Maybe, just to kick off and just kind of get everyone up to speed with where things are at, how you're thinking about things, and then we can go into some specific questions.
All right. Well, thanks, Andrew. It's really great to be here. I'm Dave Lowrance, Savara Chief Financial Administrative Officer.
Good morning. Yasmine Wasfi, Chief Medical Officer.
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 MOLBREEVI, which is an inhaled form of GM-CSF treating autoimmune PAP. This is something that's been in the work for several years, and as Andrew indicated, we're on the cusp. We have a PDUFA date of November 22nd of this year, and we cannot wait. We have that all circled on our calendars. If you think about the opportunity for Savara and MOLBREEVI, you know, right now there's 5,500 identified aPAP patients in the U.S.
Looking at a specialty, a rare disease, a pricing corridor of $400,000-$500,000 per patient per year, added to the fact that payers have indicated that 85% have said they will cover MOLBREEVI with a simple prior authorization. That alone represents a huge opportunity for MOLBREEVI and for Savara. If approved, 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. MOLBREEVI 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 do 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, kinda take us through that as 'Cause 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. Maybe you can speak a little bit about that.
Sure. Just briefly, autoimmune pulmonary alveolar proteinosis or APAP is a disease that is characterized by the accumulation of surfactant in the lungs. In healthy lungs, surfactant is a normal substance, but as it's generated, it needs to be cleared, and that's normally done by alveolar macrophages. In APAP, patients develop very high titer antibodies to GM-CSF, granulocyte-macrophage colony-stimulating factor, which is essential for normal macrophage function. As these antibodies bind to GM-CSF, it's no longer functional. The alveolar macrophages cannot function normally, they're not clearing surfactant, and surfactant builds up and accumulates.
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. One of the challenges is that obviously all of those symptoms are fairly nonspecific. 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. 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, so that may also contribute to some of the delay in diagnosis.
You do see these patients both in community settings and at academic centers.
Yes. 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 aPAP for a while to kind of bring it more front and center in their minds?
Yeah. One of the biggest things that we've invested in is a disease state awareness campaign, and that's actually on two fronts. It's not only educating the HCPs, but we also have a patient-facing portion of that as well. Look, it's really about deploying the folks that we have. 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. 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. IMPALA-2, as you know, was our phase III pivotal trial. We randomized patients to receive daily molgramostim 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.
What the study demonstrated was that molgramostim 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. We also showed a statistically significant impact on the SGRQ, the St. George's, total score at week 24. Further, we had nominally significant results for the SGRQ activity score at week 24 and for exercise capacity at week 48. 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.
To that point, I think yesterday and today at the American Thoracic Society conference, you also had some data and are presenting some data. Maybe you can just speak to that and how it increases the totality of the clinical package.
Yeah, absolutely. Yesterday, Dr. Bruce Trapnell presented results also from the double-blind period of IMPALA-2 about some different exploratory endpoints related to exercise. Evaluating the distance walked on the exercise treadmill test, as well as the duration of exercise. On both of those additional endpoints, molgramostim fared better with a p-value less than 0.05 at week 48. These additional measures that show kind of the functional improvement that patients experience, I think were important to share with physicians. Today, there will be a poster presentation of our the first portion of our open-label extension results that hasn't been officially presented yet.
At a high level, it supports continued efficacy of molgramostim. Additionally, we'll have a presentation tomorrow regarding biomarkers results from the double-blind period as well. Again, I think all of these things just provide additional supportive evidence of the efficacy of molgramostim.
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 a new therapy? Should people think of it, a group of aPAP patients more collectively and be a little bit less nuanced in terms of disease severity relative to potentially trying molgramostim?
Sure. 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. 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. Some of these patients, with chronic accumulation of surfactant even with whole 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.
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. As a data point on the patient side, you know, in the IMPALA II trial, we had, I think 122 screen failures. The majority of those screen failed because their DLCO was above 70. That indicates even in mild patients, they want to be on drug.
That's very helpful. You know, I guess you've spoken about, you know, 5,500 or so diagnosed U.S. patients and line of sight into 1,000 patients. Maybe just, you know, take people through those numbers and in a, you know, how you're thinking about those.
Yeah. If you look at the epi data, the range of prevalence in aPAP is somewhere between 6 and 26 patients per million. The 5,500 patients that we've identified, you know, fortunately for PAP, it has an ICD code. We were able, in 2025, to look at a U.S. 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. 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. We feel really good about that. Look, we, I mean, we think that's the starting point for us.
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. We have the aPAP ClearPath program that's underway. Look, once you know, once a therapy gets approved, it tends to have increased diagnosis. We've got great opportunity here to expand the market.
I guess on the diagnosis side, and so far 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, for 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, there were some barriers at particular doctor's offices around that. The next phase for us was the dried blood spot. Basically, you prick the finger, put, you know, four drops of blood on a card, let it dry, and send it off to the lab. You know, within a, you know, roughly seven days, you've got an answer. I mean, we're not stopping, so we're continuing to look at what the opportunity is. Remember, we offer this to the healthcare provider, patient, and payers. It's zero pay for them. This is all covered by Savara.
I guess that's part of the ClearPath program.
Correct.
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 kinda going so far?
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 a pilot program. 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.
You know, several years ago, I had the opportunity to go to the Asian Respiratory Society conference. 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. 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. We've seen over time, you know, Insmed.
speak more and more about the Japanese opportunity, for instance, for ARIKAYCE. Have you at all looked into the Asian opportunity for, you know, in APAP? How are you thinking about that?
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 MOLBREEVI approved in the U.S. I mean, life cycle management is key, and NTM would be a logical place for us to continue to explore.
Great. I guess, you know, insofar as the regulatory process goes, you know, how are things? Are the conversations been constructive? You know, how are things going? Then, you know, what steps can you take between now and the PDUFA to kind of ready the market in anticipation of approval?
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 3-month extension, right? You know, 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, you know, triggers a 3-month extension. Look, it's 90 days. It really is, and I'm a half cup full kinda 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.
We're gonna be in a really good place upon approval. The other part, Andrew.
Just, you know, things you can do to ready the market.
Yeah. Like I mentioned before, we have 25 or so commercial folks already on the ground. That also includes a part of our MSL team, it's continuing that line of sight program, interacting and really pushing the disease state awareness programs, both with the healthcare providers and the patient-facing portion of that. The more we can identify, the more we can test, the more opportunity there's gonna be both before approval and after, because we're gonna continue with those programs.
What's the latest thinking in terms of an AdCom or no AdCom?
Yeah. Based on the Day 74 letter, there is no AdCom, and so that's how we're viewing it. Really, that's just one less hurdle towards approval.
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, that's across the board. I mean, literally, we'll talk to anybody who wants to listen to us. We genuinely feel we have a path to approvability here. We're gonna do everything we can in advance of approval to make sure we give ourselves 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 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/specialty launch. It's inherent that it's going to have some variables. If you think about specific to Savara, upon You know, assuming we attain approval on November 22nd, we will be launching over 2 major holidays, right? We also referenced the fact that payers, you know, are willing to cover this, but it's under most likely a prior authorization, that's going to take time. Then just the inherent getting the patients into 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.
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 what, I'm gonna just revert back to what I said at the very beginning. In the 10 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.