Great. Well, good morning, everyone. I'm Andrew Fine. I'm one of the biotechnology analysts at H.C. Wainwright. It's my pleasure to introduce Savara, the next company we have with us this morning. They're on the precipice of some very exciting times. So maybe just to kick off, just kind of get everyone up to speed with where things are at, how you're thinking about things, and then we can go on to some specific questions.
All right. Well, thanks, Andrew. It's really great to be here. I'm Dave Laurent, Savara's
Chief Financial Administrative Officer. Good morning. Yasmeen Waspi, Chief Medical Officer.
So I have been with Savara for almost 10 years. And what I can say is in that time, I have never seen as much activity or as much excitement as we have going on at the company right now we're a late stage rare disease company developing a mulbrevi which is an inhaled form of gmcsf treating autoimmune pap and this is something that's been in the work for several years and we and as andrew indicated we are really we're on the cusp we have a padufa date of november 22nd of this year and we cannot wait we have that all circled on our calendars so uh if you think about the opportunity for savara and mulbrevi you know right now there's 5 500 identified apap patients in the u.s and looking at a specialty a rare disease pricing corridor of four hundred thousand to five hundred thousand per patient per year added to the fact that payers have indicated at least 85% have said they will cover Mulbrevy with a simple prior authorization that alone represents a huge opportunity for Mulbrevy and for Savara and if approved it'll this will be the first therapy approved for APAP patients the disease is it's debilitating right now all we have is a whole lung lavage for these patients and that is nothing more than a rescue therapy that Mulbrevy actually will impact the root cause of the disease and a whole lung lavage simply
is a temporary fix great maybe the nice place to start is a little APAP background you know how to patients present you know how well diagnosed is it you know do they tend to congregate at you know centers of excellence or more in the community you know kind of take us through that as because I think you know a lot of the questions at this point are about the commercial opportunity and finding the patients and getting them treated and whatnot. So maybe you can speak
a little bit about that. Sure. Just briefly, so autoimmune pulmonary alveolar protenosis or APAP is a disease that is characterized by the accumulation of surfactant in the lungs. So in healthy lungs, surfactant is a normal substance, but as it's generated, it needs to cleared, and that's normally done by alveolar macrophages. In APAP, patients develop very high titer antibodies to GMCSF, granulocyte macrophage colony stimulating factor, which is essential for normal macrophage function. So as these antibodies bind to GMCSF, it's no longer functional. The alveolar macrophages cannot function normally, And so they're not clearing surfactant, and surfactant builds up and accumulates. So if you can imagine the air sacs of the lungs just filling up with fluid, not surprisingly, the way that patients present is typically with progressive shortness of breath, decreased exercise tolerance. Often they will also have a cough. And one of the challenges is that obviously all of those symptoms are fairly nonspecific. And so patients will often be undiagnosed or misdiagnosed for some time before they eventually get to a diagnosis of APAP. And this can go on for months and even years. And it's because it is a rare disease. You mentioned sort of community versus academic centers. you know many community pulmonologists may not have seen a case and so that may also contribute to some of the delay in diagnosis but but you do see these patients both in community settings and at academic centers what can you do or
what are you doing to kind of increase awareness you know education among some of these physicians that may not have thought about a pap for a while to kind bring it more front and center in their minds.
Yeah, so one of the biggest things that we've invested in is a disease state awareness campaign. And that's actually on two fronts. So it's not only educating the HCPs, but we also have a patient-facing portion of that as well. And look, it's really about deploying the folks that we have. And so right now we have about 25 folks or so already in the field knocking on doors and working with physicians to raise awareness about the disease.
Great. And maybe you can speak about, you know, some of the outcomes that you showed in Impala 2 and, you know, the meaningfulness of those outcomes to physicians and patients ahead of potential commercial launch.
Sure, absolutely. So Impala 2, as you know, was our phase three pivotal trial. We randomized patients to receive daily mulgramostum or placebo and followed them over 48 weeks. The primary endpoint of the study was the change from baseline in DLCO, which is diffusing capacity of the lungs for carbon monoxide, which is a commonly used pulmonary function test to assess gas exchange. How well is oxygen getting from the lungs into the blood? In addition, we looked at other, I guess, more sort of clinically relevant endpoints, including the St. George's Respiratory Questionnaire and exercise capacity. We put patients on a treadmill using a standardized protocol and assessed their exercise capacity. So what the study demonstrated was that mulgramostum was superior to placebo on our primary endpoint of DLCO change at week 24. That change was statistically significant and was maintained in a statistically significant fashion at week 48. And we also showed a statistically significant impact on the SGRQ, the St. George's total score at week 24. And further, we had nominally significant results for the SGRQ activity score at week 24 and for exercise capacity at week 48. So, while DLCO is very helpful because it demonstrates an impact on the fundamental pathophysiology of this disease, these other endpoints, because we showed such consistent results across endpoints, really demonstrate kind of the clinical benefit and the functional improvement in patients.
And maybe to that point, I think yesterday and today at the American Thoracic Society conference, you also had some data and are presenting some data. So maybe you can just speak to that and how it increases the totality of the clinical package.
Yeah, absolutely. So yesterday, Dr. Bruce Trapnel presented results also from the double-blind period of Impala 2 about some different exploratory endpoints related to exercise. So evaluating the distance walked on the exercise treadmill test, as well as the duration of exercise. And on both of those additional endpoints, mulgramostom fared better and with a p-value less than 0.05 at week 48. So I think that's another important, these additional measures that show kind of the functional improvement that patients experience I think were important to share with with physicians today there will be a poster presentation of our open label the first portion of our open label extension results that hasn't been officially presented yet but at a high level it supports continued efficacy of mulgramostum and then additionally we'll have a presentation tomorrow regarding biomarkers results from the double-blind period as well. So again, I think all of these things just provide additional supportive evidence of the efficacy of mulvermostom.
How should people think about disease severity? You know, are there less severe patients and more severe patients? And is one group more or less, you know, motivated to try new therapy? or should people think of it, the group of APAP patients more collectively and be a little bit less nuanced in terms of disease severity relative to potentially trying low glomostum?
Sure. So I think what we have heard consistently, both from our key opinion leaders in the space, as well as in surveying pulmonologists more generally, is that they plan to and would be interested in treating all of their symptomatic patients with APAP across the severity spectrum. And what we further heard from some of our opinion leaders is that part of their motivation is because of their knowledge of what can happen with ongoing untreated APAP. So some of these patients with chronic accumulation of surfactant, even with lung lavage as an intervention, can progress. They can develop opportunistic infections. They can develop lung fibrosis. In some cases, patients even have to undergo lung transplantation. So again, I think we've been hearing very consistently that with a motivation of wanting to do everything possible to potentially prevent those outcomes. There is kind of an interest by physicians in treating kind of across the severity spectrum.
Yeah, and as a data point on the patient side, in the Impala 2 trial, we had I think 122 screen failures. The majority of those screen failed because their DLCO was above 70. So that indicates even in mild patients, they want to be on drug.
That's very helpful. I guess you've spoken about 5,500 or so diagnosed US patients and line of sight into 1,000 patients. Maybe just take people through those numbers and how you're thinking about those.
Yeah, so if you look at the epi data, the range of prevalence in APAP is somewhere between six and 26 patients per million. The 5,500 patients that we've identified, fortunately for PAP, it has an ICD code. And so we were able in 2025 to look at US claims health data and identified 6,100 PAP confirmed patients. If you reduce that by 10% to account for the fact that 90% of PAP is APAP, that's how we derive the 5,500. And then if you compare that to the epi data, that puts it at around 16 patients per million. That's right in the middle of the epi data that we have. So we feel really good about that. And look, we, I mean, we think that's the starting point for us. So from there, we should be able to further educate physicians and build the market. We've also, as you know, have the dried blood spot test. So we have the APAP ClearPath program that's underway. And then, look, once a therapy gets approved, it tends to have increased diagnosis. So we've got great opportunity here to expand the market.
I guess on the diagnosis side, insofar as the antibody test goes, You know, is there a plan to make it part of an order panel at some point, you know, the way, you know, there might be for ILD, for instance, where it just makes it easier for physicians to click a box and get a diagnosis done?
Yeah, I mean, it's possible with the evolution of the program that we could do something like that. I mean, if you remember, we started out with a serum test, which is still available, but There were some barriers at particular doctor's offices around that, and then the next phase for us was the dried blood spot. Basically, you prick the finger, put four drops of blood on a card, let it dry, and send it off to the lab, and within roughly seven days, you've got an answer. So, I mean, we're not stopping, so we're continuing to look at what the opportunity is, and remember, we offer this to the healthcare provider, patient and payers, it's zero pay for them. So this is all covered by Savara.
And I guess that's part of the ClearPath program. Correct. So how have you seen, I guess maybe you can speak a little bit about physician adoption and engagement in the program and how it's kind of going so far.
Yeah, so we haven't given any specific numbers on that, but what we can say is that the ClearPath program is being utilized. I can also comment that, you know, at our ILD clinics, patients are being identified where we've started the pilot program. And then I think the next phase for us is to expand that with some key opinion leader affiliated centers and see if we can continue
to drum up more identified patients. Several years ago, I had the opportunity to go to the Asian Respiratory Society Conference. And it was interesting, particularly among some of the South Korean KOLs, for instance, to hear about, you know, how prevalent they see APAP in their community. And interestingly, you know, some of the KOLs spoke similarly about, you know, like NTM, for instance, and prevalence of NTM in their community as well. And we've seen over time, you know, INSMED speak more and more about the Japanese opportunity, for instance, for our case. Have you at all looked into the Asian opportunity for, you know, an APAP, and how are you thinking about that?
Yeah, so remember that Impala 2 was a global trial, and so we had patients in multiple countries. Of course, right now, our focus is let's get Mulbrevy approved in the U.S. But, I mean, life cycle management is key, and NTM would be a logical place for us to continue to explore.
Great. And I guess, you know, insofar as the regulatory process goes, you know, would Would you, I guess, how are things, are the conversations been constructive? How are things going? And then what steps can you take between now and the PDUFA to kind of ready the market in anticipation of approval?
Yeah, so tackling that first part, look, I mean, we've talked about the fact that our PDUFA date's November 22nd, and that's the result of a three-month extension, right? But when we received that information from the FDA, It was not around safety, it was not around efficacy, and it was not around manufacturing. Basically, as part of the normal process, we received information requests, we responded to those information requests, and the agency deemed that a major amendment, which in essence triggers a three-month extension. So look, it's 90 days. It really is, and I'm a half-cupful kind of guy. it's an opportunity for us to further dive in and identify those patients as really kind of the you know the line of sight program that we've been doing and so we're going to be in a really good place upon approval and then the
other the other part Andrew was it just you know things you can do to ready the
market yeah so like I mentioned before we have 25 or so commercial folks already on the ground that also includes a part of our MSL team and it's continuing that line-of-sight program interacting and really pushing the disease state awareness programs both with the health care providers and the patient patient facing portion of that the more we can identify the more we can test the more opportunity there's going to be both before approval and after because we're going to continue with those programs now what's the latest thinking in terms of an adcom or no adcom yeah so based on the day 74 letter there is no adcom and so that's how we're viewing it and really that's that's just one less hurdle towards approval
but you still feel as though there's the opportunity for you to have the patient voice heard and advocated for in the context of your ongoing conversations without a doubt and that's
that's across the board so i mean literally we'll talk to anybody who wants to listen to us and we genuinely feel we have a path to approvability here so we're going to do everything we can in advance of approval to make sure we give ourselves the the best opportunity for success at
the launch in terms of you know how people should think about the potential curve of the of the launch are there any good proxies you've come up with or a precedential examples that you
might be able to point people towards well I think what I would do is I mean certainly just go take a look at a rare slash specialty launch it's inherent that it's going to have some variables and if you think about specific to Savara upon you know assuming we attain approval on November 22nd we will be launching over two major holidays right we also referenced the fact that payers are willing to cover this but it's under most likely a prior authorization so that's going to take time and then just the inherent getting the patients into the the doctor to get it prescribed we're working with panther as our specialty pharmaceutical or specialty pharmacy they are going to offer you know basically a you know point to point care program for both patients and the physicians so we're doing all the steps that we can to help minimize the up and down variable of getting patients on board and that really should smooth out over the first few months great well I
think we're all out of time but if any final thoughts you'd like to leave
people with by all means you know I'm gonna just revert back to what I said at the very beginning in the ten years that I've been with this company it's never been more active and more exciting and we cannot wait to get this product out into the market for these patients who genuinely have nothing thank you very much all right thank you