All right. Fantastic. Okay. Excellent. Thank you, guys, for joining. Super excited to have Savara Management. I want to perhaps start with you, Matt, just to kick things off. For folks who are maybe not as familiar with the company, just remind us what you guys do, how late stage you are, and what's the indication, because I think some of those things may not be super obvious to people. Sure. So thanks, Umer, for the invitation to participate. We're thrilled to be here. So Savara Inc., is a single-asset orphan rare disease company focused squarely in the rare lung disease space. We have an inhaled biologic, Molbreevi, and we have positive Phase 3 data in a rare lung disease called autoimmune PAP, or autoimmune pulmonary alveolar proteinosis. So we'll refer to it as autoimmune PAP during the presentation. And BLA submission is actually this month, and then we will file MAAs in both Europe and the U.K. by the end of the first quarter. So we. So you're a commercial stage by healthcare conference 2026? Fingers crossed. We're very hopeful we will be. Fantastic. Fantastic. I want to sort of go through this in a fair amount of detail, but because the indication is maybe not the one investors often work on, it's an orphan indication, perhaps a question for you and your team, what exactly is the indication, and how is it treated right now, and somewhere in there, I want to hear the word power wash, so. Sure. You'll get all of it. I'm sure of it. So Brian, Dr. Robinson, do you want to take that? Yeah, sure. Happily. So autoimmune PAP, as was described, is, as Matt said, a rare pulmonary disease where patients present with shortness of breath, cough, and fatigue. And they typically have an abnormal CT scan that is not necessarily specific for autoimmune PAP, but is bad. And right now, patients are managed with a procedure called a whole lung lavage, which is a power washing of the lungs, as you've described. Have you ever done one or seen one? I have never done one. I've seen the setup of one. I've actually never seen one actually done. Can they shoot a fluid down, or how does it work? What they do is they put a double lumen endotracheal tube into the lungs, and they ventilate one lung, and they wash the other lung. That is anesthesia, I would imagine? Yeah. The patients are taken to the operating room. Thank you for mentioning that. They're taken to the operating room, and they're put under general anesthesia, and they have this endotracheal tube put down their throat. And as I said, they ventilate one lung, and they wash the other lung by infusing. They usually hang a bag of warm saline, and they infuse it into the lungs. And once it's infused into the lung, they bang on the chest to emulsify the surfactant. So it's like you're making salad dressing. They basically emulsify the fat or the surfactant that's in the lung. Got it. And then they drain it out using gravity. I got to believe insurance is not approving these left and right. So two things. One is that it's a procedure that's rarely done. It's not done at every institution in the country. In fact, there may be tens of them, maybe 50 or so people who do it in the United States. How many procedures a year? I don't know. We don't know that. We do know that, as I said, it's only done at a limited number of institutions. And if a patient is indicated to get one, they frequently have to drive many miles, hours, two hours, three hours to drive to an institution where they can have it done. Right. And Umer, I think it's important to note here, too, that we are talking about the most severe aPAP patients, autoimmune PAP patients. For whole procedure? Yes, for lung lavage. There is a whole long journey for most patients where they are symptomatic enough to get diagnosed, so maybe mild to moderate, right? And then the segment of severe, this is a rescue procedure. And what do they do along the way? There's not a lot that they do. Number one. Steroids wouldn't do much? Steroids actually do the opposite. They're not helpful at all. There's rituximab that at times is used off-label, not been shown to be effective. So a lot of nothing. Very importantly, time to diagnosis is unacceptably long right now. We have started to invest early with regard to no-cost dry blood spot antibody tests that we're offering right now that's being utilized to try to help speed that up. If you think about the way this disease, lung lavage will always be there as a rescue procedure. That's a good thing for patients in the event that they need it. What they need to do is address the pathophysiology of the disease. They need to turn the signal back on and get gas exchange functioning again, right? Get the alveolus to help the macrophage chew up and reduce surfactant burden. Right. May I ask just a quick follow-up on that question? What type of clinicians are seeing these patients? Or is it not even clear right now? It's quite clear. It's pulmonologists who are seeing them. It is pulmonologists. Yeah. Okay. Got it. And then who's doing the procedure? So that varies. There are regular pulmonologists who do the procedure. There are interventional pulmonologists who do them. Sometimes it's anesthesia. Sometimes it's cardiothoracic surgery. So it varies. But again, it's a limited number of people who actually do this. Okay. Got it. I guess that lends itself then to, is there a clear patient registry out there for this disease? There is a small registry that's being run out of Cincinnati Children's Hospital. And it's very limited. There are probably maybe 150 or so patients who are in this system. But is that biased towards the pediatric setting? No. It actually isn't. It's mostly adults who are in this system. It's mostly adults who are affected with autoimmune PAP. I guess I'm just curious, thought process from the team around what is the true prevalence pool? The EPI literature has a range of, from at the low end, about six per one million. In the current kind of high end, it is about 26 per one million, the Kitamura data from 2019. In the United States, we've done very robust U.S. claims database work, which I'll have Braden comment on. Yeah. We're very fortunate in that there is a specific ICD-10 code for PAP. Autoimmune PAP is 90% plus of all PAP. So we recently refreshed our claims database analysis leveraging a new data source, which is incredibly comprehensive and large. We're talking 100 billion records represented, open and closed source data in this data set. And when you do that analysis, you uncover roughly 6,100 patients with a PAP diagnosis. You take the 10% haircut for autoimmune PAP, and you get to about 5,500 patients now. We torture the data, obviously, because a lot of people can be skeptical of claims data. But again, a very clear marker here, unlike other rare diseases where you're trying to piece together nebulous codes, we have this very good marker in PAP, ICD-10. And what we. That'll be 20 per million by your estimate. It's about 16 per million, depending on what estimate you use for the U.S. population, which is right in the middle of that EPI range that. Isn't there? So I know you've mentioned this. I saw this on your transcript as well, six to 26 per million, the EPI range. I saw very basic lit searches, and I was seeing up to 40 per million. Now, what I can't tell is maybe that's not inclusive of just beyond autoimmune PAP, but conversely, maybe EPI is just all over the place, and we don't know until you get out there and then patients start finding out. I think it's the latter. In fact, Umer, we feel very strongly that over time, you're going to see the upper end. It's not going to be 26 per one million. It's going to be 26 plus x. We believe, for example, in ILD clinics, that there are plenty of, unfortunately for those patients, undiagnosed aPAP patients. Makes sense. I want to sort of get into your clinical data in just a second. But just ahead of that, when I first learned about this from you in that first call we had, my immediate reaction was, well, why not just Neulasta? So could you just speak to, is there any ICD? I know you've done the claims analysis on the ICD-10 for PAP. Maybe the other way around, what if just G-CSF data usage in respiratory indications? Is there anything like that out there on any volume on G-CSF in this indication? Or does it not even work much? It's not worth much. It doesn't work, and is there some clinical data out there? On Neulasta? Yeah, so one of the things I'll say about this is just for a point of clarification: drugs like Neulasta are G-CSF, whereas Molbreevi or molgramostim is GM-CSF, and the M is for the macrophages, so it's more specific and more focused specifically on activating macrophages in the lung. Got it. And does that resonate when you go out to medical conferences with clinicians at this point? Because I would imagine a lot of people fall into that same pitfall as I did early on. Yeah. It does happen. I will say, though, in the pulmonology community, especially on the other side of the New England Journal of Medicine publication of the IMPALA-2 data, there is a really growing level of inquiries and awareness from the pulmonology community about autoimmune PAP, and in fact, we're hearing from physicians that it's heartening them back to their short training on autoimmune PAP in their pulmonology residency, so years ago, a few years ago, there was a little bit more confusion. Now it's become much more clear. Got it. Maybe a quick question for Braden. Could you just remind us the presentation and how easy it is? Yeah. So it's a custom nebulizer built specifically for Molbreevi. And the nebulization time, three to five minutes, soup to nuts, setup, nebulization, and cleanup about 20 minutes overall. But you have the base unit and a handset, which you pour the molgramostim into, and you can nebulize from there. I would imagine, given the construct, this is not something that lends itself to a DPI at any point, correct? No. It will. Because it's MAB-like and this protein stability, et cetera. So this is not okay. But do patients want this as a DPI? Because you don't need multiple puffs a day. Once a day, three to five minutes. Your half-life is what? So do you want to take that? Yeah, so the stability of the drug, its shelf life is about six months. So the actual half-life of the drug in our phase I clinical trial, I want to say that it was 15 days, but I'd have to double-check on that. Oh. So I So I guess, why do patients take it? Do they take it daily in their blood? Yes. It is taken daily. But as you know, the half-life is, it drops off regularly. So you have to take it just to sustain a normal level. How did you guys measure half-life in the blood? Because it's the alveoli concentration that actually matters. Yeah. So that's actually a critical point. Because this is nebulized, it's local. And the actual systemic exposure is quite limited. Right. So I guess how did you measure half-life there? In the phase I study was done in normal patients. They did capture. There was some. Blood exposure. There was some blood exposure. Got it. Got it. So you're saying you did not do punch biopsies? No. Right. Pluck out alveoli in every patient? No. Okay. Exactly. All right. Cool. Makes sense. One last thing, and I want to get into the data again, but we're running short on time. Pricing framework for a super orphan indication like this, what would that be? I mean, I was just hosting a dinner with Apellis last night. They have a drug out for C3G, which is perhaps in a similar ballpark in terms of prevalence pool. They have a price point, I think, around $500,000, for example. But I know there are some others that have been closer to $1 million. So I'm just curious where you guys should go? Yeah. We've done some preliminary pricing work. And not surprisingly, payers don't know anything about autoimmune PAP as they don't typically know about rare diseases. But when you educate them on the burden of illness, they understand it. When you educate them on the Molbreevi data, they get the clinical benefit. And within that research, we identified a range of $300,000-$500,000 per patient per year, at which point we should get full coverage with typical prior auth criteria for access. Now, we've since narrowed that range down to $400,000-$500,000 per patient per year. To your point, we do believe there is pricing power here as well. So this is something that we'll continue to monitor. We have a little bit of time on our hands before potential PDUFA date. We'll see where it goes from there. Okay. Let's jump into the data right away then. Just remind us, DLCO endpoint. What is that? Yeah. So the DLCO stands for the Diffusing Capacity of the Lungs for Carbon Monoxide. And it's a surrogate marker for gas transfer. And it measures how well carbon monoxide binds to hemoglobin in the blood. Did you guys measure FEV by any chance? I believe we did. Exploratory. Yeah, but I don't know that data offhand, but it was captured. Okay. What's important to note is that for patients with autoimmune PAP, most pulmonary function tests are normal. Most pulmonary tests are normal. Do you want to map the underlying? I see. Do clinicians look at DLCO or is that something? Yeah. It is a commonly used. DLCO is commonly used. Yes. Okay. Because look, obviously, you hit all the endpoints you wanted to hit. Primary endpoint, I'm looking at p-value. All that stuff looks good. But part of me is also looking at it saying, on this DLCO endpoint, placebo goes up to about four. Is that percentage or is that four points? Points. 4%. Four points. Yeah. 4%. And the active arm goes up to about 12 points, 10 to 12 points. So sort of the raw number doesn't sound dramatic, but I remember learning way back during my CF experience that if you got those patients to 4% to 5%, it was a game changer in terms of their lung function ability. So I guess just maybe lay out for us what that means, that incremental high single-digit percentage, because it doesn't sound like a big number, but from a lung function perspective and the ability to breathe perspective, it could be something much more dramatic. Yeah. To your last point, it is. And that difference resonates with physicians. I think what you're referring to is the MCID or minimal clinically important difference in terms of what's minimally important difference from a clinical perspective. And what we see here is that while DLCO does not have an MCID for autoimmune PAP, there is an MCID for DLCO for diseases like pulmonary fibrosis and COPD, in which a difference of 10 or 11 percentage points has been found to be clinically significant. And we see that with the study at 24 weeks with a 9.8 difference change from baseline. What indication does the minimal clinically important difference exist for? What indication? For pulmonary fibrosis and COPD, 10% and 11% respectively. 10%-11%. So I guess how do we put the 7-ish%? Or is that just the absolute number? Absolute. It's an absolute difference. Absolute. Yes. What I'm talking about is change from baseline at 24 weeks. That's exactly what you guys are basically hitting in the trial. That's right. That's what we're referring to, and that's what resonates with physicians. I mean, from a clinical trial perspective, we're looking at the difference between the placebo and the treatment group, but what clinicians are looking at is the change from baseline. Yeah. And I think also, Umer, then you tie it together with key secondary endpoints, like SGRQ, for example, where MCID and COPD is a four-unit change. And we absolutely showed distinct benefit there. So you tie that together, and you clearly are seeing a robust clinical effect. Got it. Well, just one more thing. We can look at the percentages and the graphs and look at the numbers off of other trials. But sometimes I find that what patients say in some of these settings matters a lot more. So I'm just curious, anecdotally, from the trials, what feedback did you guys hear from patients that had this? And then how did they feel, I don't know, six weeks out, 12 weeks out, whatever the endpoint is? Yeah. So I think one way to address that question is IMPALA-2 is a 48-week double-blind placebo-controlled trial. We enrolled 164. 159 of 164 completed the trial. Of the 159 who completed the 48-week portion of the trial, all 159 went into open-label extension. Oh, interesting. 100%. So I think that I think you can read through. There is kind of multifactorial. I think there's a takeaway that patients that were on drug were clearly feeling better. Patients that weren't on drug were motivated to stay in the trial to be able to get two years of drug. The third is safety tolerability. There's no safety signal, and patients generally feel good. Yeah. One thing on safety, and by the way, what years was this trial run? Was this run in 2020 during COVID timeframe? We launched first patient in June of 2021, which, by the way, in retrospect, was probably a little crazy. Just ahead of Omicron. Okay. Because I saw there was an imbalance on COVID infections, and I couldn't tell if that's just infected nebulizer at play or something along. We don't know. We've tortured that, and we don't have a good. Were placebo patients taking a nebulizer? Yes. Absolutely. Okay. Because it was, I mean, true blinded. Okay. Got it. Because every other metric I looked at, it looked about the same. But I will say this. As we think about sort of what's clinically relevant and the percentages, there's an endpoint captured in your safety table, which I almost felt like was an efficacy endpoint. It was the alveolar prognosis. I don't even know what the endpoint is and how it's measured, but I do know this. If it's on your safety table, presumably it's clinically relevant. And there was a whole lot more of that prognosis. There was 3x the rate on the placebo arm or the active arm. I guess how's that endpoint captured? And clearly, it was clinically relevant. So it's speaking to something about that efficacy, which is maybe not captured in the way DLCO is captured. Those are the patients that are diseased. I mean, that is the presentation, the continued presentation of. But for someone to say 15% of my patients have this alveolar proteinosis versus only 4% on active, how are they figuring that out? But that's the diagnosis, alveolar proteinosis, right? It's actually what they're capturing is worsening of disease. That's why it looks like that. So that's. Are you guys going to lean into that for label purposes? Because to me, that strikes me as much more of a functional efficacy endpoint than even DLCO is a functional endpoint as well. I'm not diminishing that, but I'm just saying it strikes me as more of a truly measuring what's going on with the disease. You can imagine that sub-analyses that are being done in IMPALA-2 are. There's an immense amount of data, including patients who get worse on placebo over time. That's real, and that's what you're highlighting. Got it. Last point. I know we're at time, but where are we on CMC? We are in very good shape in that we have a hard pivot and alignment with the agency on this hard pivot to Fujifilm as our primary drug substance partner, and we are resubmitting this month with Fujifilm. Do you have your own CMC people who are sort of working with Fujifilm to maintain quality control? Yes. Absolutely. Is that a function you would invest on, you're continuing to invest in for the integrity of this? Absolutely. Okay. Great. Fantastic. Because it strikes me as prime for drug-device combo, and there's a lot of questions. And I've dealt with this with multiple companies over the years. You clearly invested everything you should have on the human factors, and there was no change in presentation. Yes. Okay. Excellent. All right. Fantastic. Fantastic.