you apply that to the millions and millions of patients in this database, can we confidently say we know where these other patients are who have NTM but are not yet diagnosed?
So with a greater than 90% confidence interval, the computer came back and the advanced analytics came back. And so they're two:one patients. So it matches the published literature. But there are two:one patients who are NTM likely. And again, what NTM likely means is those patients who, with a greater than 90% confidence interval, have NTM.
They've just not yet gotten to a point of diagnosis for every single diagnosed patient out there. What we also know about these patients is there's high concentration and correlation in the areas where, in those top 113 counties, where they're NTM diagnosed patients. And this will serve as the basis for how we go out and have a very focused disease state education, not only to health care providers to help them raise their index of suspicion, to help looking at these susceptible patients, to help these patients get to a point of diagnosis sooner. But also, we're going out, as Colleen will talk about in her section, and talking to patients now through a very focused effort to help them have the tools and resources to engage their physicians and what NTM is. Could they be a likely candidate for having NTM?
And again, the goal of all of the disease state education and this focused effort is to help these patients who are going through this journey, this greater than two year journey, get to a point where they get a diagnosis sooner and potentially the treatment they need. What we also know is based on all of our analysis and understanding of the market, it's going to be critical to look at each of these local markets. So not only having a national strategy will be critical to our success, having local market plans that address each market dynamics will allow us to maximize the potential of this launch. So when you look at the data that we have, two of the when I talked about it earlier, over twothree of the diagnosed patients and NTM likely patients are in 113 counties. When you look at two of these counties, Hillsborough County, where Tampa is in Florida and L.
A. County in California, they essentially have the same number of diagnosed NTM patients. But when you look a level deeper and say, what is the ratio and how are the physicians doing in terms of identifying these likely patients, these patients who have NTM with a greater than 90% confidence level, but have not yet been diagnosed, how are the physicians doing at identifying these patients? When you look at Florida, the ratio is one:one. So for every NTM diagnosed patient, there's only one likely patient who's working their way through that journey to get to a point of a diagnosis.
So what that tells us, the physicians, the pulmonologists and the infectious disease physicians in Florida, they typically have a higher index of suspicion. They're thinking about NTM more often, and the patients are getting diagnosed quicker. In fact, one of our associates was recently having a conversation with an infectious disease physician in the Tampa area, And they began their conversation by saying, I'd like to talk to you today about a rare disease, nontuberculous mycobacteria. The physician stopped our associate very politely but said, look, NTM may be rare in other parts of the country, but it's not rare in Florida. We see it all the time.
But when you look at L. A. County and you look at the differences there, the ratio is four:one for these NTM likely diagnosed patients. Now that presents us with an excellent opportunity for focused education. But what it also tells us is these pulmonologists and infectious disease physicians in L.
A. County may not be as adept and have a high index of suspicion to find these patients. These patients may go longer before they get to a proper diagnosis, and this is an excellent opportunity for education. So the real key point of this slide, I think, is to show you that not only do we have a clear national strategy, we will be looking at local market plans to identify all the key dynamics in each of these local markets to set us up for success. We're not only looking at the centers of excellence, the top key opinion leaders in each of these markets, referral networks, the influence networks, who the top payers are, who will be developing these plans for each market to ensure success.
So when I last presented to this group back in March, I talked about us potentially targeting around 2,000 to 3,000 specialists, primarily in the centers of excellence, in going out with a very limited footprint. What we found actually through our enhanced learning of the market, through our advanced look at the data and leveraging advanced analytics, we think not only can we go and target the top 2,000 physicians in the country that make up around fifty percent of the patient potential, and that's not only the NTM diagnosed but the NTM likely patients, we think we can go a level deeper into the community. These 3,000 pulmonologists and infectious disease physicians, they account for an additional 20% of the market. As we plan our go to market strategy and we refine our thinking around the go to market strategy, we're going to be looking to target around 5,000 to 6,000 infectious disease physicians and pulmonologists. And these additional targets are not only the physicians who are in the centers of excellence, but they're also those who either are affiliated or have connections through influence networks or different parts being in different parts of the country in terms of close proximity.
So what we've done here is done some market research. And we said, okay, what we need to do if we're going to go beyond this center of excellence approach, and we're going to go into this next level, this next group of community pulmonologists who are treating these patients and infectious disease who are treating these patients who are not only diagnosed but NTM likely, we need to learn more about them. So we've done quite a bit of market research here. And what we found was there's a much greater awareness of NTM in this group than we ever thought. And quite frankly, many of these physicians are already treating NTM and managing NTM patients.
What we also learned is there are varying degrees of index of suspicion. Again, an excellent opportunity for education efforts that we can apply very focused as we prepare over the course of the next fifteen to eighteen months. We also found out that over half of these physicians consider themselves aggressive treaters. And what that means based on the research that we've done is they've said if they have a patient with NTM lung disease, they're going to treat this patient greater than eighty percent of the time. So that gives us confidence that we're able to go not only to the centers of excellence but beyond.
Another thing we've looked at quite a bit is precedent analysis, recent orphan pulmonary launches and how did they approach the market. And when you look at the recent IPF launches, they deployed a very similar strategy. Not only did they focus on the centers of excellence and those top key opinion leaders out there in terms of IPF. They also want to level deeper into the community, and that certainly worked out well for the IPF launches and the highly successful launches that we've recently seen over the past couple of years. So that's exactly what we intend to employ here.
So based on all of this, based on our improved understanding of the market, this increased number of physicians that we intend to target, the confidence we have to go beyond those centers of excellence into those top community pulmonologists and infectious disease physicians who are managing these patients currently, we're going to have a larger footprint than I once guided us to back in 2015. If you remember back in 2015, I talked about the need for potentially 30 sales representatives to go out and approach the market and approach this launch. Today, we've completed our targeting and alignment, and we are very close to finishing up our go to market strategy. Today, we can say we're going to go out with around 70 to 75 sales specialists to focus on these 5,000 to 6,000 physicians who make up greater than seventy percent of all potential for NTM diagnosed and NTM likely patients. Our territories are built to cover 98% to 99% of all the potential, but the focus in the beginning will be on this greater than 70% where these patients are currently.
We've also hired our Vice President of U. S. Sales, Jason Hoyt, who's in the audience in the back of the room. Jason comes to us with tremendous launch experience in orphan diseases. He's recently coming off of the launch at Sarepta, where he led the U.
S. Field force for the EXONDYS 51 launch. He also has deep experience launching multiple orphan products with great success. And he's built the initial field forces not only at Vertex but at Sarepta. So Jason comes to us with great experience, and we're super excited to have him join the team.
We've also clearly defined the roles and the profiles of who we intend to be bringing on to help be the face of the company with these physicians, our sales specialists. What we're looking for here are professionals who thrive on launches, who are coming off of probably orphan pulmonary or infectious disease launches, and they have that sincere desire to help the patients. They share the same passion that we all do to do this with that higher sense of purpose to get this product in the hands of appropriate patients who need it. And finally, we're going to have people who are not only small business owners who have the business acumen to develop these local market plans but also execute them. And they want to win the right way, right?
We're going to have high achievers who win, but they're to do it with the highest ethics and integrity. So hopefully, what I've been able to convey to you today is not only our enhanced and advanced learning of the market, how we intend to approach this market from a go to market strategy, but also how we continue to learn and refine this to the point where when we do get to the point we could potentially get to launch, we're going to be set up for success. What I'd also like to do today is introduce Colleen Silk, who is our Senior Director of U. S. Marketing.
Colleen is going to go through our focused efforts in terms of disease education. And then Rahul Batia will come up, and he will talk about how we intend to deliver on an industry leading patient experience. One of the things I think you'll see is this shared passion, this higher purpose with the team. When I talked about earlier my time at Novartis, what I was most proud of, I talked about the fact that the TOBY POD HALO launch. One of the things I'm most proud of here at Insmed is not only the way we've partnered with the community, we've really connected with the NTM community, but it's also the talent that we're attracting into this organization.
And when you see Colleen, what you're going to see is someone who is a tremendous marketer, someone who at Johnson and Johnson or Janssen was a part, a leader on multiple blockbuster brands. And she also not only is considered a rock star within Insmed, she was recognized in the medical marketing and media magazine last year as a rising star in our industry and someone that we should all be watching. So please give Colleen your attention as we go into our focused disease state awareness efforts.
Thanks, Drayton. Good morning, everyone. As Drayton mentioned in his introduction, we're building a commercial team that really has a passion for launching products. Product launches aren't for everyone. I think they require a specific skill set.
So we're building a team that's incredibly special and one that I'm excited to be a part of. During my time at Janssen, I worked on the launches of Xarelto and Invokana. And what I learned from those launch experiences is the power of deep customer insight in developing a successful marketing strategy. During my eighteen months at Insmed, I'm so proud of the fact that we've executed two disease awareness campaigns, one for health care professionals and one for patients that are based on deep insights of our customers and deep insights of the NTM market. So what I'll walk you through this morning is how we see those campaigns having impact and hopefully illustrate how this focus on the patient and the patient experience is really core to everything that we do at Insmed.
So I think this morning, we've outlined the incredible opportunity that we have to help shorten the time to diagnosis for NTM lung disease patients. We understand the process that they go through on their way to diagnosis. We understand where these patients are, and we understand the emotional pull that this long journey takes. It's been mentioned several times this morning that for some patients, it can take more than two years for them to get a diagnosis. And we know through our analysis that on average, it takes twenty months from the time that patient first presents to a doctor for their symptoms to the time they get an appropriate diagnosis of NTM lung disease.
So why is it so difficult for these patients to
get an appropriate diagnosis? We've mentioned this a few times already, but let me walk you through some of the analysis and some of the findings that we have. So first, like many rare diseases, as Doctor. Winthrop mentioned, the symptoms of NTM lung disease are nonspecific, and they vary patient to patient. From our patient journey analysis, we know that almost half of patients are experiencing at least three symptoms at their time of diagnosis.
And those symptoms are common to many other respiratory conditions: cough, fatigue, shortness of breath. Second, through our analysis, we know that eighty five percent of patients have an underlying lung condition, like COPD or bronchiectasis, at the time of diagnosis. Market research tells us that both physicians and patients may be more likely to attribute their symptoms to this known condition than to suspect that something else like NTM may be to blame. So that means that patients live with their symptoms. As Jan described it, it just became her new normal until a tipping point.
For some patients, that means their symptoms are just no longer tolerable. Or for other patients, it's a loved one who points out the impact that these symptoms have on the patient's life and suggests that they see a doctor. Now even after a correct diagnosis of NTM, patients can experience frustration, even guilt at the length of time it took them to get diagnosed. As Gail told us, she felt like she was partly to blame. So it's these insights that drive the development and execution of our disease awareness efforts to help raise the index of suspicion of NTM lung disease among health care professionals and patients and to help more patients like Gail, Lavinia and Jan.
A picture is worth 1,000 words. We've all heard the expression, and we've all had that experience where we just can't find the right words to describe how we're feeling or what we're going through. But it's a painting or a picture that can stop us in our tracks and make us think, That's exactly how I feel or That's exactly what I'm going through. That's the experience that we're trying to capture through our disease awareness campaigns. We want the audience to stop and feel what it might be like to live with NTM lung disease.
Our health care professional campaign, 1,000 Words About NTM, brings to life the patient experience of living with NTM from the frustration of misdiagnosis to the impact of symptoms on their lives. To create this campaign, we interviewed 12 NTM lung disease patients, and we gave their stories to 12 artists from around the world to turn those patients' words into pictures. So we have this artwork around the room today, and the images that you see from Betsy feeling like a prisoner to her cough or to Frances feeling like she just wanted to surrender to her fatigue. These images resonate with health care professionals, as we heard Doctor. Say earlier, because it reflects what they see and hear in their practice every day.
And in the interest of full disclosure, just want to note, did not ask Doctor. Winthrop to make that comment, but it is appreciated and I think reflects the consistency of the patient experience that we hear through our research as well. So we're incredibly proud of this campaign, and we're proud of the fact that it's been recognized for its creativity, but it's the messages of this campaign that we believe have the most impact. Through our website, ntmfacts.com, our congress presence and other media channels, we're helping to raise awareness of the risk factors of NTM, who is that susceptible patient, the importance of treating to guidelines and the impact of NTM on the health care system and on patients. Our patient disease awareness campaign is called Over and Over, and we launched this initiative on May 19.
The campaign was designed to help the audience recognize that when symptoms like cough, fatigue, difficulty breathing happen over and over and without relief, that it could be a sign that something else is going on. The artwork that you see was based on market research and reflects reflects those moments, those specific moments where patients knew that something just wasn't right. It could have been the embarrassment of coughing uncontrollably at work. It could have been the difficulty they felt getting through a workday because of their fatigue, or it could have been how trouble breathing made it more difficult for them to play with their grandchildren. On our website, aboutntm.com, we provide information seekers with facts about NTM and, in particular, the risk factors of NTM.
We want our audience to understand the risk factors in NTM, the symptoms of NTM and empower them to have a more productive conversation with their health care professional about their symptoms. How are we ensuring that our patient disease awareness messages are reaching the right audience? Now it's relatively easy to target pulmonologists and infectious disease specialists with our message, but finding that right NTM likely patient that Jayson just described requires an understanding of who that patient is, where they live and how they gather information. So let me take you through a profile of that patient we're trying to reach. She's a 65 year old woman with bronchiectasis who's struggling with her cough.
At one time, it was manageable, but now it feels like it's keeping her from doing the things that she loves to do like spending time outside in her garden. She lives in a county with high NTM prevalence and a high number of NTM likely patients like L. A. County. She spends several hours a day online, checking the weather or checking up on family on Facebook.
And while she is online, she still relies on her local newspaper as a source of information. So we've designed this campaign to reach this patient in multiple ways: first, when she's actively seeking information about her health care condition, whether through a search engine like Google or directly on a health care website like WebMD Second, through digital targeting, we can reach these patients when she's online doing other things like checking the weather or checking pictures of her grandchildren on Facebook. And lastly, through a targeted PR campaign, we can provide information about NTM lung disease in her local sources of information. Early metrics tell us that we're successful both in our messaging and our targeting of this audience. In the first six weeks of our website launch, we had more than double the expected number of visitors.
And since May 19, we've had over 200 downloads of our doctor discussion guide from aboutntm.com. And those downloads are coming from states with high NTM prevalence: California, Florida, New York and Pennsylvania. These early results are incredibly promising, and we're very excited to continue to bring information and education about NTM to the market through our disease education efforts. So now to continue the theme of helping the NTM patients along on their journey, it's my pleasure to introduce Raul Batia, our Senior Director of Commercial Strategy and Operations, to walk us through our approach to design and development of patient services. Raul joined Insmed about a year ago this month, and he brings a breadth of experience both from his time as a consultant at McKinsey and ZS and also as a commercial leader at organizations like Novartis and most recently Gilead.
Raul?
Thank you, Colleen. Good morning, everyone. During the twenty years that I worked in the biopharma industry across U. S. And Japan, with hands on launch experience in respiratory and infectious diseases like cystic fibrosis, hepatitis C and HIV, there are two critical success factors that stand out for me: number one, flawlessly executing on a clear go to market strategy with deep understanding of the local marketplace and timely actionable insights.
This is something that Drayton and Colleen touched upon. The second critical success factor is delivering upon a tailored patient experience, which helps each and every patient initiate the treatment and then complete the treatment. This is what I'm going to talk about. This is something that excites me, energizes me. And during the one year that I have been at Insmed, we have made an excellent head start with the expertise that we have within my team and our partners.
And before we dive in, let's put ourselves in the shoes of that NTM refractory patient. Now as a patient, I've been on a long journey. We heard that the median time to diagnosis could be around two years. It took me a while before I found the right diagnosis, before I found the right physician. But I haven't achieved that success in getting rid of my NTM lung infection.
Seventy percent of these patients are greater than 65 years of age. So I have limited income since I retired. And the last thing, above all, I have a serious infection, but I also have a strong desire to return to that active lifestyle, spend the time with my grandkids, spend time gardening, growing tomatoes that I would love to get back to. So as is typical for any rare disease patient, they need support. They need help getting started, the education, which begins in the physician's office, the financial assistance, the training.
And that's not just getting started but also the ongoing reinforcement that helps them complete the duration of treatment that was prescribed by the physician. Our goal is to help set up each and every patient up for success and help them achieve that goal by supporting them at each and every step of the way. The education, the case managers who are working with the patients who are eligible financial support the clinical educators who can train the patients in their home as they're starting this therapy. Now as we start thinking about this, what truly differentiates it, right? There are five things.
If you go from left to right, what are the things that we are doing which are different? The first and foremost is that in-depth understanding of the NTM patient journey. We talked about the robust data that we have. We talked about the market research that we have done. The second is the ownership of the patient interface, which is an intimate point person, And the back office support from our partners, so that is effective and efficient.
The third piece. As we are onboarding each and every patient, how do we quickly do those predictive analytics to understand how are we going to tailor the support for each and every patient, and at the same time, have the visibility on where that patient is on the treatment journey. Fourth, keep it simple. In the end, this is a demographic which is elderly, so we have to keep it simple. It has to resonate with the patient, and it has to be flawless.
And the last thing is how do we collaborate with the patients as we are designing our patient support program? Because collaboration is going to be key to ensure that the end product that we bring to the market meets their needs. So with that in mind, we started doing these advisory sessions in Florida, in California, in Texas, in New York. All of these are the high NTM prevalence states that we looked at. And the goal was to have the feedback from the patients as we are designing this.
Does it work with you? Is it going to fit in your lifestyle or not? And we're going to continue that engagement with these patients between now and launch. Now one such example of that collaboration is reflected in a packaging design. This has been led by Colleen and Nicole and that team.
When we think about packaging, especially in the context of prescription drugs, it has some basic functionality. The intent is to keep the product safe and secure, make sure that when it gets to the patient, it is it has the right information that comes along with it. We wanted to go a step further. How do we start thinking of patients as consumers? How do we deliver enhanced functionality, which not only does what it is supposed to do, which is getting the product safe and secure with the right information, but also help them with their treatment.
What we heard from our patients were two things: number one, ease of use. Reduce the number of things that I need to remember when I'm taking my treatment. I don't want to miss a step. I don't want to make a mistake. The second thing, integrated with my lifestyle.
How do I store this? How do I take it along? How do I take it on a daily basis? So with that in mind, we designed a few concepts, and we tested them with the patients. And based on those conversations, we finalized a packaging design, which, number one, supports the patient by breaking that twenty eight day supply into four weekly sleeves, as you will notice.
And each of these sleeves are numbered, one, two, three and four, keeping it simple so that they can break that twenty eight regimen into weekly chunks. The other thing that you will also notice, there's something else besides those vials in that weekly sleeve. That's an aerosol head. Now the way nebulized medications work, including this one, is that you have an aerosol head which goes in the handset, which converts that solution into a mist, which can then go into the lungs. Now we don't want that aerosol head, that mesh to get clogged.
So we wanted to give some aerosol heads, four, in a twenty eight day supply. But how do we tell the patient that you have to replace one every seven days? Because if you put them all together, they may forget. So that's where the cleverness of the design comes in. And each and every weekly sleeve begins with an aerosol head.
That's a physical cue. That's a reminder to the patient to change it as they're starting the treatment for that particular week. And each of those are labeled Monday, Tuesday and so on. Small things but go a long way. The other thing that the patient said, we want to keep it compact, something that I can take along, and hopefully, we see it reflected in the design.
If I'm going to be traveling to Iceland and Scotland in two weeks, I want to take a couple of those sleeves along. I don't want to miss out on the treatment, but now I'm taking not the entire package but a couple of sleeves along with me. I have some personal experience with a different nebulized treatment. Now this is what my daughter takes. And once in a while, when she needs it, she plugs in that controller into the wall.
It's roughly the size of a loaf of bread. And when it's plugged in, I can hear it from wherever I am in the house. Well, you don't have a big house, but still. I can hear it, right? So when we started speaking to the patients about how do they think about the controller that is going to power this nebulized medication, what they told us, what we want is portable.
We want it smart. It should tell me if I'm missing something or potentially shuts off when treatment is done and something which is quiet. So with that in mind, we identified the right controller. It literally fits in my pocket right here. So this is the controller.
Now this is the controller that powers the nebulized medication that we were just talking about in that package. And as you can see, there's one button. There's one button which switches it on. It has battery. It doesn't need to be plugged in.
And it is something that fits in the palm of my hand. So when I'm going to go to Iceland and Scotland in two weeks, not only am I going take my two weeks of supply, but I can easily take this also along with me. Now that's the level of insight. That's the kind of focus that we have as we are designing our patient experience, which I as well as our team are truly excited about. And we're going to keep it front and center as we approach the launch in The U.
S. And globally. With that, I'm going to have Roger come back.
Thank you, Raul. I think what should probably be coming across very clearly is just the passion and the empathy that this team feels for patients with NTM. Okay. So I'm going to talk a little bit now about the voice of the payer. Obviously, a key constituent and one that we need to pay close attention to as we think about launching this product and introducing, particularly into The U.
S. And we've been having an engagement. We had an advisory board with the payer community. And there's definitely a need for education around NTM. We know that this is not top of mind for these payers.
So we spent some time talking about NTM and sharing some of the information such as what you heard today. And we really asked them and quizzed them as to, are we studying the right endpoint, right? How do you feel about our trial design? How do you feel about our endpoints? And the good news is that they feel that the primary endpoint is a very appropriate endpoint for evaluating the coverage decisions.
So in their mind, you have an infection, and the right endpoint is to look at a quantifiable, reproducible, objective endpoint of eradicating that infection. That makes sense to them if you're thinking about this disease. The secondary endpoints, the things like the six minute walk test and the St. George's questionnaire, while interesting, are not going to drive that coverage decision. They see that as a little bit more subjective and not quite as useful as the primary endpoint.
They're well aware that there are no current approved therapies for NTM and that this is quite a significant burden on the patients. As Doctor. Winthrop said, there's actually been no well controlled randomized trials looking at the therapy. And so they know there's a paucity of treatment options for these patients. So they don't anticipate being overly restrictive in the management of ALIS utilization upon launch.
But where they are really interested in is thinking about other subsets of patients with NTM lung disease where perhaps the unmet need is higher and they can maybe focus on some of those subgroups. So we mentioned that sometimes it's tough for data to be accessible for rare diseases, and I'm very happy that Insmed has been able to actually help to solve some of these gaps and start to do some work. And then some of our health economics team has been working on some data for the first time to really understand what that economic burden of the disease is. So this is first year insurance spending in NTM lung disease. This is health utility costs.
And we looked at a number of respiratory diseases and to understand what the first year cost burden is. And this is from a U. S. Health care insurance database. We can't disclose the actual database, but it's a major U.
S. Managed care database. And this covers the years from 2008 to 2013. And you can see here that NTM lung disease first year cost is about $48,000 to treat these patients. That's right between IPF and PAH with 44,000 and $51,000 two other serious rare lung conditions.
And I also want to mention that this, as I said, 2008 to 2013. So while this is the all in cost, the health utility cost, it doesn't reflect the launch of the two products for IPF that were approved subsequent to the twenty thirteen time frame. But if you recall, the payers also wanted to understand, are there subgroups here that maybe would benefit and maybe we should be looking at for NTM to benefit from the NTM treatment? And so we took a look at, again, at that first year payer cost burden in these patient subgroups. And we took a look at those same serious lung conditions, and we looked at what happens if you have just that serious lung condition and then what happens if you're coinfected, have that NTM lung disease as a comorbidity.
You can see in lung cancer, if you have just lung cancer and then you add NTM on top of that, about twenty percent increase in first year costs by having that NTM lung infection. In PAH, it's nearly 1.8 times as expensive if you have NTM on top of the PAH disease. In COPD, nearly 2.4 times as expensive. And in IPF, it's nearly 4.8 times as expensive to treat a patient with NTM lung infection as well as IPF compared to just IPF alone. So certainly a significant economic burden, particularly if you're adding NTM on top of the other rare diseases rare pulmonary diseases.
Now we're going to be asking payers to make a pretty accelerated decision here. We think that having should we get approval for ALIS in NTM patients, we'd love to be able to get that into patients' hands as soon as possible given the unmet need. And really, when payers think about this, they think about the clinical burden of the disease, and they also think about the disease severity. What's the unmet need here? And frankly, they also think about, okay, if I'm going to pay for a therapy now, am I going to get the benefit from that therapy?
Are the patients going to stick around in my plan? So if I'm paying for the treatment, I also get the benefit of potentially successfully treating that disease. And so within NTM, we know that looking at this database, actually, the patients stay for about five years health plan enrollment. So if you're paying for that disease, you're paying for that treatment, you're actually going to hopefully see some benefit, economic benefit from treating those patients as well. And we know that about eighty percent of these patients actually have a comorbidity.
They have a background pulmonary disease, including, as we just saw, COPD, some of these diseases are high priorities for the payers, to really make an impact on the quality of care delivered to these patients. As far as disease severity and unmet need, up to thirty three percent of MAC patients die within the first five years of diagnosis. And you've got a 2x risk of all cause mortality if you have NTM lung disease compared to population. So a significant unmet need, and this data was just published recently in Europe. So an important factor as payers think about the urgency to cover and make this treatment available to their members.
So I also want to say a few words about how we plan to supply the market. And we've been spending quite a lot of time thinking about this. And one of the reasons is in 2016, 40% of all complete response letters were CMC related. Knowing this, over the past couple of years, we've invested in both the scale and the second source supply. We're in the process of qualifying redundant raw material suppliers.
We have a great relationship with our two partners, Althea and TheraPure, for the manufacture of our bulk drug substance. These separate facilities, one's in California and one's in Canada, are validated, and they're both in production. And the formulation skid is highly automated, and these
we believe, will be able to anticipate will fill our anticipated sales demand through 2022.
Formulation Okay. So what about after 2022? So assuming we get our approval and assuming we get positive data, we'll initiate a project in September to evaluate our capacity and actually expand it to deliver 8x our current capacity from Althea and TheraPure. We aim to have this in place by 2021 so that we could handle the demand and have enough capacity for future sales projections beyond 2022. Rahul showed you the nebulizer.
We are very proud to partner with PARI. PARI is the company that innovated that nebulizer, and they're one of the world's leaders and the manufacturer of our device. As we're thinking about this, I also want to note that we received favorable EMEA feedback on the CMC section in 2016 before we decided to withdraw that file and that suppliers and contract manufacturers are experienced in FDA inspections. In addition, we have both internal and external logistics experience, and we're already testing that through our compassionate use programs in various markets around the world. Okay.
So you remember this from earlier today. I know it's been a long morning. But the funnel, we think we're about 10,000 to 15,000 patients as our initial opportunity for NTM patients who caused by MAC who did not respond to the initial therapy. So we think about this as a funnel. We also think about this as really the tip of the iceberg.
We start with our initial 15,000 patients. But what's so exciting about this, and you heard it from Doctor. Winthrop, you heard from Doctor. Eagle, is just the opportunity, the potential we have to make an impact on NTM patients beyond that refractory population. And we're really being guided here by the science, by the unmet need and by the thought leaders in this space who are telling us about the need for a company to invest and do the additional clinical work, conduct those trials and hopefully gain indications to help patients with NTM disease.
So Doctor. Winthrop spoke about the unmet need for a safe and effective therapy for first line use in NTM lung disease caused by MAC. I think we probably heard today, too, if two twelve is successful, if we're able to convert those patients who are the most difficult patients to treat, who have not responded to that initial therapy, there should be a very high probability of read through from that endpoint into patients who are naive to therapy. And we would be hopeful that we'd be able to put in place a successful clinical trial to prove that and bring an indicated FDA approved therapy to those fifty thousand patients who are currently undergoing first line therapy for NTM lung disease. Beyond that first line therapy and the initial indication, we see the potential to improve care for NTM patients by improving the diagnosis and treatment rates.
So having a safe and effective FDA approved therapy for NTM lung disease caused by MAC may increase the willingness of physicians and patients to treat the disease. And treating the more of the diagnosed population increases the potential patient pool for ALIS. Doctor. Winthrop mentioned M. Abscessus.
So M. Abscessus is another species of NTM. It is particularly difficult to treat and quite pernicious. And this could offer an opportunity for us to do the clinical work and see if ALIS would be able to secure an indication to address this population and expand beyond the MAC infections. I think pulmonologists and the infectious disease specialists are actually pretty well informed about how to treat diagnosed NTM once they're diagnosed.
But Drayton talked about this. The index of suspicion is quite low. And this is perhaps not surprising. I think when doctors are trained, if they hear hooves, they're trained to think about horses. They don't necessarily think about zebras.
But maybe what we should be thinking about is if we could increase that education, if you're living on the same Serengeti, then maybe you should be thinking a little bit more about zebras. Or maybe if you're living in Los Angeles County, you need to be thinking more about these zebras because the disease may be not quite as rare as you think it is, given the information that Drayton had shared earlier. So we estimate that up to three hundred thousand patients have an NTM isolate. And we know that not all of those patients are going to progress to NTM lung disease, and not all will have MAC. But using Symphony's medical database and thinking about those NTM likely patients, it seems like potentially there's two undiagnosed patients for everyone who are currently diagnosed.
And then we also talked about a potential maintenance therapy. Doctor. Winthrop mentioned that there's quite a high reinfection rate, so up to fifty percent, I think, over three years is what you said. And so obviously, if the patients are going through their therapy, and I took this from Gina's from Doctor. Eagle's presentation, they're going through their therapy.
We know that based on guideline therapy, you do the culture conversion and then another twelve months of potential therapy after that. So that gives you up to eighteen months of therapy for those culture conversions. So we know that the NTM, the underlying conditions, the risk factors, you get that reinfection rate. So maybe we should think about is there a better way to keep these patients from reinfection. Maybe they don't have to go through and repeat the acute therapy if they get that reinfection and go through that whole burden of all those medicines again.
Maybe if we think about this a little differently and we reduce the frequency of our administration of Alice's monotherapy, maybe we do it three times a week instead of a daily therapy. Maybe we do it Monday, Wednesday and Friday, you take the weekend off. And potentially, if we could prevent that reinfection,
I think that would be
a great boon for patients to keep them healthy and keep that NTM lung disease at bay. So I'm going to bring it home here for you guys. So I think what I'm particularly excited about and what I want you to remember is that our priority markets are The U. S. First, and you should get a real sense of how we're focusing on that opportunity and preparing that go to market strategy.
We're building that in-depth knowledge around the NTM patient, where that opportunity lies and how we're going to implement our strategy. We're building out our U. S. Commercial team significantly, and we plan to accelerate that post OUT-two 12 convert trial results, assuming we get a positive outcome there. We're developing that deep understanding of the NTM patient and their unique needs relative to the disease, and we're being thoughtful about how we can support a positive treatment experience for these patients.
In Japan, we will explore all options available. We believe that it's a substantial opportunity for us, and we'll begin to put feet on the ground in 2018 to become immersed in that market and prepare to launch ourselves as well as understand what partnering opportunities may be available for what appears to be a very significant market. We've not spent a lot of time on Europe today. As I promised, we did more in-depth view on The U. S.
Market. But I do want to mention we have a modest about we have about 20 people in Europe, very experienced commercial team, and we're going to invest commensurate with the opportunity there. We're working on a disease awareness there and understanding what that market looks like. Again, we feel we can cover that discrete pay population of prescribers with a relatively modest commercial footprint. And then I think perhaps most exciting from my perspective is how we really are just at the tip of the iceberg, that we're hopefully, we can bring an option and get that first indicated therapy for patients with refractory NTM disease.
But there's a whole world of opportunity that we'd be able to make a major impact on the lives of patients, and we're particularly excited to continue to work and explore those possibilities with the physician and the treating community. So we did run a little long. So we had initially anticipated a fifteen minute break, but we're going to shorten that just to ten minutes. So if I could ask you for ten minutes to just go refresh yourselves, and then we'll reconvene about the top of the hour, and we'll go to the next part of our session. Thank you very much.
Hey, everybody. We're going to try to get started in the next couple of minutes. So if everybody could take their seats, that'd be great. We're just waiting for the next speaker. So give us just
a second. It's not me.
Great. So we'll get started with the second half. Thanks again for everybody's attention and focus this morning. Hope you found the presentations informative and helpful. We're going to head into the second half prior to getting to the Q and A session.
So we have a couple more presentations, and then we'll go into Q and A. So I'd like to bring back Doctor. Winthrop, who's going to come up and talk about non CF bronchiectasis. Thanks so much.
Okay. I guess the break is over. Slides are coming. Okay. So NCFB is the term that people are using these days.
Some people say BE, bronchiectasis. I don't know. The whole point is you have bronchiectasis, but you don't have CF because cystic fibrosis is kind of its own thing. People with cystic fibrosis get bronchiectasis, but then there's all these other causes, which I'll go through in a second. My disclosures haven't changed, although I just in the back.
Let's see. What is bronchiectasis? So this is a difficult word to pronounce. For patients, it's often a confusing term. I'm always surprised how many patients come to me who have extensive bronchiectasis, yet they don't know what they have.
And it's either because the clinician didn't tell them it was called bronchiectasis or didn't explain to them. They often say, Oh, I think I have bronchitis, but it's really different than bronchitis. Bronchi, ectasis bronchial bronchi is basically the Latin for tube, and ectasis is Greek for stretched out. So it's literally a stretched out air tube, that's what it is. There's this two edged sword and vicious cycle that I'll go through in a second, but here's a normal airway and here's a stretched out airway.
And that airway gets stretched out because of the biofilm, all that gunk I talked about lining the sink pipes in your house. Well, the same thing happens in these airways. You get gunk, and this is biofilm. It's organisms. It's particulate matter.
It's things you breathe in every day that get stuck there and build up. And eventually, this inflammation that becomes chronic causes this airway wall to dilate and to thin, and you lose cilia, which are the small hairs that are present on the inside of these airways that beat one direction and help you efflux things after you breathe them in. So these processes break down and the airway becomes chronically inflamed and dilated. So there's a normal airway. It gets more cylindrical, eventually bigger and bigger, then it looks like a sack full of grapes.
So this person here has cystic bronchiectasis, not cystic fibrosis, but bronchiectasis that really has reached kind of end stage where these are very large dilated airways. And then this is an airway here that kind of looks like this. It is thickened and inflamed and it's full of mucus. Sometimes these things plug up and you just see the solid mucus, which is what you're seeing right there. This was described decades ago as a vicious cycle.
Some people say vicious circle, cycle, circle. I was at a meeting in England a couple of years ago where these two English guys sat up and debated whether it was a circle or a cycle for thirty minutes, and that was when I decided I was glad I was an American. And anyway, the bottom line is, no, we're all friends. We're all friends. So the bottom line is that this is a vicious situation.
That's what I call it, vicious situation. Because what happens, you get the inflammation, it destroys the airway. You build up all this mucus, which promotes bacterial colonization because you're breathing in things every day. Many of those bugs just end up getting stuck there. Sometimes they do nothing, but sometimes those bugs can be very inflammatory like Pseudomonas or like MAC or like H.
Flu and some of the other bugs I'll mention. Then you recruit neutrophils in white blood cells to the airway to fight those infections. Those that process promotes more inflammation and tissue damage, etcetera, and it just goes round and round. So I'll just say that there are opportunities to break this cycle. One is you stop breathing in things.
That's not really an option. The second is you target the bacterial colonization or maybe you target the inflammation itself, and maybe you help remove the mucus that traps many of these things. So this is the basis for our therapeutic strategies, which I'll go over in a second. Non CF bronchiectasis. So again, CF causes it, but in the non CF side of things, you have a long list of causes.
And the number one cause is idiopathic. Idiopathic is a Latin word for meaning we don't know what it is. And there's a lot of things in medicine that are idiopathic. And if you tell a patient that's idiopathic, they think you know something about it, but you actually don't. Chronic lung disease, COPD, others, prior pneumonia, actually post infectious causes, this is a big cause actually.
A lot of people I see come from areas where there's TB. They try to have TB when they're little kids, and TB destroyed their airway in some areas, so they have bronchiectasis that then sets them up later to acquire organisms from the environment like NTM, like MAC. There are some of these rare inherited diseases, alpha-one antitrypsin disease, primary ciliary dyskinesia, some of these other things. Actually, rheumatoid arthritis is not rare at all. There are a number of autoimmune diseases or inflammatory autoimmune diseases that cause airway inflammation and eventual bronchiectasis.
This is kind of looks like sink pipe. This is a good drawing. This is your sink pipe full of biofilm and mucus. And this is actually meant to represent, I think, the undulating flow of this disease that you sometimes have very mild disease, but it can undulate and you get exacerbations. And a lot of people have mild disease for years, and then they progress to having moderate or severe symptoms.
And people oscillate between this. They may have a couple of good months, and then they have a respiratory infection, take antibiotics for a couple of weeks, then they feel pretty good, then they have another exacerbation. And it's this repeated exacerbation in this cycle that just causes gradual decline in lung function. And those areas of bronchiectasis then spread along the airway and then, of course, other airways can get involved through time. The epidemiology is similar to NTM in that it's increasing.
It affects 40, 50 year olds and up. It's more common in women than men, very similar to NTM. And in fact, these two entities go hand in hand. I already told you that. About ten percent to fifteen percent of people with bronchiectasis will get NTM at some point in their life.
And among those with NTM, on the flip side, probably sixty percent, seventy percent, eighty percent of them, depending on what age group you're looking at, have bronchiectasis. So they go very closely together. It makes sense to target them both from a company standpoint. And here's the curve. This is women.
This is men. This has gone from two hundred thousand to three hundred thousand per 100,000 to about double that in the last seven or eight years. Why? Again, same reasons I told you for NTM. We're scanning people more.
We're discovering it more. There's a detection issue here. But we also have longer living people and more people with chronic problems that set them up for this. What bugs are we interested in? These folks acquire a number of bugs as they go along through life.
The gram negative bugs, Pseudomonas is the most interesting bug in terms of causing the most debility and most inflammation and is often the target of our inhaled antibiotic strategies. But a number of these other bugs are also very important, particularly H. Flu, alkalinity, stendotrophomonas, a lot of my patients have these organisms. Gram positive bugs, atypical pathogens, we talked about NTM. Nocardia is something also we're seeing more and more.
Aspergillus typically doesn't invade lung tissue in these folks, but it can cause a hypersensitivity syndrome, which we often treat with prednisone. And then when you're on prednisone, you're at much higher risk for MAC and problems from some of these other bugs. So some little vicious circle. And coinfection is really common. Just to mention, a lot of people have two or three of these things.
And as they go along in life, they just acquire more and more and potentially get more difficult to manage. It'd be nice to have a drug that targets a number of these. Amikacin does. There are several others that also provide gram negative coverage but also mycobacterial coverage, etcetera. Chronic colonization is a problem because what it does, and this was James Chalmers is a colleague in England, and they've very nicely shown that these issues here, mortality, your number of exacerbations, your hospitalizations and your quality of life are all worse if you're colonized with one or more of those bugs I just mentioned versus if you're non colonized.
They also looked at neutrophil assays activity, really markers of inflammation, showing that, that predicts your future risk of exacerbation as well as your underlying disease severity. So there are reasons to target the colonization of these patients. Currently approved therapies, you think this might be a built slide, but actually this is it. And I like to show it. So if I press the button, we'll go into the next slide.
Anyway, the point is we have no currently approved therapies. So again, we're constantly working with patients in the industry looking for potential opportunities to develop therapies. These patients need something. What do we do currently? We work on airway clearance, as I mentioned.
Some people hang upside down on a trapeze bar. It's not the easiest thing for a 75 year old to do. I don't recommend it. Other people have their husbands pound on their backs or wives pound on their backs. There are airway clearance devices, Ocophila valves, things you blow into that help you mobilize sputum and remove sputum.
Exercise is actually the best thing to do. Some people are too debilitated to exercise, of course. It's hard to go run through miles for some of these folks. But I think exercise is a real, real key to managing this condition. Targeting the airway with anti inflammatory therapy, either steroids or antibiotics.
And again, usually, we're thinking about antibiotics to not just treat an exacerbation that's happening, but hopefully keep the colonization level down and prevent exacerbations from occurring. Lastly, sometimes we do lung resection in these individuals. Lung transplant is very unusual, does occur sometimes. So our clinical objectives of therapy is really number one, make the patient feel better. That's usually our objective for most things we're treating, particularly if the condition is not curable.
So once that damage occurs, once the eptosis occurs on the bronchial, you can't reverse it. It's just damaged. So you're not going to gain that function back. All you can do is try to keep the damage where it's at and keep it from progressing. And if you can decrease inflammation and decrease the sputum, which sometimes means getting rid of bugs or at least controlling the pathogens, you can mitigate the progression of lung damage and you can help people feel better.
Lastly, there's the cost consideration. These folks are at much higher risk for death due to pneumonia or to be hospitalized for respiratory infections and prolonged IV therapy, etcetera. So there are cost considerations long term. We have had a hard time with some of our antibiotic therapies. And we have studied a number of these.
I'll just mention several of them very quickly. Most of these studies have looked at time to exacerbation or the frequency of exacerbation over a year. We kind of built a lot of these studies based on what we've seen in CF, where these studies have been shown to be effective or these therapies have been shown to be effective. However, CF is very different than non CF, and I think that's something that's a lesson learned that you can't really look at CF and do this. Similar to with NTM, you can't necessarily look at TB and do NTM work.
They're different entities. And so in terms of no improved inhaled therapies, there have been a number of RCTs, colistin, estrenum, gentamicin. There is efficacy shown with gentamicin, but no one has gone forward and developed that. Colistin and Estrinim, if you look at that data carefully, there is efficacy. It's just those trials didn't hit their primary endpoints for a variety of reasons.
There are two recently large completed large Phase III programs from Airdyme and Bayer, both with inhaled cipro. And these also show efficacy, quite a bit of efficacy, but also have failed to fully hit their primary endpoints, and I'll show you that in a second. Lastly, there is some data that is positive with macrolides, using macrolides as suppressive therapy. You just take it every day, it keeps the inflammation down, keeps the bugs down and will decrease the risk of exacerbations. But I'm going to tell you this right now, there's a problem with macrolides suppressive therapy because of the high rates of NTM or MAC you see in these patients.
So you can't put these patients necessarily willy nilly on macrolides because if they have MAC or if they get MAC, then they'll get resistant the macrolide will get resistant or the bug will get resistant to the macrolide rather. So you have to be really careful using this in this population. Here's the Iridyme top line data that was just presented at the American Thoracic Society. And they did two studies. You can see three and four.
They were called Orbit. This is the pool data between three and four. And this was in all severity outcome. This was just in those requiring antibiotics. And you can just focus on A because the same thing was seen in both strata.
But the bottom line is in ORBIT four, they showed a statistically significant reduction. The hazard ratio was 0.72, p value 0.03. It means patients on the drug were about thirty eight percent less likely to have an exacerbation. This is a significant result. For ORBIT-three, you can see the hazard ratio was 0.99.
There's no difference. And when you pool them, it almost hits statistical significance. The same problem down here when you had a different pool of patients or different outcome definition. But the bottom line, again, you saw a significant result in OORBIT-four but not three necessarily. Same thing with the RESPIRE program from Bayer.
This is just RESPIRE one. And RESPIRE two showed slightly different results. In RESPIRE one, everyone got very excited because the people on Cipro on a fourteen day on and off schedule had a significant reduction in exacerbations. This is a survival curve. So this is time here.
And as you go through time, basically, this is the percent of people that have not had an exacerbation yet. And you can see it's much greater here compared to the placebo. The Cipro twenty eight day on and off arm actually was very similar to a fourteen day, but when compared to the placebo arm, it narrowly missed statistical significance. So you can see the numbers here. The fourteen day on and off was zero point five three, so almost half the exacerbation rate.
And the twenty eight day on and off decreased at almost thirty percent, but the p value wasn't quite significant. Now in RESPIRE II, those results were just also presented. And what they saw was something slightly different. The twenty eight day actually looked pretty good compared to placebo, but the fourteen day didn't look as good as it did in this trial. So overall, again, there's a lot of efficacy here, but it didn't quite hit its primary endpoint in both studies.
So in summary, the prevalence of non CF bronchiectasis is increasing. Hopefully, kind of educated you about what it is. It is kind of a magical term and a poorly understood term. And it is as debilitating as NTM. They go hand in hand.
A lot of it is about quality of life and chronic cough, repeated use of antibiotics, decreasing lung function and being unable to do the things in life you want to do. And it's not just walking to the supermarket. There's a lot of things. You don't go to the symphony anymore. You don't have sex anymore because every time you lay down, you start coughing your head off.
I mean that's not in any of these pictures. But that's the kind of things my patients tell me. And it's a big deal. It really does impair people's quality of life in many ways that we can talk about and not talk about. Anyway, the recent inhalational antibiotic therapies, I think there's efficacy here, but no one's really designed the right trial yet.
We haven't lucked out. I don't know actually, I have lots of thoughts as to what the reasons are. There is room for new strategies, which I think Insmed is going to talk to you about their strategy. But I think targeting inflammation is the key. And whether you reduce inflammation in one or other ways, it may not matter.
In the end, you're going to reduce the risk of exacerbation and make people's quality of life better. So with that being said, I think I'll introduce the next topic or person, looks like Doctor. Sullivan is up, to tell us about their new inhibitor and new program.
Thanks very much for that talk, Kevin. Was wonderful. Good morning, everyone. My name is Gene Sullivan. I'm the Chief Product Strategy Officer at Insmed.
That's a newly created role at Insmed, and I think it's a reflection of our growth maturation as a company. In my new position, I'll be focusing on development opportunities, either the ones that arise from our research group internally or ones that come from external sources. And I'll be helping to craft the most efficient and effective development programs for our products. As some of you may know, I'm a pulmonologist, and I have both academic and industry experience. And also, I previously served as the Deputy Director of the Pulmonary and Allergy Division at the FDA.
I'm very excited to be serving in this new role. I think it's going to allow me to capitalize on my particular expertise and interest for the benefit of the company. So for the next ten minutes or so, I'm going to introduce you to INS1007. 1,007 is an NME that we in licensed from AstraZeneca in 2016. At AZ, the molecule is known as AZD7986.
This is an orally bioavailable inhibitor of the enzyme dipeptidyl peptidase one or DPP1. Also want to note that in the scientific literature, you'll sometimes see DPP1 as referred to as cathepsin C. Those are interchangeable terms. But DPP1 is the enzyme that's responsible for activating the serine proteases in the neutrophil as it matures in the bone marrow. I'll say a little bit more about these neutrophil serine proteases in a minute, But we believe that 1,007 has promises has promise in diseases in which neutrophilic inflammation plays an important role.
And as you heard from Doctor. Winthrop a moment ago, that's certainly the case for a non CFBE. I use the E at the end.
Go figure.
So this figure illustrates the role of DPP1 in the neutrophil as the neutrophil is maturing in the bone marrow. The neutrophil serine proteases are shown here. They are neutrophil elastase, proteinase three and cathepsin G. They're initially formed in an inactive state. And its DPP1 is the enzyme that accomplishes the modification necessary to then render them active by removing this N terminal dipeptide.
Once that's removed, these are now active proteases, and they're stored in the neutrophil in the so called azurophilic granules. So this slide illustrates the action of 1,007. It blocks the activity of DPP1 and thus prevents the activation of the NSPs. I want to take a minute here at this point to contrast this mechanism of action with that of another related class of drugs, the neutrophil elastase inhibitors. So two main points of distinction.
First, whereas the NE inhibitors attempt to inhibit the activity of active neutrophil elastase once it's already been released from the neutrophil at the site of inflammation, one thousand and seven prevents the neutrophil elastase from ever becoming active. So we think it's acting more upstream in the process. And number two, of course, whereas any inhibitors address only one of these three NSPs, 1,007 would address all three. So for those reasons, we think there's good scientific rationale to believe that DPP1 inhibition may be preferable to any inhibition. So now that I've shown you how 1,007 inhibits the activation of the NSPs, I want to say a few words about what NSPs are.
As I mentioned, the NSPs are formed within the neutrophil while it matures in the bone marrow. And once formed, they remain stored within the neutrophil. While NSPs do have a direct antimicrobial role, they also have potentially damaging activities. For instance, NSPs are a component of the so called neutrophil extracellular traps or NETs. NETs are released by activated or dying neutrophils and consist of DNA and granule proteins, And there is emerging evidence to suggest that NETs play a role in various autoimmune and inflammatory diseases, including bronchiectasis.
In addition, as outlined in my next slide, NSPs have a number of activities that contribute to host damage, inflammation and other disease mechanisms. This slide summarizes various putative damaging effects of NSPs, which have potential relevance in non CFBE. I won't go through them individually, but my main point here is this. When we talk about NSPs in general, and particularly when we talk about neutrophil elastase, we most commonly think about their role in tissue degradation. So for instance, in the disease alpha-one antitrypsin deficiency, the emphysematous destruction of the lung is attributed to the enzymatic activity of neutrophil elastase.
So when I first heard about this opportunity, my first thought was, okay, tissue destruction is a component of non CFBE, and NSPs probably have a role there, so that makes sense. But I was also aware that the destructive airway changes progress slowly, meaning that it might be challenging to capture the benefit of a drug on that particular aspect of the disease. But as I read more and more about the various activities of NSPs, I realized potentially play a role in many aspects of the pathophysiology of non CFBE beyond just the tissue destruction. They may play a role in the mucus production and accumulation and in the inflammation that are also part of the disease. So when I was at FDA and we'd be evaluating a new compound, a new IND for a compound that had a novel mechanism of action, one of our first thoughts was always what could go wrong.
So starting from the premise that God made this enzyme or this receptor for a reason, and if we start inhibiting it or blocking it, what bad could happen. And for the most part, there wasn't a good way to know. You just hypothesized based upon your understanding of the mechanism of action and the pathophysiology and maybe from some tox findings. So one thing that was really important to me as I assessed this opportunity during our diligence process was this disease here called papillomavirus syndrome. It's extremely rare and I never heard of it at the time, but it turns out it's a very nice model of DPP1 inhibition.
Papillomavirus is a genetic disease in which patients have inactivating mutations of the DPP1 gene. So this is an accident of nature, and it's a circumstance that would mirror the pharmacologic effects of 01/2007. It's not often that you have such a thing. So we look to this disease for insight into the potential adverse effects that might result from excessive inhibition of DPP1. As it turns out, the primary clinical manifestations of papain la feve are dermatologic, so called palmar plantar keratosis and periodontal.
And there's no indication of serious systemic immunodeficiency, which one might worry about. In addition, the clinical manifestations of papain la feve seem to appear only when DPP1 activity is minimal or entirely absent. But with the therapeutic use of 1,007, we'll be aiming for reduction in the activity, but we won't be aiming for complete inhibition of the enzyme. Another thing that we found very helpful and informative during the diligence process was the Phase I study that AZ had already conducted. This was a single and multiple ascending dose study in healthy volunteers.
During the multiple dose portion of the study, the drug administered once daily over twenty one or twenty eight days. The study demonstrated that the drug had a well was well tolerated and had a PK profile that supports once daily dosing. Perhaps most importantly, though, to me was that the study established proof of activity with a clear dose dependent inhibition of neutrophil elastase activity. So we believe that these findings support advancement of the compound into Phase II. So we think we have a biologically active, orally bioavailable small molecule compound that has an MOA that suggests it might be impactful in circumstances where there's neutrophil driven inflammation.
So where do we begin? What's the first indication to pursue? Well, as you've heard, we've chosen to initially go after non CFBE. And there's a number of reasons for that decision. First of all, as you've heard, the disease fits very nicely within our firm's wheelhouse.
It's a rare, serious pulmonary condition with high unmet medical need. And as Doctor. Winthrop also mentioned, neutrophilic inflammation plays prominent role in the so called vicious cycle or vicious circumstance situation that's characteristic of the pathophysiology of BE. In addition, also previously mentioned, there's quite a bit of overlap between non CFBE and our firm's lead indication, NTM. Bronchiectasis is a key feature of NTM lung disease, and many patients with underlying bronchiectasis may develop NTM.
So all the many of the experts and clinicians with an interest in NTM also care for patients with non CFBE. In addition to the overall attractiveness and fit of the disease itself, there was also some promising data from a couple of studies that AstraZeneca had conducted with a related compound, AZD-nine thousand six hundred sixty eight. Nine thousand six hundred sixty eight is a neutrophil elastase inhibitor. Earlier, I mentioned the mechanistic relationship between NE inhibitors and our compound. And as you'll recall, we believe there's a scientific basis to expect that a DPP1 inhibitor may prove to have greater biological activity than an NE inhibitor.
So we looked at the results of these two studies with interest. One study was a large Phase two study conducted in patients with COPD. That study failed to establish a benefit of nine thousand six hundred sixty eight in the overall population. However, in a post hoc subgroup analysis of patients with a bronchitic phenotype, they saw a potential signal on lung function. The bronchitic phenotype of COPD refers to a subset of COPD patients with chronic cough and purulent sputum production.
This is a clinical phenotype that's quite similar to that of bronchiectasis. The second study was a small four week signal searching study in patients with non CFBE, and that study showed signals on lung function and on inflammatory cytokines. So the findings of these two studies conducted with an NE inhibitor give us confidence that non CFBE is a good target for one thousand and seven. Finally, I'd like to point out a very recent publication written by one of our expert advisers, Doctor. James Chalmers, whose work was quoted by Doctor.
Winthrop a moment ago, which lends further support for the notion that NSPs may be harmful in bronchiectasis. This was a very interesting and relevant paper I recommended about two weeks ago. It was at the World Bronchiectasis Conference in Milan, and the data from this paper made it into several of the presentations during that conference. In this study, elastase activity in the sputum was shown to correlate with both disease severity and with longitudinal outcomes in patients with non CFBE. So this paper further supports the promise of INS1007 in this disease.
Perhaps by decreasing the activity of NSPs in the sputum, we may be able to favorably impact the disease process. So we're very excited about 01/2007, and we're moving forward with a Phase II trial in non CFBE. You'll hear more about that from Doctor. Streck in a moment. But based on the mechanism of action, we believe that one thousand and seven may have a potential role in various other indications.
Here's a partial list of diseases that we think could be potential targets based on the role of the neutrophil. The last one on the list is a rare vasculitis that's particularly intriguing, at least from a scientific perspective, because in addition to an element of neutrophilic inflammation, it happens to be associated with autoantibodies to one of the NSPs, proteinase three. Back when I was practicing pulmonary medicine, we knew the antibodies were markers of a disease, but we didn't know whether they were part of actual pathophysiology. More recently, there is evidence that they are indeed part of the disease process, raising the possibility that decreasing the expression of proteinase three might be
beneficial. We've got some
work to do to investigate the promise of 1,007 in these indications, but we're hopeful that some of them may turn out to be promising. Now I'd like to introduce Doctor. Paul Streck, who recently joined Insmed as our Chief Medical Officer. Paul came to us with a rich background in the pharmaceutical industry, including senior roles at GSK, Shire and Amgen. I'm very pleased to have Paul on board at Insmed, and now he's going to give you some color on our upcoming Phase II study of INS1007 in non CFBE.
Well, you, Gene, and good morning. I hope you're having gaining a sense of why and how things are evolving at Insmed. And even in the short period of time that I've been in the organization, a number of critical milestones have been hit, certainly more of what you'll hear about now. I joined the organization about six weeks ago. And when I think about why did I join it, I think it's a theme that you've heard here throughout various speakers.
I think it stems from the exceptional talent, the passion and humility that starts with the management team and really extends through the entire organization. Next, hopefully, you've also seen a portfolio that's really starting to take form and take off in to help patients with rare and orphan pulmonary disease. So in my time with you, I'd like to do a couple of things. Number one, tell you briefly about myself, help you to appreciate the opportunity of 1007 and also give you a sense of how we will approach drug development in rare diseases. So I've been committed to patient care and R and D for the past twenty five years.
I've had the good fortune of previously working Jefferson Health System in Philadelphia, Amgen, Shire and most recently GSK. My responsibilities have extended from Phase I through Phase IV clinical development within the medical affairs as well as commercial marketing. I've been involved with multiple launches and have had responsibilities for global development registration of products in multiple therapeutic areas. So I'm excited to introduce to you the WILLOW study utilizing 1,007. Naming a trial always brings a lot of interest and discussion in terms of where did it come from, is it some sort of an acronym.
Well, WILLOW study comes from an arbor theme that we have at INSMED, which really stems from a quote from FDR. That quote being, Forests are the lungs of our land, purifying the air and giving fresh strength to our people. Certainly, this quote aligns with our commitment to patients with rare and ordinary pulmonary diseases. So when we're looking at a Phase II trial, there's clearly challenges associated with developing a rare a program in rare and orphan diseases. Number one, there's limited knowledge about the disease that you actually have.
And secondly, well, is the mechanism of action appropriate? So I can say within the rare and orphan space, we will consistently strive to conduct clinical trials to understand both the disease process as well as the mechanism of action. Certainly, we have primary endpoints, but we'll really utilize secondary endpoints and other analyses to understand where there's applicability in a disease that's extremely challenging to manage and also subsequently what does good look like in the long term for these patients. Let's go back. So we had a very good discussion with FDA related to our pre IND meeting and subsequently have filed our IND last Friday, July 14, and anticipate that it will be effective in thirty days.
It is a program which will enroll globally, and we will seek discussions with other health authority agencies to optimize our development plan. All right. So let's talk a little bit about the design. So in developing the design of the WILLOW trial, we really took a deep dive certainly into the pathophysiology, epidemiology and design of other recent trials. And as Doctor.
Winthrop indicated, kind of a mixed bag in terms of is this the appropriate place to break the vicious cycle. We believe that based on Gene's discussion that with a first in class mechanism of action, we really do have a good opportunity to understand how this is going to interrupt the disease and the vicious cycle. So we will evaluate two doses of the medication, ten mg and twenty five mg mg versus placebo, and we'll do this over thirty two weeks. Now that includes four weeks of screening and four weeks of follow-up at the end. So they'll actually be receiving on drug twenty four weeks of the trial.
We do believe that this is going to provide us with the necessary evidence around the dose response, efficacy and safety. We'll also stratify for background treatment presence of Pseudomonas because, again, the subtypes associated with this disease are variable. So we want to ensure that we're clear in terms of where there is activity with the drug. We're comfortable with thirty two weeks recognizing first and foremost, this is a Phase II program and the analysis contains elements critical to developing the level of insight necessary for late phase development. We have taken into consideration the need to have an adequate number of exacerbations.
So we've done a couple of things. Number one, we've conservatively estimated the rate of exacerbation. And secondly, we've built in a blinded evaluation to enable us to adjust the sample size as appropriate. The current tox data we have limits our exposure to thirty two weeks. However, we are planning for a new chronic tox study to enable us dosing for longer periods.
The primary endpoint will be to evaluate the time to first exacerbation. But clearly, there are other things that need to be taken into consideration in this Phase II program, specifically what's the rate, what do the serum protease levels look like, how are patients performing from a clinical perspective in terms of their FEV1s and ultimately from an outcomes based perspective, how are the patients feeling because, again, there isn't this is still a rare and orphan disease. So the amount of work that's been done on it really has not disclosed the amount that we really need to understand both the disease as well as if 1,007 has utility in that. We will also certainly be looking at the usual safety and pharmacokinetics. So I feel like when we finish our Phase II program, we'll have a really good sense of what one thousand and seven can do, who the right patient population is and move forward in a very responsible way to hopefully find solutions for patients with a very challenging disease.
So on the operational side of things, we will enroll an estimated two forty patients, so that's 80 patients per arm in 125 sites, so that will come from North America, Europe, Australia as well as SmallDOT and PAC RIM. Now there is planned discussions with the Japanese PMDA. We'll see how that goes because as we had alluded to, Japan is clearly an area that needs drugs in the pulmonary space.
So hopefully, I've given you
a sense of why 1007 represents a real opportunity in rare and pulmonary diseases. Consideration of where 1007 may go in terms of life cycle management. Again, I appreciate the opportunity to make the introduction. I look forward to continuing to update you as the trial progresses. And subsequently, I now have the great pleasure of introducing my new colleague, Paolo Tombasi, Chief Financial Officer.
Paolo joined the organization about a week before I did, so we've been coming up the learning curve together. And Paulo, across the entire management team, it's just been a real pleasure to integrate into the organization. So again, thank you very much. And Paulo?
Thank you, Paul, and good morning, everyone. It's a great pleasure for me to be here. My name is Paolo Tombezi. I'm the Chief Financial Officer at Insmed, and I'm going to spend the next few minutes to give you a quick update on the financials, but also and foremost to introduce myself since I recently joined Insmed. And this is the first opportunity that I have to talk to all of you.
I'm sure that you already guessed from my accent where I'm from, and you're right, I'm from Italy. I was born and raised in Rome, but then I moved quite a lot around the world. I have more than twenty years of experience in the pharma biotech industry, almost evenly split between Bristol Myers Squibb and Novartis before moving to Insmed. I work with those companies in several countries and regional roles in Europe, but then also in The U. S.
And Japan. And I think it's quite clear now that U. S. And Japan and lately Europe will be the key regions where easement is going to build its future. Working with companies like Bristol and Novartis highly focused on innovation R and D, I've also had the opportunity of supporting many launches.
In the last decade, when I assume senior finance roles, we launched more than one product per year, and many of them became blockbusters. Just to name a few, when I was the Senior Finance Director for Europe and BMS, we launched Abilify. During my tenure as a CFO, Regional Europe Oncology Novartis, we launched Tasigna and Afinitor. I spent six years in Japan in the moment of a high acceleration of pre NDA approvals, and we launched many products, including the COPD family with the LABA, LAMA and its combination commercialized as Cebri, Ombrez and Ultimran. After Japan, Novartis asked me to move here to be the CFO for the Novartis Corporation in The U.
S. To be part of the team to launch Cosentyx and Entresto that was supposed to be blockbuster for the company. So this combination of international experience, especially in U. S. And Japan, commercial organization globally and multiple launches.
It's clearly a great fit for me with Instant in this moment, which we have an inflection point, a tremendous growth. When I decided to move first, I met all the senior team. As you can see, it's a great team with a background, very experienced and high caliber. And I can tell you that in the first seven, eight weeks that I worked, I see the same level of talent and caliber throughout all the organization. It's really a lot of people, very passionate, engaged with the mission and behaviors and values that Will mentioned at the beginning.
I've also experienced all of these launches, and I can see here what I've learned to be successful is in place, the go to market, the in-depth patient understanding and also to work in advance in the best in class patient service, anticipating discussion with the payers and the market access is really creating the set for success. In terms of the financial update, as we already publicly disclosed at the end of Q1, we have enough cash and resources to bring the company to 2018. We will go into more details about the financials when we will disclose the Q2 results at the August. So I believe that you appreciate that at the moment, I cannot go to any further details pending the disclosing time in a couple of weeks. In any case, we have, of course, high focus on what is, at the moment, needed to complete the CONVERSE study, and we're ready to wait for the results in September.
But at the same time, I was already working for the investing for the future. You saw about eventual additional indication for ALICE, but also the INS1007. And we are also preparing all the fundamental activities for the successful launch. And for the future planning, of course, we are planning to expand the organization globally. So this will allow us to also make a thorough decision on where to maybe establish organization, scale up our manufacturing capacity.
And we will maximize, of course, synergies but also minimizing cost, optimizing tax rate for the future profitability. So it's, for me, a great pleasure to be here, and I joined a great team. And I would like also to thank you all for all the support so far to Insmed. We will have many opportunities to interact in the future and are really looking forward to working with all of you. With that, I leave to our President and CEO, Will Lewis, for the closing remarks.
Thank you.
Thank you, Paolo. It's an incredibly exciting time for us to be at this point in Insmed's history. We greatly appreciate the role that you have played as investors in the life of this company. More than anything, I hope you have seen today the depth and breadth of talent that we have assembled that will allow us to fulfill our ambitions. I also hope you take away some sense of the commitment that surrounds all of us as we tackle the enormous challenge of getting a first in disease drug potentially approved for this difficult condition.
We have assembled a cadre of high achievers who will drive towards success without the slightest managerial direction. They do so because it is in their nature. This approach is responsive to the inquiry about what we will do and how we will do it, but the most important driver in our behavior that moves our collective actions is the why we do things. Our decision to work in this industry comes from the fact that we get to help people confront potentially life threatening diseases. Along the way, we find genuine inspiration from the occasional anecdote we hear from patients that suggest that our drug may potentially be able to help them if we can establish that it is safe and effective.
And I want to share one such quote. It's an unsolicited posting from a recent patient support group website, and it reads, I have NTM and have been in Insmed's drug study for eight months. I'm interested in helping others in my area who have NTM. I would be willing to start a support group. I am improving every day with my current drug regimen and would not be alive if it weren't for Insmed.
Now it's important to remember that our drug has not yet been proven safe and effective. It's an investigational Phase III drug, and we all understand this. But when we hear this kind of testimonial, and we need to be aware, this patient's experience may not be matched by others. It's their personal view. Indeed, we may not be able to establish safety and efficacy for our drug.
Nonetheless, drug development, as we know, is a long road. It's a difficult journey. And whatever challenges come along, these sentiments expressed by this patient motivate us to continue to advance the compound with the hope that we can someday validate this perspective. This is what motivates us, and it is why we are excited to share this detailed update with you today. With that, let me invite my colleagues back up on stage and open the floor to your questions.
Ritu. We already have sorry, Adam in
the back. Sorry. Adam Wahl, Stifel.
Yes, thanks.
And if
I can just say, if you can introduce yourself to the audience, especially for the benefit of those on the line.
Thanks. Adam Walsh, Stifel. First of all, thanks for hosting the day. Really informative. I appreciate it.
My first question is for Doctor. Winthrop. Regarding when we looked back at the Phase II data and applied the Phase III culture conversion criteria, it looked as though the standard of care arm had about a three point seven percent culture conversion rate. Do you think this is a good proxy to expect with the in the CONVERT study for the standard of care arm? That's my first question.
Thank you.
Yes. Have no idea if all that's right, but I'll trust you. I could be right. I'd have to go back and look at the data. But I think our general sense is for most people who are refractory that the chance they're going to culture convert is very, very low.
And we usually say five percent to ten percent. So I would use that probably as the ball ballpark, but it might be three percent. I mean, generally tell patients that if you've made it this long, have a culture converted, you probably aren't going to unless we do something totally different or get lucky, but it's really low.
Great. And then, Will, in talking to key opinion leaders, some have suggested that the FDA had really wanted to see a clinical outcome measure. And I know you selected six minute walk distance based on the results from the earlier Phase II trials. Can you help characterize your discussions with the FDA about the importance of that endpoint and whether or not you think it matters for initial
approval? Appreciate that question. As has been discussed during today's presentation, and you've heard me say in the past, the primary endpoint of this study is really the crux of the whole matter. Under a subpart H analysis, clearly, hitting that primary endpoint, which is a surrogate for durable conversion, is really the most important thing. And that's what we're, I guess, the most hopeful for.
The secondary endpoints we have actually, I'll ask Gina to comment on how we brought these forward because as you may recall, Phase II was very much a pioneering study. No one had done any clinical development in this disease state for literally decades,
and
there was not a good understanding. And as she comments on this, I would just reflect that I think we are not alone in our evolution of understanding this disease. I think the FDA has come along that journey as well. The patient focused Drug Development Day and their subsequent commentary, I think, is informative about how they have come to understand the disease and the challenges of developing drugs for it. And I'm pleased that their sentiment continues to be an eagerness to try and find drugs that can address it.
But Gina, maybe you can talk about the specifics of the secondary endpoints and why we brought those forward.
Yes. So in developing a drug in the different phases, of course, you have to try and use the assumptions that you know are factual based on a prior study. And when we did see the six minute walk test, the results in the Phase II study, This was something that was a tertiary endpoint, but something that was a clear signal in that particular study. And I think we do have to bring that into the Phase III study as well as introducing or putting some of the like the St. George's Respiratory Questionnaire and those patient outcome measures as well.
But remember, none of these measures are validated for NTM lung disease and the treatment outcome. And this really goes back to the fact that this is the first study really of its kind. And even the FDA, you hear them speak as the representatives from the division, they still don't have a they don't come out and say, Well, this is the clear patient reported outcome we want to see. And also bear in mind that this is an open label study that we already have discussed with the FDA. And the primary endpoint is a microbiological endpoint that doesn't get impacted by an open label study.
It's either going to be cultured or it's not going to be cultured in the sputum of these patients. So I think going back to what Will said, we really do need to look at the primary endpoint, which is a surrogate for the final endpoint or the confirmatory endpoint of durability of a culture conversion in these patients.
And I guess I would just add to that. I think we found it encouraging that there appears to be a consensus in the treatment community that this is the right endpoint to be examining. And as well as we've engaged with payers around the world, they, too, share this perspective that this is the right endpoint to be examining.
I think we're going to
learn a lot from the Phase III study. We'll look at Six Minute Walk. We'll look at St. George's. We'll look at TYME-two culture conversion.
No doubt, we'll unearth some new learnings there. They may all go our way or they may not. I think the point we're simply trying to highlight is that for purposes of how we're going to feel when we unblind the study, if we hit that primary endpoint, we intend to file.
First question for Doctor. Winthrop. Can you talk a little bit about where this would fit in the paradigm treatment paradigm per your Slide 21? Do you think that ALICE would fit in place of one of the first three? Would it be the fourth?
And is there I mean, this is refractory disease that we're talking about for the trial. Is there a population of high risk first line MAC patients where you would want to use it even before a label was flushed out for first line? I have a follow-up for Will.
It's a lot of questions. But I think you have to remember just like any drug when it first comes out, it's going to be used what it's labeled for and it should be labeled for how it's studied. So I mean, it comes out, it's going to be, I would think largely employed in the refractory disease population. But I do think I highlighted those other areas. And then I think Jean did or someone else had the triangle up there in the pyramid that you can imagine this being useful for us.
So I do encourage the company and others to support further studies to examine the efficacy and safety of the compound in those settings. But I mean to answer your several questions in one answer is that I could see using a drug like this right away patients, in fact, most patients. And so there are high risk patients in terms of toxicities, to answer your question, that they have they already have problems or you know they're going to have a difficult time or inability to tolerate one of those first three drugs we use. And so we're looking for a replacement right away in a whole number of people. And again, I'm not saying you could advocate using this drug in those people yet because it has been studied there.
But I mean, I think ultimately, there's a potential for using it right off the bat in many, many patients. In fact, the vast majority of patients. There's some people that would prefer an oral therapy. There's other reasons I'm sorry, an inhaled therapy. There's other reasons to think about that.
I mean the drug goes right to where theoretically you want it to work. It will not have the systemic side effects that other oral therapies have. A lot of these folks are older and again these drugs interact with their other meds or they get diarrhea or they don't want to eat, they get all sorts of problems from systemic meds that inhalation med might be optimal for them or more optimal. So I think ultimately I hope that the drug if it's shown to be effective that it will be studied in these other situations. But I think you can make a case for it being used if it works very early on in therapy.
And then even ultimately long term, it's kind of a preventive. So I think there's a lot to be done. And I just want to
clarify, those are decisions that physicians will make. We will not be pursuing any of those indications unless and until we've conducted the appropriate clinical trials.
Will, my follow-up question is how you're thinking about pricing right now given the pharmacoeconomic data that you threw up there today on the screen. What is going to factor into your pricing decision? And how are you going to structure pricing? Is it sort of a monthly on a monthly basis or treatment course basis?
Yes. I appreciate that question. I'm actually going to turn it over to Roger and just observe that we actually have some real time data out of Europe that gives us some perspective.
Yes. Thanks, Will. So I think our approach on pricing is really to take a value driven approach to this. And probably you start with the I think it was Will who started out with the ten plus years of work and the $800,000,000 that it's taken to get here as our initial basis. And then, of course, the data that we get back from the CONVERT trial will be very informative as we start to think about what the value of this product is.
You layer on top the significant unmet need, the fact that there's no approved product for NTM, there's no product with an indication. And we talked about the significant costs and think about it in context with other serious rare pulmonary diseases. So I think that when we talk to payers, they are expecting a premium price to come across associated with this product. Will mentioned Europe and the European price. And one of the things that we're learning from our European experience is the value of the product, at least through the physicians and the authorities in Europe.
And we recently secured a reimbursement price for the ATU program in France that was €80,000 which I think is reflective of at least the value they see initially. And that typically acts as a ceiling for the price in Europe. As far as whether it's going to be a monthly or a yearly or a course of therapy, I think we'll price it per vial is our initial thought, depending on the duration of therapy that's required for the patient.
Thanks, and thanks for this really great deep dive. My name is Lisa Baeko from JMP Securities. I'm really sort of intrigued with the opportunity in Japan. It seems very substantial. Can you maybe talk about any preliminary discussions you've had with the Japanese FDA and what other work may be required or not before you're ready to submit there and maybe a little update on any timing plans there.
Sure. So as was mentioned by somebody during today's presentation, I can't recall whom went into it, but we did have a dialogue with the PMDA prior to initiating this study with Japanese subjects. And the purpose of that dialogue was to clarify exactly what would be required for registration and approval. And while that discussion is obviously preliminary, it did frame out the need for, as is typically the case, a separate PK study, which we were able, because we approached them early, to embed within this study. They set a minimum number of patients we had to have in that study and the specifics that it would need to address.
I'm happy to say that we have that study built into this one. So we're in a strong position to return to PMDA based on the data and have a dialogue about what's the appropriate path from here to registration and approval. Our hope would be that this would be adequate, and it certainly was our initial impression, but that's something I think we would need to confirm. And a big factor in that analysis will clearly be the content of the results from the study. I don't know, Roger, if you want to add anything to our approach to Japan.
As I mentioned, we're planning on putting a small presence in Japan assuming we get a positive outcome next year to really understand what kind of approach we need to take there to more fully understand that opportunity.
And then I just wanted to ask about kind of your goal for the initial indication on the label. I understand the focus in the refractory population. But then drilling down further, do you expect it to be just focused on MAC or maybe species outside of MAC? And then also, do you think CF patients would possibly be treated? Or would it specifically specify non CF?
Because I know that's a big potential opportunity as well. So curious about that.
Yes. I think, again, the data will dictate what direction the dialogue will go. But our assumption, and certainly, the assumption that underlies all of the numbers we talked about today, is that we will be looking at a label that identically matches the entry criteria for our Phase III study, which is non CF MAC patients.
Okay. And then just one more question for me, actually for Doctor. Winthrop. We've seen the sort of side effect profile and all that kind of stuff. I'm really glad that the discontinuation rates seem to be lower in the Phase III.
Can you maybe just give us kind of a real world perspective on how well tolerated this drug is? You talked about these patients being generally older, perhaps having some other comorbidities specific to the lung. So this is an inhaled therapy. How tolerable really is it in kind of real life and how motivated are patients to stay on?
Sure. And I'll also say, too, I'm glad you brought CF up because we didn't talk about CF. But NTM and CF is a big deal and it's increasing and we do need therapies there. So I would encourage all of you to help there as well. Tolerability, I don't know the data from the current trial, of course, of us do.
I think the last trial that was published, I think Gina showed it. My $02 would be anecdotally, I don't it doesn't seem any less or more tolerable than any of the other antibiotics that we're using in these people right now. So think the word on the street with what we have now is that it's hard to tolerate for a lot of people. So I don't see this being any worse than that. If anything, it might be an improvement for certain people.
Like I said, I think some of it comes down to preference, what people prefer to do. And most people don't like to have IVs and a lot of people don't like to have systemic antibiotics. So I do think the inhalational route is something preferable prior to some people more than others. In terms of the side effect profile, I mean, like with any medicine, there's ways to make it more tolerable. And I think it's it'll be good to educate your clinicians and that's probably what you do in the study, right?
Like how do you make drugs more tolerable and there are certain things you can do. And like with rifampin, the pharmacist says, taking on an empty stomach on a bottle, well, I can tell you never do that because you ain't going to like it if you do that. But so there's little things that you do with any drug that you help people improve their tolerability. So I don't really see anything different here than I do with the other drugs.
And just a historical footnote, as many of you are aware, we actually have studied this drug in cystic fibrosis and hit our primary endpoint in a Phase III study across Europe for the treatment of cystic fibrosis patients who have pseudomonas infections. So one of the things that gives us a lot of confidence about the path we've followed is that this drug has been explored in a number of diseased pulmonary settings from non CF bronchiectasis to cystic fibrosis and now, of course, our area of greatest focus, NTM.
Joe Schwartz at Leerink Partners. Gina, you mentioned how heterogeneous this population
might be when talking about
the Phase II data. And a lot of one thing that a lot of people detect there is some randomization imbalances. And then you also highlighted that amikacin resistant patients are being excluded in this trial. That was only like eight patients in the Phase II, I think. But could you talk a little bit about whether you saw that there were any of the separation in terms of the conversion rate was driven by the difference in bacterial load or macrolide resistance that the patients had because those were two other areas that it looked like the randomization was not that well balanced in Phase II.
So starting off with the amikacin resistance, I mean, the Phase II study was a small study to start with. And so you try and do the best you can when you go into a Phase III study. And certainly, if we see when we saw the MICs greater than 64 and we saw that in that short period of time, those patients didn't have a negative culture but neither did others. But we just decided to exclude those patients at baseline because we do get one shot at the Phase III, and we didn't want to have like an enormous number of patients to sort of cover for that. In terms of macrolide resistance, I think that's still an unknown, and it was an unknown when we were putting the Phase III study together because we're not actually delivering a macrolide to these patients.
And so it's really hard to sort of connect the dots and make assumptions. So we are allowing patients to come in. But remember, patients are coming in on guideline based therapy. And the guidelines, if a patient is resistant to a macrolide, then those medications that are coming on that they've been on for many, many years may already have been adjusted to account for that. And then the randomization process accounts for that again.
And so we really didn't see any reason to exclude those patients. And then in terms of the bacterial load, now you're referring to a semi quantitative scale that we're not using in the current study because we it's very difficult to sometimes interpret scales like that, that are not validated. And whether or not somebody has a step higher than the other, it's a very individual thing in terms of how that presents as actual lung disease as well. So the current study does not utilize that scale for that reason.
But did you notice that patients with who were macrolide resistant converted to any greater or lesser degree more likely? And the same thing with the bacterial load. And are you stratifying according to either of those factors?
No, we're not stratifying for those factors. Numbers are small, and we don't actually look at bacterial load. We just look at whether patients are positive or negative.
Okay. And one of the challenges, obviously, with the bacterial load measurement, the SQS scale, is the variability of sputum inherently in the sampling creates some challenges. Again, when I first arrived at the company, we had a call with both FDA and EMA prior to even unblinding the results of the study. And for these reasons and others, to my great discomfort at the time, they expressed total disdain for that primary endpoint in the Phase II study and reminded me that they had guided the company to look at culture conversion as the appropriate measure. So while I think it is interesting, and we certainly spent a lot of time looking at our Phase II data, we draw attention to the culture conversion analysis as the most probative for whether the drug is having true impact on the underlying disease.
Great. Can I just ask one commercial question? You bet. So I thought it was really thoughtful how you were guiding the patients to suspect NTM when they have fatigue, shortness of breath and coughing. How do you encourage people to then take that information and seek a definitive diagnosis based on what the guidelines suggest, which is a well, maybe you
can talk about that.
I think it's sputum culture as well as imaging and maybe something else. How do you guide people to then rule out other things or rule in NTM? Sure. I'll just ask Roger if
he wants to address that.
Yes, sure. Thank you for the question. So I just want to refresh everybody's memory that we first started out by launching a disease education and awareness for physicians. So we know that there's a gap in that index of suspicion, so we want to raise that for physicians. So if a patient shows up, that they start to think about NTM.
As part of the patient disease awareness, and Colleen mentioned the website that we have set up, There is a discussion guide that you can download for that the patients could take to their physician to initiate that discussion. And we know that after getting that information, a lot of times, the patients will feel much more comfortable in having that discussion with the physician and talking about whether or not this is something that they should be concerned about and whether they should explore a definitive diagnosis there. Again, ultimately, that's going to be the physician's decision, but it is encouraging the patient to talk about the symptoms with their physician.
Gina, do want to add something?
I think, Joe, I don't know the way you asked the question. I'm thinking that what the campaign is trying to do is raise the index of suspicion. It's not a protocol for a patient going to their physician and saying, need a CT scan or I need a sputum. That will ultimately be the physician's decision. It just introduces just have you thought about this because we do know that a lot of physicians do not think about this.
And in terms of sputum, at least, you have to actually actively send the sputum for mycobacterial culture. You can't just send it to the lab and say, Culture, because then they'll just do a bacterial culture.
Adam? Thanks, Will. Adam Walsh, Stifel. Will, I get this question from clients all the time. And I understand that your guidance is for data in September, plus or minus a month.
But I'm curious, with the last subject now having exited month six, whether you can provide any more granularity beyond the three month time window that is current guidance?
So I'm smiling up here because we had this active debate about whether to announce this little feature that the last patient had cleared because we knew it would immediately generate the follow-up question, which is now you should be able to give us greater clarity. At this stage, we don't feel like we can do that. We obviously have our quarterly call coming up at the August. We may be able to give greater insight on that call. The reason for this, again, just to reiterate, is last patient has had their last visit.
Now the process of culturing begins. As you
know, that can take up
to eight weeks. And then once that's done, the data is collected. It gets entered into the database. And then the logistics of ensuring the quality control of the database has been done have been done to their completion. Then you lock the database, you examine the initial results across a whole variety of test metrics.
So these processes I'm describing are common to every study that's conducted with an eye toward quality. And they can take days, they can take weeks, it just depends. So we want to buy ourselves a little flexibility so people aren't wondering what's going on. We'll be as specific as we can be as soon as we know more.
Liav Abraham from Citi. Just a quick question on your thoughts on the durability of culture conversion. So assuming you the trial is successful and you get approval under Subpart H, Maybe talk a little bit about any basis or assumptions for the probability that you would be able to show the durability of this of conversion and any thoughts around that to get final approval?
Sure. Appreciate the question. When it comes to durability, I think one thing that has emerged from Ardala with various regulatory agencies is that the EMA and FDA are aligned on the three months off drug as the measure for appropriate durability, the appropriate durability test. Our guidance right now on how we think about what is a good number there really, again, comes from the Phase II study because it's the only available data. And I'll ask Gina if you want to comment on what we saw in Phase II.
Again, small sample, post hoc analysis but still, I think, informative.
So the Phase II study, obviously, a small sample, and we treated patients for up to one hundred and sixty eight days for those that started on ALICE at the beginning of the double blind phase. What we saw were that patients that did achieve conversion, and I think most of you are familiar with the actual graph that we have in the manuscript for the Phase II study. What we did see was and this is all post hoc, and we had a twelve month follow-up period, not a three month follow-up period. But regardless, the patients that of the patients that were non CF, MAC and converters at the end of the treatment phase and the twenty eight day follow-up, when we look at those patients twelve months out, they the majority of those patients actually remained negative. And the majority of those patients were actually off all treatments for months prior to that twelve month follow-up.
So this is really what gave us the confidence that we should be able to see durability after successful treatment. Now remember, the Phase III study is patients who are converters continue on for a full twelve months of treatment with whatever their treatment armies had achieved conversion before stopping all drugs and then having that three month culture follow-up.
So if I can just add, I think that means we're looking at a much more robust treatment phase in Phase III and a shorter window to examine relative to what we had in Phase II. To be specific in response to your question, we do not have a pre agreed threshold that we have to clear in our dialogue with FDA. It's simply the measure that they will be looking at, which is three months off all drug, what is the durability measure that we observe.
Ritu?
Thank you. Ritu from Cowen again. A very specific question for Gina and Paul. Based on your powering, what is the minimum delta in the primary endpoint that will still give you statistical significance between placebo and treated? And then I have a quick follow-up for Doctor.
Winthrop.
Don't know that we I'm going
to dive in because I don't
know that we've actually run a reverse sensitivity or statistical analysis to determine what the minimum would be. It's possible that we could end up with a study that achieves statistical significance with less than 15% threshold. We've contemplated that for a long time, but we just won't know. And I think we'll be in a better position to interpret that once we've unblinded the study. I will reiterate that even if we do see less than 15%, if we hit statistical significance, while the meaning of that is a subject of discussion, it certainly would be something we would move forward with because, again, as we've heard repeatedly, not just from folks at Insmed but also from thought leaders in the space, these patients really have nothing else.
And the ability to convert any of them and then establish that, that conversion was actually durable, we think, is a material accomplishment that the FDA will recognize.
So can I flip that to Doctor? Winthrop actually? Like what would be the minimal difference that you would consider important? Like what if placebo was like 3% and active was 9%. What would those sort of numbers tell you versus the 5% versus 20% plan?
Well, I mean, obviously, on an individual basis, the answer is, geez, any conversions great for you. I mean, I think going back to Adam Walsh's question, I mean, I think we think the refractory group, it's unlikely they're ever going to convert. So I think even just a few percent sounds pretty good to me. So I think if you can get 10% or 15%, 20% of fuel to convert, that's news, and particularly if you can make it durable. So I think the number is pretty small.
I don't know what the number is in the placebo other than or the observational wing. I mean, this has always been one of the challenges with powering these type of studies. You know this. FDA knows it. We all know it because there really haven't been studies before the last one to help us with these things.
I mean, what is the spontaneous conversion rate in a placebo wing or an observed wing? I mean, those are serious questions still that we don't really know firmly what the answer is. But I can tell you just our collective treatment experience and some of the observational data would suggest that people in the refractory who meet that case definition of refractory diseases, it's low and it's probably five percent or ten percent or even lower. So I think anything above that is fairly meaningful. It's a young science.
I mean, I think that's been talked about here. I mean, these endpoints, all these things we're talking about, I mean, this is all new. It's new for FDA. It's new for companies. It's new for us doing the clinical trials and scientifically.
And a lot of it is being extrapolated from CF and TB and all these other things where we kind of have something similar, but we don't and it's something different. So this all may be different in five years based on the data that you're generating from these trials. So I think this is as good as we know how to do right now, but some of these metrics might change.
And then you mentioned cavitary versus nodular disease in your presentation. Given the biomechanics of the lung, do you feel that the drug will work any different in patients with one type versus the other? And is that something that bears watching in the Phase III results?
Well, I think cavitary patients tend to be different than non so the percent of patients who have cavitary disease does differ between those two phenotypes. And it's more common in the people with emphysema and COPD. I mean, population based data, at least in Oregon, if that can generalize outside of Oregon, twenty percent to thirty percent of people have cavities, it's probably more like thirty thirty ish percent in the COPD group and more like twenty percent in the bronchial cat group. So it's not that different, but there is some differences. So I think when you're doing these studies, you do want to at least think about that in terms of your design or at least your analysis controlling for any differences.
Cavitary people do have higher disease burden, so they technically might take longer to convert their sputums. On the other hand, it depends on how big the cavity is. And some people with cavitary disease are much easier to convert because they don't have 10 focuses of foci of disease. Have just one like that lady I showed you in the picture. I cured her up for twelve months and she's been disease free for five years.
So that's a lot different than someone who's got a completely destroyed right middle lobe from bronchiectasis and like five other areas of bronchiectasis. So I think in the end, you do the best you can to kind of control for these things upfront and these potential differences, the difference between CF and non CF. I mean, that's why there's no CF people in this trial because they probably convert at different rates. It makes it real messy. So you do the best you can in terms of your entry criteria.
But again, at the end of the day, think some of this you'll answer some of these questions with your analysis.
Lisa?
Yes. Just a follow-up for Doctor. Winthrop. I'm curious how long you might keep a patient on ALICE in real life. I mean, are you going to is the metric culture conversion?
And if so, how often do you check for that? And how long might you wait it out? Or do you just keep them on as long as they you feel like they look like they're improving? So Or kind of what's the
I can tell you what we do now presently with the drugs we have. And so you can imagine extrapolating that to any inhaled therapy, including this one. I mean, we do go for eighteen to twenty four months. And I have to say myself and a number of colleagues have, can we go shorter? We tend to go maybe really twelve to eighteen months.
But then there's a lot of people you stop at that point, bounce back in the next year or two and they go back on therapy. And that could happen in three months, it could happen in six months. And so there are lot of people who end up on suppressive type therapies with maybe just two of the antibiotics or maybe it's an inhalational antibiotic plus one of the orals or something, something where you just your goal suppression. And actually, I mean, I know we're all talking about culture conversion, but there's a lot of people like, I don't care if they convert ever. I just care if I maintain their disease at the current level, like I stop progression and I make them feel better.
And that's really what the patients care about. So there's a lot of people that fit into that group where you're just giving them antibiotics as a suppressive to keep them feeling good and to keep the disease from progressing.
Very interesting. And then a follow-up for Gina. Just when you were talking about the durability in the Phase II, can you maybe speak to the crossover arm as well? Did you see the same thing in the patients who were initially on placebo that they took drug? Did the majority who converted, did they also have the same durability?
Yes. So when I talk about the converters in the study, I'm talking about them converting across both phases of the study. And the yes, those are in the patients where I say the majority had a negative culture. No. There were where we saw some patients that had that reverted to positive, the patients had really short duration or converted like on day 140.
There was a patient, if you look at that graph in the manuscript, they had like a broth positive, and that was like a relapse. But the ones that actually had a decent amount of treatment and became positive as a broth positive, those tended to have a new infection that you just they're sitting they're vulnerable to these infections. So they're very small numbers. I think if there's a takeaway at all, it means that you really have to treat these patients for a decent amount of time after they convert so that you can minimize the recurrence rates. And this is actually published in the literature that looks at relapse rates or recurrence rates.
And patients who have had less than six months of therapy or decent therapy according to the guidelines are more likely to have a true relapse. And patients who have had at least ten months of negative cultures where they've been treated appropriately, those patients have a much greater chance of having a new infection and much, much later on after they've stopped all their therapy.
Okay. I think that's where we're going to call it for questions. I want to thank you all for attending and invite everyone here to join us for lunch in the room right behind you. We're going to have a couple of company representatives at every table. So depending on what topic interests you, you can align yourself with who's at that particular table.
I'd also encourage you, as you walk out, just to take a look at some of the artwork that we've made reference to several times today. I think it really does speak to the heart of what it means to be an NTM patient. And finally, I want to thank Doctor. Kevin Winthrop for joining us today. I think his contribution was really quite significant.
So thank you.