Thanks, everyone, for joining us for this year's Guggenheim's Midcap Conference. I'm Vamil Divan, one of the biopharma analysts here, joined by Dana, Dana Cazes, from the team here at Guggenheim. Next in this room here, we have Savara with me here. We have Matt Pauls, the CEO, and also Braden Parker for the CCO. We'll talk about the company as a whole and certainly dig into the commercial opportunity ahead of you guys, so thank you so much for joining us. Matt, I'll maybe just start for people maybe less familiar with the story. If you could give a little bit of an overview of Savara and the path you've taken to here and some of the key recent developments, and then we'll look at the exciting year ahead that you have ahead.
Great. Thank you very much. And again, I'm Matt Pauls, Chair and CEO of Savara, and I'm joined by my colleague, Braden Parker, Chief Commercial Officer. Thanks to Guggenheim for the invitation to participate. So Savara is a single-asset orphan rare disease company focused squarely in the orphan respiratory pulmonary field. We're marching towards an end-of-first-quarter BLA filing, completing the submission of the BLA for Molbrevi, or molgramostim inhalation solution, our novel inhaled biologic where we disclosed positive top-line phase three data from the IMPALA-2 trial last summer. And the company, as a single-asset rare disease company, is focused on getting Molbrevi hopefully approved in the United States and in Europe as fast as we possibly can and getting it into the hands of physicians.
This is an ultra-rare disease, APAP, autoimmune pulmonary alveolar proteinosis, with significant unmet need and nothing approved in the United States or Europe. So Molbrevi would be the first chronic therapeutic. So exciting year and a lot to talk about.
Great. So maybe just, again, to sort of frame the conversation, APAP right now, you mentioned there's no approved treatments. Maybe you can just talk a little bit more about the condition and how people are currently managed.
Yeah, sure. So APAP, or again, autoimmune pulmonary alveolar proteinosis, is by definition an autoimmune disease. It is a disease of macrophage dysfunction in the alveolus in the lung. And it's a gas exchange problem where because there are autoantibodies to GM-CSF that really prevent this or hinder the gas exchange, there becomes a significant amount of surfactant burden or buildup in the lungs if not treated and addressed. And this disease, which probably for most patients is going to be lifelong, chronic, given the autoimmune nature of it, this surfactant buildup causes progressive increased levels of breathlessness, lethargy. It can really hinder activities of daily living for patients as that surfactant builds up in the lungs. And really, what these patients need is they're in need of a therapeutic that addresses the biological problem around this macrophage dysfunction to help reduce surfactant burden in the lungs.
OK. And then you talked about positive data last year. So maybe you can just walk through what we saw in IMPALA-2. And specifically, I guess, as you've been talking to thought leaders out there, what about the data that's especially resonating with them?
Yes. So the IMPALA-2 data is the largest randomized controlled clinical trial in APAP ever in the history of APAP. It was a 48-week placebo-controlled trial, one-to-one randomization. The target was to enroll 160 subjects. We enrolled 164, so slightly over-enrolled it. And the great news is that the primary endpoint, a surrogate endpoint, DLCO, was statistically significant versus placebo at both 24 weeks and maintained through 48 weeks. So the durability around addressing the pathophysiology of APAP was proven through 48 weeks versus placebo, which we were very happy to see the results at 48 weeks. And we were expecting and hopeful that we would see it at 24. So again, longest, biggest trial ever undertaken for APAP. And Molbrevi on the primary endpoint, the surrogate endpoint of DLCO, addressing the gas exchange biology issue in the lung was proven at both 24 weeks and maintained at 48 weeks.
In addition to that, given the fact that DLCO is a surrogate endpoint, there is a need or was a need to show that there was also clinical benefit, that patients were doing better, feeling better, functioning better. And three of the key secondary endpoints were as follows: SGRQ total, a subset of SGRQ, SGRQ activity, and then the third was exercise tolerance test via treadmill. And what we saw between 24 and 48 weeks was SGRQ total and activity were either statistically significant or nominally statistically significant at 24 weeks, both of them. And then exercise tolerance test via treadmill was nominally statistically significant at 48 weeks. SGRQ total and activity numerically maintained separation at 48 weeks. So there was no breakdown there, just slightly missed on nominal stat sig. But the shape of the data, it makes sense. It looks logical.
It held up nicely on SGRQ as well. The bottom line, when you look at the total of IMPALA-2, we are very much looking forward to completing the submission of the BLA and believe that the body of evidence for IMPALA-2 puts us in a really good spot on a path to approvability. I will also highlight the fact that there was a previous phase 2/3 study done called IMPALA, and that those data were also compelling, while not statistically significant on the primary endpoint due to four outlier subjects. Very good supportive data. We have these two very large data sets. Molbrevi is clearly the most studied, researched therapeutic ever in APAP. We're really looking forward to moving it forward as quickly as we possibly can.
So maybe just one more from you then. Just you mentioned filing getting completed by the end of this quarter. Just any sort of risk to that or level of confidence on that? And then more importantly, I think, as you go through the process, what is anything that keeps you up at night as you think about the regulatory process, the things that we should be kind of keeping an eye out for?
Sure. So on track to complete the BLA submission by the end of the first quarter. Absolutely on track. So that's the first. Second is, just as a side note, we also have guided to completing the MAA filing in Europe by the end of this year as well. So that's on track too. Going back to the BLA filing, just as a process note, end of first quarter, complete the submission. Agency would then do a 60-day review. If they accept it for filing, they'll file it. We are assuming at that point that we would also then be awarded priority review, which would put PDUFA then, if all of that occurs as we're planning, end of November, beginning of December, that time frame. So we're on track there.
I think we feel very good based on the results of the IMPALA-2 trial and, in fact, have said consistently that the results actually exceeded our expectations overall, so the unmet need in APAP is unquestionably significant. One, two, there is nothing approved therapeutically for APAP in the United States or in Europe, so the unmet need is significant, and patients are waiting, and so our team are driving super hard to move this forward quickly, and we have a high level of confidence and conviction.
OK. All right. Let me turn to Dana to dive a little deeper on the commercial side.
Yeah, great. Thanks Vamil, so maybe starting in the U.S., you sort of split this opportunity into those that are confirmed, diagnosed with APAP, and those that are unconfirmed, but either highly likely or likely to have the disease. So maybe starting with the confirmed patients, because I believe that's the company's focus right now. You announced recently that you have line of sight to around 450 patients or so out of your goal of reaching 1,000 by a drug launch, by commercial launch. So maybe can you speak to the details of what the company is doing to characterize these patients? And then maybe what you've learned in this process so far that you can apply to the remaining 550 or so patients that you're hoping to get a line of sight to by late this year.
Sure. Oh, I'm sorry.
No, no, no. I just will say up front that Braden has been with us now for four or five months and done a whole bunch of great work. And we're fortunate to have a Chief Commercial Officer who's been there and done it in the orphan rare disease space, both in the U.S. and in Europe. So turn it over to you, Braden.
Appreciate it. Since we're in Super Bowl week, I'll use a football analogy. This is the blocking and tackling of getting ready for commercialization, and so it's really going out and doing the profiling work. I think of it in the context of profiling, getting line of sight to patients, and it's nothing more glamorous than outreach to offices, knocking on doors, setting up appointments, and having those conversations with health care professionals to understand more about their practice. What does the practice size look like? How frequently do patients come in? How are they managing those patients? What's that catchment area, if you will, where patients are coming in to see those physicians in those centers, so that's the work that's being done now to gain line of sight. That's what we mean by line of sight.
It's actually quite remarkable, given the size of the team, really, through Dr. Robinson's yeoman's efforts, as well as a couple of new medical field personnel. We've been able to get line of sight to about 450 patients, about halfway to the goal, as you mentioned. And we're quite confident that we're going to reach and exceed that goal by the time of approval. In fact, we're looking to bring on a market development team early, about 25 folks or so, including leadership. They'll eventually become a sales team. But pre-approval, obviously, they can't promote. So they'll be working on disease awareness, testing education, and expanding our profiling efforts as well to make sure that we're fully prepared for launch.
OK, great, and can you maybe expand on where so far you've found these patients? Are they primarily at these centers of excellence, the ILD centers, general pulmonologists, all the above? Can you expand on that?
Yeah, sure. So as you mentioned, we leveraged the claims data set to really identify not only the size of the market, but where patients are being treated and seen. And so in that effort, there was about 1,100 accounts. We've actually prioritized those accounts to the top 200-250, which, as you mentioned, I'd segment them based on experience treating APAP patients to centers of excellence, interstitial lung disease clinics, as well as general pulmonology centers. We're obviously going out and trying to reach all of those simultaneously, if you will. I'd say the majority of the patients that we've got line of sight to come from the centers of excellence, as well as the ILD clinics with a sprinkle in general pulmonology centers. But make no mistake, we haven't fully characterized all of those COEs or ILD clinics as well.
So there's much more work to be done. But in those top 200 to 250 accounts, there are significantly more than 1,000 patients. So we're quite confident just with those efforts that we'll be able to reach our target. And then, of course, when the market development team comes on board, we'll be able to expand and go deeper not only into the top 200 to 250, but go beyond those to the rest of the targeted accounts that we've identified.
Okay, so maybe moving over to the unconfirmed likely to have APAP patients that you guys said is probably around 3.7 thousand or so in the U.S., so can you maybe briefly expand upon how you're using these claims data and machine learning to get to this number, and then maybe go into the differences between the highly likely population and the likely population?
Sure. Artificial intelligence, such a hot topic these days, right? And so we've leveraged a little bit of that with the machine learning on the claims data set and really looked at the history of those, the claims history of those that are in the system that don't have the formal ICD-10 code. How closely do they mirror those that actually have the diagnosis code? And so we created a scoring system based on how closely they matched. And that's where we came up with the likely or highly likely. The highly likely are those that have maybe a couple of different procedures that you would associate much more closely with autoimmune PAP, for example, bronchoscopy or a lung lavage. And so if you have some of those procedures, you got a higher score and therefore were deemed highly likely versus just likely to have the disease.
But when you couple together both the diagnosed as well as the unconfirmed, you get about 7,300 patients in the U.S. And when you go back to the epidemiology and the published literature, it would skew towards the higher end of that range. And given the fact that there is no founder's effect in this disease, it seems to jibe well with what you would expect in the literature. So we think we're on the right track.
Okay. And then maybe can you discuss? I understand that the confirmed APAP patients are probably the priority right now leading up to the launch. But can you expand upon the progress companies are making towards expanding this addressable market with the rollout of the GM-CSF test, the blood spot test coming out, I think you guys said towards the end of this quarter potentially, and the ILD clinic pilot study?
Yeah, one of the things that attracted me to Savara in the first place was just how forward-thinking the team was. So they launched, and we launched the autoantibody test, serum test, I think towards the end of 2023, early 2024. And really the focus there has been through this ILD clinic pilot program at the University of Florida, thinking that these ILD clinics have an enriched population where you might be able to identify more APAP patients. And that's been the focus with the test to date. And while we haven't spoken about numbers, we certainly feel very good about the path we're on in that regard. And so we're looking to evolve the test, as you mentioned, to a dried blood spot test. We're looking to launch that before the end of this quarter. And the dried blood spot test just offers a whole host of advantages.
It's much easier to administer point of care, doesn't require going to the lab or blood draws, and offers the same convenience of, after pricking the finger and a few spots of blood on a card, you get the results back in seven business days. So the availability of the dried blood spot test, coupled with the expansion of the team, the market development team, and potentially expansion of the ILD pilot program, will enable us to really scale up our testing efforts and begin to chip away at the 3,700 patients that are unconfirmed.
OK, great. So maybe moving to the ex-U.S. opportunity. So you've identified Europe and Japan as markets of interest. Can you maybe go into a little detail on your plans of commercializing in these markets? You're looking to go alone or find partnerships?
Sure. Yeah, no problem. So let's go with Europe first. So we are moving forward full tilt on going alone in the key strategic markets in Europe. We believe that the APAP market in Europe, and again, the major markets, is a well-structured market. We have good line of sight into the stocks and flows of patients, especially given the way many of the countries' health care systems are set up with reference centers, et cetera. Strong enrollment in IMPALA-2 in Europe. So a large number of patients right now in the open label extension on Molbrevi across Europe. And we believe that, again, with the team that we have that have been there and done it, we can go it alone in those key strategic markets in Europe in a, we think, a capital-efficient manner in a country-by-country very bespoke way.
However, in parallel to that, of course, we will remain open-minded with regard to how we commercialize in Europe specifically, and we've also been then Asia Pacific overall, we've been very consistent that for a single-asset orphan rare disease company like Savara, that's often a tough math equation to make work, so we'll, in due time, would be open to and entertain potential partnership opportunities in Asia Pacific, so I hope that helps.
Yeah, definitely. That's very helpful. So maybe expanding on Europe a little bit. As you mentioned earlier, expecting to file the MAA to the EMA by year end. Can you maybe expand on this commercial opportunity a little bit? I think you guys mentioned it was around 5,000 or so patients there. But outside of just the numbers, like how these patients compare to those that we're seeing in the US?
Braden, do you want to take that?
Yeah, going back to an earlier comment, there is no founder's effect here. So we would expect the population size to be very similar in the major markets to the United States. And as Matt mentioned, because of the organization of the market, there's a real opportunity to access these patients, we think, early on. So there's good opportunity over there. There's no real treatment alternative similar to the US. And so all the market conditions in Europe look very similar to the US and a real opportunity to get Molbrevi to patients and clinicians quickly and hopefully treated. We'll obviously have more to say about the commercialization strategy and tactics about Europe as we get closer to the filing and eventually the approval, knock on wood. But we think there is a real opportunity over there.
All right, maybe we've got a couple of minutes left. So just wrap up with some bigger picture questions. So one, if you could just remind everyone on your capital position now and your cash runway.
Yeah, so at the end of the third quarter of 2024, we reported $219 million in cash on the balance sheet and have guided to being capitalized funded through Q2 2027. So we have a long runway. And we're in very good shape on that front.
Then maybe just between now, obviously, the regulatory side's key here as you're getting ready for potential approval and launch. What should we expect from the company just in terms of communicating the progress you're making? You've kind of talked about the line of sight on patients. Anything else we should expect from that on that front or maybe on the blood tests and kind of how you're doing in terms of expanding the potential patient population? So just what should we expect in terms of communication between now and November, December?
Yeah, I mean, clearly completing the BLA submission, completing the MAA submission, the potential for priority review and how that timeline would fit in and shape out the PDUFA date, of course. Dried blood spot test, we think, is again a forward-thinking, getting way out ahead of things and helping to, over the long term, develop the market. So more to come on that. ILD clinic pilot, University of Florida, and the potential for scalability to possibly other ILD clinics in the United States, especially given the dried blood spot test. That could be something that would be, we believe, newsworthy. For example, we just highlighted some long-term open label data of small sample size of five patients who have been on Molbrevi for years, on average, I think, over four years.
I think continuing to stack data and evidence to help both investors as well as, quite frankly, and very importantly, physicians potentially practice better medicine related to APAP.
OK. I think we're pretty much out of time, so I really appreciate you guys coming to the conference, and we'll keep track of the progress.
Thanks very much.
Thank you.