All right, we're just about ready to kick off, guys. Thanks for joining us for day two of the Citizens Life Sciences Conference. My name is Jon Wolleben, analyst here, and we're pleased to have Savara joining us, and Matt Pauls, CEO, Braden, Chief Commercial, and Brian, head of- Medical Affairs. Medical Affairs, which is the perfect team to be talking about an upcoming potential launch with molgramostim, MOLBREEVI, for a rare pulmonary condition that has got a very high unmet need. Matt and team, thanks for joining us today. Thanks, John. On behalf of Savara and the team, we're appreciative of the invitation to participate. You know, it's been a long time coming. You guys are in front of FDA now with your package. Maybe can we talk a little bit about PAP to start, to kind of set the table for what you guys are doing. Sure. Before I ask Dr. Robinson to opine on autoimmune PAP, I'll just give a brief overview of the company, if that's helpful. Savara is squarely focused in the orphan rare pulmonary respiratory space. As John mentioned, our lead candidate that's currently under review by the FDA with an August 22nd PDUFA date this year is MOLBREEVI. It's on the heels of positive phase III data in autoimmune PAP. Brian? Yeah, sure. Thanks, Matt. Just briefly, autoimmune PAP or autoimmune pulmonary alveolar proteinosis, as the name suggests, is a rare autoimmune pulmonary disease that affects pretty much everyone globally. There's no predilection for age, sex, race, socioeconomic status, or region. It does have a sort of sweet spot of discovery between the ages of 30 and 50, but it's been found in patients as young as three and as old as 90. Basically, in this disease, the body produces this autoantibody to a cytokine that's produced actually throughout the body, but specifically in the lung, called GM-CSF. These autoantibodies bind to GM-CSF and prevent it from binding to macrophages, which are a key cell within the lung alveoli, which is sort of this gas exchange bubble at the terminal end of the lung. This GM-CSF normally binds to macrophages and allows macrophages to maintain the normal level of surfactant, which is this thin, sort of oily substance that keeps the alveoli patent, keeps it open. When these autoantibodies bind to GM-CSF, preventing it from binding to the surface of macrophages, the macrophages can't do their job to maintain the normal level of surfactant. The surfactant builds up in the lungs, and this causes the symptoms, which are shortness of breath, cough, and ultimately fatigue. These patients typically are immunocompromised, so they may have a superimposed infection. Also, when they do a CT scan of the lungs, you will see this classic appearance of ground glass opacification with crazy paving. Although not pathognomonic for autoimmune PAP, it's very suggestive. That along with the symptoms that I mentioned. Can we dig in there a little bit? 'Cause when you say shortness of breath, cough, fatigue. Hmm Doesn't sound that bad. Talk to us about the morbidity with the disease. It doesn't sound that bad, John. As you might think, it also is pretty much every single pulmonary disease out there presents that way, so it's hard to actually ultimately diagnose the disease. Because of that, these patients are kicked around the healthcare system for an average of 18 months, and there's a morbidity associated with that. The patients ultimately can't perform their daily activities. As I mentioned, they're more susceptible to infections, and these patients are pretty debilitated. Yeah. I remember, we were talking to a guy who has it, and he was a marathon runner, and then he was saying he couldn't get up the stairs. He was just too exhausted. How is it treated today? What are the options for folks? They're limited, quite frankly. There's a lot of supportive care with supplementary oxygen. There is a rescue procedure called the whole lung lavage that's available, and it sounds like exactly what it is. It's basically you take the patient to the operating room, you put a double lumen endotracheal tube, you respirate one lung, and you wash the other lung with warm saline. You do upwards of 30 or 50 mL of warm saline to do that. While you're infusing it, you're banging on their chest and moving the patient up and down to emulsify the surfactant that's in the lungs, and then you drain it out. As you can imagine, this is a pretty barbaric procedure. Patients hate it, and actually, the physicians who perform it also hate it. It's not standardized across centers here in the U.S. or even globally, and it, as I mentioned, it requires significant OR time, significant OR staff, and it doesn't address the underlying pathophysiology of disease, so that's one of the challenges. It needs to be repeated. The fact that that's even an option speaks to the morbidity of the disease that people were willing to undergo that. How does MOLBREEVI work? As I mentioned earlier, there's this autoantibody that the body makes to GM-CSF, and while the body makes its normal GM-CSF, the idea of MOLBREEVI, which is a recombinant GM-CSF that's inhaled once daily, is that it overwhelms the antibody. One of two things are happening. Either it's binding directly to the antibodies that are in the space or it's binding directly to the macrophages to activate them to turn on the signal and allow the macrophages to do their job. Pretty elegant, you know, replacement strategy. Very elegant, very straightforward. talk to us about the data you guys have generated, 'cause you mentioned we got an August PDUFA, but, you know, what about, you know, how confident should we be in approval based on what you guys have shown? Yeah. Again, I'll have Dr. Robinson comment, but before he does. IMPALA-2 is the single global phase III registrational trial that we have filed the BLA and MAA recently in Europe based upon. It's the largest study and the longest study in the history of autoimmune PAP. We enrolled 164 subjects in a 48-week double-blind placebo-controlled trial. Of the 164 patients who enrolled, 159 completed the 48-week double-blind placebo-controlled study portion of the trial, and of the 159 that completed the trial, 159 or 100% all enrolled into the open-label extension. We are confident that we have a path to approvability based on the results of the study. It was a winning study in the primary endpoint, which is DLCO. And it won at 24 weeks, beating placebo, stat sig, and then was maintained through 48 weeks statistically significantly better than placebo, so it showed durability of effect. Then I'll have Brian comment on the key secondary endpoints of SGRQ total, SGRQ activity, as well as exercise tolerance test via treadmill. Yeah. Thanks, Matt. One of the things that's important to keep in mind is that this, the IMPALA-2 study really addressed all of the cardinal manifestations of autoimmune PAP, namely surfactant burden, challenges with gas exchange, respiratory quality of life and the way patients function, so patient functionality. As Matt mentioned, our endpoints captured this. The gas exchange piece is captured by DLCO, which was statistically significant at both 24 and 48 weeks. Our respiratory quality of life with SGRQ, which stands for the St. George's Respiratory Questionnaire, which is a questionnaire that's used frequently in pulmonary disease, that captures how patients feel. The data was excellent with that, with being statistically significant at 24 weeks and maintaining good separation between the placebo and the treatment group at 48 weeks, for both the total score and the activity score. Then lastly, with exercise capacity, which was done using an exercise treadmill test where patients were put on a treadmill and they had to walk, and then there was elevation, like typically what you think of with a treadmill test. These patients did very well, and throughout the entire study, the 40-week study, there was good separation between the placebo group and the treatment group, and it was statistically significant at 48 weeks. I think, John, the key here too is that, you know, with DLCO as a surrogate endpoint winning at both 24 and 48 weeks, and then through the key secondary endpoints of, you know, SGRQ total activity and the exercise tolerance test, you know, when you take the totality of the evidence, it's you know it's very clear that, you know, we believe that, you know, MOLBREEVI's addressing the gas exchange issue and the clinical benefit is, you know, evidenced again by the results from SGRQ, as well as exercise tolerance test. As a final note is that these data were published last summer in The New England Journal of Medicine. Yeah. You mentioned this, Matt, but I think retention is one thing that we always look at as kind of where the rubber meets the road. If patients are staying in a trial that's much, you know, longer and extended, they're perceiving or having a benefit. But when you guys look at the totality of data, you talk to physicians and the patients at the sites, is there a difference in goal of treatment between the pulmonologist treating them and the patient? Do they care about the DLCO more than the patient feeling? Or like how do you think of, you know, what's resonating with the different audiences if it is different? I mean, I'll just say that patients ultimately feel better and Matt sort of testified to that when he talked about how the patients who completed the double-blind period and then rolled over into the open-label extension. Half of those patients were getting placebo, but they were eager to get on MOLBREEVI, and the patients who were on MOLBREEVI stayed on it. I mean, it was blinded, so they didn't know. Mm-hmm. This sort of is a testament to unmet need. Patients feel better, and the actual numbers, the data supports that, across both how they feel and function with the SGRQ and the exercise tolerance test. Yeah, DLCO was important because that was sort of, that measures the gas exchange, and patients were able to breathe better. Mm-hmm. All of these things taken together sort of speak to the, you know, patients wanting to be on this, on this drug, and we're hearing that anecdotally. I wanna make sure we have plenty of time to talk commercial because I know that's where a lot of investor focus is. We got the August PDUFA, the other black box that we have in our seat is always CMC, and I know you guys have worked hard on that front as well. Can you give us an update on kind of the review package and what you guys have done in manufacturing? Sure. Coming out of the RTF about a year ago, approximately just under a year ago, we were able to get alignment with the FDA around an analytical comparability protocol for a tech transfer to Fujifilm. We were successful in that. We then at that point had to produce the data to fulfill said analytical comparability protocol, which we did, then resubmitted the BLA. As you know, just a short time ago, the BLA was, you know, accepted and filed by the FDA, priority review granted. Just last week, day 74 letter received and no Ad Com. It was a hard pivot to Fujifilm, and we resubmitted the BLA with Fujifilm as the drug substance partner. We're fortunate in the team, you know, we had some forethought, you know, a couple of years ago about, you know, tech transfer. We didn't address this, but the logistics of using MOLBREEVI. Talk to us about that. With regard to, you mean the administration? Yes. Yeah. Yeah. It's once a day. All in, it's about 20 minutes. That includes setup and then nebulization or inhalation of three to five minutes and then clean up. Again, once a day, all in about 20 minutes, low burden. Do people see like an immediate benefit? Is there a recommendation for when in the day they administer it? It's not like an inhaler like Primatene MIST or something like that. Mm-hmm. It doesn't work like that. When you look at our data, you could see that there's that separation between the placebo group and the treatment group starts at around eight weeks to 12 weeks. We think that sort of, it's sort of I mean, if you think about it sort of intuitively, there needs to be a gradual opening up and allowing the GM-CSF to bind and for the macrophages to turn on. Mm To start clearing the surfactant. It's not an immediate kind of thing. It takes some time. Got it. Pivoting to commercial, you guys have done a lot of work here 'cause it's a rare disease. There's nothing approved. The investment community, you know, did not really know much about it. Talk to us about, you know, how, you know, your prevalence estimates have evolved over time and where we are today about patient identification, launch strategy, all the good stuff. Yeah, sure. I'll give a quick setup on the epi literature, and then I'll turn it over to Braden. In the current epi literature, the range of diagnosed prevalence at the low end is about six or seven per 1 million, and at the high end is about 26 per 1 million. That's what the current literature. It's a pretty broad range. We've done claims database work in the U.S. over the past few years, a couple of rounds, and the most recent evaluation of the U.S. claims database work yielded a number that puts the U.S. diagnosed prevalence right in the middle, right down the middle of the fairway, 15 or 16 per 1 million. Braden, do you wanna take that? Sure. Yeah. We're very fortunate in this disease state where there is a specific ICD-10 code for PAP. Autoimmune PAP makes up 90% plus of it. Unlike other rare diseases where you're trying to piece together these nebulous codes to try to figure out market sizing, here we have a pretty good marker with the ICD-10 code for PAP. We engaged with Veeva Compass Patient, which is a very large data set, 300 million lives represented, 100 billion records or so, open and closed data sources, to put a finer point on the epi literature. As you might imagine, it's a pretty big range, and it's not very, it's pretty typical in a rare disease to see a range like that in the literature. We wanted to put a finer point in the US. Engaging in this claims database, working with a third-party analytics company, we went into the data set, identified patients with the PAP diagnosis, and did a number of other things to make sure that we had confidence in the data. When you do that, you come up with a number of about 5,500 prevalent patients in the U.S. We think that's the new floor. As Matt mentioned, it's right in the middle of the epi range in the literature. To make sure that, you know, we had a high degree of confidence in that number, we did a few things. We made sure that each patient was tokenized, so they're unique and not double counted. If we found the code in the system, we had to make sure the patient was active. It's not like we found a patient in the system, and they're no longer with us. They had to be active within the system between the beginning of 2023 and the middle of 2025. Just sort of having DOGE flashbacks about this. Yeah. Exactly. We made sure of that as well, that they were active patients in the system. We also put on some additional clinical analytics, whether it's multiple codes or multiple pulmonology visits, to make sure there was no miscoding in the system. Between all of that, as well as the robustness of the data set, we have a high degree of confidence in the 5,500. How about you've talked about kinda line of sight. You know, talk to us about pulmonologists. How many are they? Is everyone under the care of a pulmonologist today, or is it you go for the referral, we don't have much to do for you, go back to primary care, and you kinda get back in the system? Like, what about identification and actually knowing where they are? Yeah. Well, as Brian mentioned, unfortunately, patients get bounced around the system. It's typically to a pulmonologist and then maybe varying pulmonologists at expert centers ultimately before they get the diagnosis. When we look at the data set and we do our targeting efforts, we've identified about 1,700 key accounts that we want to target with the field force and roughly between 4,000 and 5,000 pulmonologists primarily that we'll be calling on with our field force. There is a degree of concentration in this marketplace. Mm-hmm. The top 500 accounts manage roughly 2/3 of the patients when you look at the data set. We think and believe that we can effectively and efficiently address the market with a field size of roughly 23, what we call rare disease specialists, tack on some leadership on top of that, so you're in the 30-ish range for the marketplace. As you mentioned, what we've done is we've gone out first with the leadership team and soon with this field force that'll be joining us in the second quarter and done some profiling work. People can sometimes be skeptical of claims database work, so we went out and knocked on doors to confirm that the patient was still being actively managed at these locations that the claim came in from and they were being actively managed by the physician who submitted the claim. In that work, through a brief period of time, we did get line of sight to roughly 1,000 patients, which was our goal by the end of last year. Mm. Now, that work obviously continues until we, you know, are there with all 5,500. But again, it was a confirmation of what we believe to be the floor of the marketplace. You guys are doing a really good job with the blocking and tackling to prime the system. Can you talk a little bit about the testing that you guys are offering? Because we talk about diagnosis being an issue, but then also doing a journal paper, you can get out and do some education. Like, what are you guys doing now ahead of the launch to make sure everybody knows what's going on? Yeah. Well, there's a couple of things that we're doing. One is we've had an ongoing physician focus disease state awareness campaign, which we've, we, you know, are amplifying even more right now. That is about making sure that the pulmonology community is thinking about autoimmune PAP much earlier when they see this cluster of non-specific symptoms that they see regularly, right? There's another important piece to that, and that is we've also equipped and made available for physicians in the United States a no-cost, simple, dried blood spot card antibody test. With a few drops of blood after a finger prick on a card, they can send it in and within seven days get a yes or a no. Also a titer level to be able to rule in or rule out, again, at no cost, if they suspect that a patient might have autoimmune PAP. You know, as you might imagine, that's not part of the 5,500 of the currently diagnosed. That is how big is the market, right? How is it 15 or 16 per 1 million, or is it 26 per 1 million, or does it end up five years down the road being, you know, 26 plus X? We have and we're way out ahead of it on this, you know, simple no-cost diagnostic testing program. I think I always ask you, and I think you never tell me, but what can you tell us about kind of tests coming in, kind of positive rates, and if not now, will you ever be talking about what you're learning there? We're not providing specific numbers on that just for pretty simple reasons. You know, it seems to be never seemingly never enough, and then you get asked all the time. The bottom line is the test is being utilized in the United States, and newly diagnosed de novo autoimmune PAP patients are being identified. We actually have it specifically focused in an ILD clinic pilot at University of Florida that is currently in the process of being expanded to multiple sites around the country. We think ILD clinics and actually have validated that at University of Florida is a place where, you know, many patients with these cluster of non-specific symptoms that many of, you know, whom potentially could have autoimmune PAP are being seen. We've been focusing on U.S., but you mentioned that you submitted your applications ex-U.S. Talk to us about that relative opportunity and how you think about commercial launch prep work there. Sure. Yeah. We just recently filed the BLA or the MAA in Europe, and soon will in the U.K. The base case is that we plan to go it alone because we can. We have the balance sheet and, you know, very well capitalized, and we've contemplated going it alone in Europe and U.K., and we will to maintain full control and full value of the asset, quite frankly. We will march it forward. We're doing all of the blocking and tackling to prepare for potential approval, and then, you know, sequential kind of typical country-level sequential launch. In parallel to that, you know, monitoring very clearly Most Favored Nation, you know, evolution and how that, you know, may or may not play a role in, you know, timing, et cetera. What's really important, of course, is that, you know, until there's additional clarity on that policy, you know, we need to make sure that we don't encumber or hinder the U.S. launch. You mentioned it. Like, you talked about this pricing range, 'cause that's the other equation of the puzzle when we think about commercial opportunity. Where are you at today about, you know, potential pricing bands that you're testing? Yeah. In the U.S., we've done quite a bit of work on that front and have previously talked about a pricing band of $300,000-$500,000 per patient per year. We've since narrowed that range to $400,000-$500,000 per patient per year, just given the strength of the data, as well as the feedback we've gotten from payers overall. Within that pricing range, the feedback has been that there's limited concern about budget impact for payers and that there'll be coverage with typical prior authorization criteria. We have a high degree of confidence in that pricing band. We mentioned we got the August PDUFA commercial launch prep. We'll be staying tuned this summer for potentially the approval. Can you remind us of cash position where you guys are to fund the launch, and if you need to do anything ahead of that, or you know, how we should think about you know, top line growth and cash spend, that trade-off? Yeah. Last report, $264 million on the balance sheet. We also have a royalty arrangement agreement upon FDA approval of $75 million royalty deal with RTW. We also have a $75 million debt facility at our discretion upon FDA approval arranged with Hercules. Up to $150 million in non-dilutive capital available upon FDA approval on top of last report of $264 million on the balance sheet. With a sales force of about 30 reps, 20, 30, I think you said? Yeah. 23 RDSs with about four leadership team members on top of that, so 27-ish. Perfect. Well, August is gonna come sooner than we know it, so I appreciate you guys coming and spending time with us and telling us about the story. We're looking forward to a potential launch later this year. Thanks very much. Thanks. Thanks, guys. Appreciate it. Thank you.