Almost on schedule, which is pretty good for day two.
Welcome, everybody, to the Citizens Life Science Conference 2025. My name is John Walden. I'm a senior analyst here, and I'm pleased to have Savara joining us with CEO Matt Pauls and Head of Corporate Access, Brian.
Brian Robinson.
Brian Robinson.
Global Medical Affairs.
Global Medical Affairs, which we're going to talk to you a lot because now the rubber hits the road here in just a few short months. Maybe to kick off, Matt, can you tell us, for those not as familiar with Savara, what are you guys working on? What's your mission? What's your strategy?
Yeah, thanks, John, for the invite, and also to Citizens again for the invitation to participate. Savara is a rare orphan respiratory pulmonology-focused company with a single asset and a novel inhaled biologic called molgramostim inhalation solution. We are currently actively pursuing FDA approval for a rare lung disease called autoimmune PAP, which we'll talk about in detail. That is on the heels of our IMPALA-2 phase III results that we disclosed at the end of June last year. We are marching forward very, very quickly on that front. We are anxiously, excitedly, and hopefully awaiting potential approval by the FDA, assuming that we get priority review by the end of this year. In parallel, we'll be filing the MAA in both Europe as well as in the U.K. by the end of this year. Exciting, exciting times.
Can we talk a little bit, maybe to set the stage about autoimmune pulmonary alveolar proteinosis, you know, what it is, how many patients, unmet need, and that kind of set the stage to then talk about molgramostim in your clinical program?
Yeah, sure. I'll have Dr. Robinson provide an overview on aPAP, and then we'll talk about the unmet need and market.
Yeah, sure. Thanks, Matt. Autoimmune pulmonary alveolar proteinosis, or autoimmune PAP, as I'll refer to it, is a disease manifestation of a broader syndrome called PAP, or pulmonary alveolar proteinosis. aPAP, or autoimmune PAP, that's a lot of word salad, but an alphabet soup. aPAP is a chronic rare autoimmune disease where patients, for unknown reasons, develop autoantibodies to GM-CSF, which is a cytokine that lives throughout the body, but has a specific role inside the lung where it activates macrophages. Macrophages are these blobby cells that live inside the alveolar space. The alveoli are the air sacs at the terminal end of the lungs that are responsible for gas exchange. That's where the air that you breathe interfaces with your circulation, and gas exchange occurs there.
The challenge with autoimmune PAP is that these autoantibodies bind to the GM-CSF that's within the alveoli and prevents it from binding to the surface of macrophages, not allowing them to mature. One of their key functions is maintaining the right level of surfactant that lines the inside of these alveoli. At the interface between the air and the circulation, there is a membrane that surrounds the alveoli, and there's a surfactant that lines the inside of these alveoli that maintains the patency of the alveoli, keeps it open, and allows gas exchange to occur. When these autoantibodies bind to GM-CSF, not allowing macrophages to maintain the right amount of surfactant inside the lung, there is a buildup of surfactant, which blocks gas exchange. That's really what the problem is.
This manifests with shortness of breath and resulting fatigue and a cough because you have all of this material or gunk, if you will, is the technical term that's built up inside the alveoli. This is what causes sort of the triad of symptoms, which is cough, shortness of breath, and fatigue. That's kind of the background of this disease.
I think the big question that a lot of people have is how many patients are there? I want to dig into kind of commercial prep and launch strategy there, but just prevalence-wise, how many do you think there are?
Yeah, so the [EPI] data, there are a few sources, and there's a range around diagnosed prevalence estimates. At the low end of the range, the [EPI] literature would suggest that it's approximately six or seven per one million. Currently, the higher end of the range is more like 25 or 26 per one million. There are a couple of data points, you know, clearly in between there. In the United States, based on claims database work that we have done now a couple of times and reanalyzed of approximately 300 million lives in the United States, we've identified about 3,600, 3,600 currently diagnosed patients. We also used a machine learning algorithm that took the teachings or learnings from those 3,600 patients and applied them again to the remaining 300 million, the same data set, claims database.
We identified about the same number, 3,600, 3,700 patients that look awfully like the 3,600 based on symptomatology, but they are either undiagnosed. We think the currently diagnosed market of approximately 3,600 in the U.S. is clearly robust and a very, very healthy, you know, addressable patient population for us to commercialize into right at launch. We also think that clearly, especially if you go back to the EPI literature and the range between 6 per 1 million and 26 per 1 million, there's a whole bunch of patients out there that are currently undiagnosed. It's not surprising, given the fact that we and MOLBREEVI potentially could be the first approved chronic therapeutic for the treatment of autoimmune PAP. Like many other first movers in orphan rare disease categories, there are a lot of patients that appear over time once you have an approved therapeutic.
We're already starting to see that as we prepare the market for launch.
Because when you think cough, fatigue, shortness of breath, that could be me if the escalator is not working. Can you talk a little bit about kind of actual severity of the disease, heterogeneity of those patients? You know, how are they treated today? How many do you think would actually want therapy? Kind of like the actual consequence of having aPAP.
Yeah, so if you think about right now, if you're a patient and you are experiencing chronic, you know, progressively worsening of breathlessness, that's scary stuff, and you don't have an answer for it. You have chronic fatigue, probably cough that's just persistent. Maybe you have weird, you know, pulmonary lung kind of infections that don't quite clear all the time because you have, you know, a good breathing ground there. You find your way somehow to a pulmonologist who actually, you know, maybe it's one or two or three of them that think of aPAP. You have to figure out how you get tested, how you get diagnosed. You know, there are some very invasive ways that patients unfortunately have to get diagnosed.
There's also some very simple ways, for instance, the dried blood spot test that we just recently launched to help patients, you know, through a 100% sensitive and specific diagnostic to speed that up. If you're currently diagnosed, you're sick enough that you found a way to a pulmonologist who then helped you figure out what the heck's going on. You're probably very open to trying to find a way to reduce your surfactant burden. Whether you deem yourself or your doctor as mild, moderate, or severe, that's almost kind of irrelevant because here's the reality is it's never going away. You need to turn the signal on and reduce the amount of surfactant that's building up. That has to happen straight away or things get worse over time.
Can you talk about how molgramostim works and then the clinical data you guys have shown, what that means for patients? Because in my mind, we've been tracking the story for quite some time. This is kind of a no-brainer that the trial was going to look good. I think it looked better than even we were expecting. Can you talk a little bit about what you guys showed?
Sure. Yeah, happily. A little bit about how molgramostim works. You know, I mentioned that there is this autoantibody that binds to GM-CSF inside the lung in patients who have autoimmune PAP. In the case of molgramostim, it's an inhaled recombinant GM-CSF that patients take once a day using a proprietary nebulizer that is bespoke for molgramostim itself. With this inhalation, essentially the antibodies are overwhelmed by the exogenous GM-CSF that's being introduced into the body and allowing for some of it to bind to the macrophages to, as Matt says, turn on the signal. That's essentially how it works. It's pretty straightforward. I guess the best kind of analogy is kind of like a replacement therapy of some kind. I think that might be an easy way to think about it. That's essentially how it works.
In our clinical trial, basically, it showed that, just a little bit of background on the clinical trial itself quickly. The IMPALA-2 trial is the largest, the longest randomized clinical trial ever conducted in this disease. We enrolled 164 patients globally in 43 centers over 16 countries. This was a 48-week double-blind study where patients were randomized to either get molgramostim or placebo, taken once daily. To your point, the primary endpoint was the change in DLco from baseline. Just quickly, DLco stands for the diffusion capacity of the lung for carbon monoxide. It's a surrogate measure of gas exchange. It really just measures how much carbon monoxide binds to hemoglobin. That's a marker for how gas exchange occurs between the air that we breathe and the bloodstream.
Just noting that difference between the placebo and the treatment group at 24 weeks was the primary endpoint. There were some key secondary endpoints, namely the DLco at 48 weeks. There was an important patient-reported outcome called the SGRQ, or St. George's Respiratory Questionnaire, which is a measurement of essentially respiratory quality of life. There was an exercise capacity measured using an exercise treadmill test. All of these parameters sort of made up the outcome of this study. Essentially, as I said, the primary endpoint was this DLco at 24 weeks. That was statistically significant at 24 weeks. It was also statistically significant at 48 weeks, which showed a durability of effect, which has a lot of clinical relevancy. That is one of the key aspects of the IMPALA-2 trial.
Not only did we hit on these key endpoints, but there was also a clinical benefit for patients. That was, you know, kind of something that was, you know, an amazing surprise and something that we were really, really excited about. The study was kind of a roaring success, I would say.
Yeah, and I would just add to that too that, you know, well summarized, but I would just add that, you know, so objectively via DLco measurement on the primary endpoint, addressing the pathophysiology of the disease, because it's known, it's very clear that MOLBREEVI had a stat-sig impact compared to placebo at both 24 as well as 48 weeks, tied together with clinical benefit, right? St. George's, the SGRQ total and activity, as well as exercise treadmill test, either at 24 weeks or at 48, there was stat-sig separation and/or strong numerical separation as well. When you tie it together, we believe it's a compelling profile for aPAP patients. Now, also on benefit risk, it's really important to note that 164 patients were enrolled. 159 of 164 completed the 48-week double-blind placebo-controlled trial.
Incredible, right?
One hundred fifty-nine rolled into the open label extension, every single completer. If you look at the safety tolerability profile of MOLBREEVI, the benefit risk of MOLBREEVI compared to placebo and in general is very apparent.
Phase III, check. You completed your rolling BLA submission. Check, wait and see if that gets accepted. I imagine it does. It's not a few days now that we don't hear something about the sky falling at FDA and regulatory reviews and rare disease and all the above. Can you talk a little bit about the review process, the team you're working with, any kind of FDA interactions, how things have been going so far? As you're starting this process, any concerns you may or may not have?
Sure. As you said, John, rolling submission was completed at the end of March. There is a 60-day review period by the agency. That puts us at the end of May around file acceptance. Technically, it is then the agency files it. We are expecting, first of all, priority review, given the fact that we have breakthrough designation, et cetera, but that has not been communicated yet. We are expecting that. If that is the case, we at that point would have a six-month roll forward, which puts us at the end of November for PDUFA. Just as a side note, given the fact that this is the first therapeutic ever reviewed for autoimmune PAP, we are planning for, until told otherwise, an adcom. We will see.
There's a whole host of other things that go along with that with regard to the agency and their ability to do that. But we're planning, like I think, you know, good smart teams would do. There have been no hiccups for us. You know, we are under review by DPAC, which is under the CDER division. But things have been moving right along. But we'll see. You know, who knows? You know, we have no crystal ball, neither do you. But as of today, it's status quo. And that's all we can control.
We should be hearing sometime soon on the acceptance and then some details on prior review, adcom, indication.
Yes.
Okay.
Yes.
Can you talk a little bit about your payer research, understanding of unmet need? Again, I'm guessing there needs to be some education on all fronts. Talk a little bit about those discussions, pricing bands you guys have talked about, because when we hear, you know, this number of patients, there's a wide fluctuation, obviously depending on what's out there, the clinical benefit you guys are showing. How does that all tie together?
Sure. Let me start with how are patients currently treated, which, and then we'll kind of work backwards from that. One, there is a rescue procedure called lung lavage. That's where when patients have significant surfactant buildup and accumulation and their breathing becomes very labored and, as you might imagine, lifestyle and health in general are, you know, potentially significantly impacted, they go in and have, you know, often one, at least one, if not both lungs, power washed with 20-30 liters of saline. They're in the hospital for a couple of days. They, you know, try to use gravity to help remove some of the gunk. That is a rescue procedure that is no fun. It takes a long recovery and it's surely not a chronic therapeutic. There's some off-label drugs that are thrown at the condition that are utilized.
Pivoting to payers, our conversations with payers are, one, when you put a product profile, educate payers on the disease of aPAP, and then you, you know, tell them about lung lavage, et cetera. It's rather appalling to them, as you might imagine. Then you put the, you know, the product profile based on the results of IMPALA-2. Then you cross-reference that with price points and talk through, you know, what we believe to be some of the potential, you know, potential health outcomes and benefits, et cetera. We landed in a price range right now where we're guiding to comfortably $300,000-$500,000 per patient per year. Yes, that's a broad range. We do believe in that band, there is clearly pricing power that we have.
Sensitivity grows as you go higher in the price range, of course, but we think that that is a very reasonable sensitivity range for modeling purposes. Payers, almost 90%, I think 87% said they would pay. They would cover it in that range. As you might imagine, it'll be standard in commercial plans, standard, you know, specialty tier, prior auth, proof of diagnosis. We'll have a single specialty pharmacy that'll adjudicate all of that and work through to get patients both on as fast as possible and keep them on.
Expectation primarily commercial coverage for people affected by aPAP or Medicare?
You know, we think out of the gate, a safe assumption is in, you know, on the commercial front, you know, conservatively 50%-60%, maybe more like, you know, 60%-70% on the commercial front. That's the way to think about it. You know, patients now currently are getting diagnosed later, kind of, you know, fourth or fifth decade of life. As you might imagine, we're going to do everything we can to pull that forward earlier, so.
How should we think about a potential launch here, first approved drug for the indication, relatively, I'd say, low awareness, but you guys are working on that. Can you talk about kind of the antibody testing that you guys have out there? You've teased a little bit about kind of tests coming in. You might tell us, you know, what those have looked like. I don't think you have yet, but anything you talk about on those metrics. When you say 100 patients rolled over to your study, can they go right on commercial drug on day one? You know, how do we think about a ramp here? What are realistic expectations?
Right. Shape of the curve, right? That's the big question, like how fast do you get out of the gate and what does it look like? Is it low and slow up and to the right? The great news is we think that we have credibly, appropriately set this up to hopefully, you know, hope's not a strategy, but to hopefully exceed expectations. Let me break that down a little bit. One, we have, you know, dried blood spot antibody testing program up and running. We have currently a single ILD clinic pilot at the University of Florida that's ongoing. Yes, we've held back on both testing numbers as well as as a side note on EAP.
Do you want to tell us today?
No, actually, because here's the problem. It's never enough, right? I think we can agree with that. It isn't, and that's fair. I get it. At the right time, there might be an opportunity to provide some more clarity on that. Stay tuned. The ILD clinic pilot clinic that we have up and running at the University of Florida, we're going to scale that up to other ILD clinics. It's very clear that that is an enriched population of patients who are undiagnosed. That's the undiagnosed kind of longer game pilot program. With the dried blood spot, a few drops of blood, send the card in, you get a yes or no and a titer level in seven days. You know, it's pretty user-friendly. Our confidence on the potential for this opportunity has continued to grow, and it's grown significantly.
In fact, we are in the process right now of, by the end of, or by the middle of the year, so end of June-ish, having approximately about half of our market development team hired and out educating, re-educating pulmonologists, reminding them of aPAP. Also, you know, highlighting the fact that we have dried blood spot tests available and confirming line-of-sight patients and making sure that we know that, you know, we continue to, our confidence continues to grow, that we know where the patients are, who the doctors who are diagnosing and treating them. That is all pre-approval so that we can hit the ground sprinting.
The blocking and tackling. Matt, in the last minute or so, can you remind us of your cash position? You know, where does that get you? Through approval, but what do you need to launch this drug successfully? Do you have that in-house or are you going to need to bolster the coffers a little bit?
Last report, $196 million in cash on the balance sheet. Recently, we just announced a debt refi of our small, about $30 million in debt. We leveraged that in partnership with Hercules to create a future non-dilutive option of up to $170 million in a mezzanine structured, you know, debt financing approach. $40 million upon approval, $40 million, if we want to draw it down, up to $40 million at approval, up to $40 million, you know, within six months after that, another $20 million based on a kind of a low bar revenue threshold, and then $70 million at kind of mutual discretion if we want to. The setup's there. The guidance on current balance sheet is that we have cash through second quarter of 2027. As you just talked about, there's plenty of.
Yeah.
Yeah, with regard to the current setup.
Near term, we should be hearing about FDA acceptance, prior review, adcom, potential approval later this year, and a lot of discussion about launch prep between now and then.
Yes.