... All right, I think we'll get started. Welcome, everyone. Thanks for joining. I'm Dan Kim with the Wells Fargo Biotech Research Team, and really happy to have with me here, Savara. Giving today's presentation will be Matt Pauls, Chair and CEO. Following the presentation, we'll reserve some time for Q&A. So I ask that you hold any questions for the end, and with that, I'm pleased to turn over the mic to Matt.
Thank you very much. Again, I'm Matt Pauls, Chair and CEO of Savara. I want to thank Wells Fargo for the invitation to participate. We're thrilled to be here. Standard safe harbor statement for your consideration around potentially, you know, potential forward-looking statements. Before I begin, introduction on Savara. Savara is a NASDAQ-listed, publicly traded company, a biotech company, focused in orphan rare diseases, specifically in rare lung diseases. And even more specifically, we have a. It's a single-asset company, and we'll talk in more detail about that asset, Molbrivi, or molgramostim inhalation solution. And it is being, has been studied, and we will be pursuing a regulatory approval in the US first, and around the world, for a rare lung disease called autoimmune pulmonary alveolar proteinosis or autoimmune PAP.
So what is autoimmune PAP? Autoimmune PAP or APAP is a disease of dysfunction in the alveolus by macrophage. And this dysfunction creates an issue related to surfactant accumulation. Because the alveolus really it's misbehaving, so to speak, and disallowing the macrophage to chew up and/or metabolize the surfactant. Surfactant can be an oily, viscous material that builds up in the lungs. If not removed, it can cause major issues, such as progressive dyspnea or shortness of breath, which gets worse over time as the surfactant builds up in the lungs and isn't removed.
It can, of course, affect activities of daily living, such as, you know, fatigue and decreased exercise tolerance. There's also very often chronic cough associated with aPAP, and there's increased risk of infection. Unfortunately, for some patients, you know, aPAP that is not adequately or appropriately treated can result in long-term, you know, pretty severe damage such as fibrosis and, in rare occasions, patients require a lung transplant. Serious disease in need of a chronic therapeutic solution. Currently, there are no approved therapeutics in the United States or EU or UK.
There is, though, a rescue procedure called lung lavage, and a lung lavage is done for patients who are often very seriously impaired, and later in the course of the disease due to this rapid and significant accumulation of surfactant in their lungs. Lung lavage is a procedure that is done that effectively power washes the lungs. So patients go into the hospital. They're often in, you know, it can be a lengthy procedure. They often take, you know, a couple of days to recover in the hospital, and there can be, you know, at times, some danger associated with this rescue procedure. This is not the answer, in our opinion, to it. It surely isn't addressing the pathophysiology of the disease.
And it's a. It can be a temporary relief for patients. But we believe that lung lavage will have its place on an ongoing basis as a rescue procedure, but there is clearly the necessity to address the pathophysiology of aPAP head-on. So we have a medicine called Molbrivi, molgramostim inhalation solution. It's a novel inhaled biologic. It is a drug-device combination, and it's dosed once daily, 300 micrograms. Again, an inhaled biologic. We have partnered with Pari, and they have developed a proprietary eFlow nebulizer system that is optimized specifically for Molbrivi as a you know, large molecule inhaled biologic. Pari has a strong track record, and we are proud to be partnering with them over the long term.
It is about a five-minute nebulization procedure, and between setup and clean, cleanup, it's about twenty minutes, again, once per day. So in the end of June of last year, of 2024, we announced the results of our global single phase III investigational study, IMPALA-2, which was a study that enrolled one hundred and sixty-four subjects into a forty-eight-week placebo-controlled a double-blind, placebo-controlled trial. And the results were what we believe to be a winning study. It met the primary endpoint, which was the measure of DLco or gas exchange at twenty-four weeks, stat sig positive, and also some key secondary endpoints were statistically significant or nominally significant. For example, the change in DLco was maintained.
The stat sig result at 24 weeks was maintained through 48 weeks, so durability of effect in addressing directly the pathophysiology of the disease. Also, SGRQ, or also known as St. George's Respiratory Questionnaire, at PRO, was stat sig at week 24, the total score was. Also change from baseline to week 24 in SGRQ activity was nominally significant, and at week 48, a measurement of exercise tolerance or exercise capacity via a treadmill was nominally significant at week 48. Very importantly, the safety and tolerability profile of Molbrivi was resoundingly positive, well-tolerated. Only about 3% of patients discontinued. None of those discontinuations were due to AEs, and 100% of patients that completed the double-blind portion of the trial all enrolled in open-label extension.
Again, 100% of patients. The IMPALA-2 data that I just referenced were just recently published in the New England Journal of Medicine about two weeks ago. Also, the Phase Two/Three proof of concept study, IMPALA, was also published in the New England Journal of Medicine in the fall of 2020. So both IMPALA as well as IMPALA-2, published in the New England Journal of Medicine. Also, recently published was a case series of five aPAP patients who received Molbrivi through a patient access program. And these five patients were on Molbrivi for an average of just over four years. And importantly, prior to starting Molbrivi, four of the five had lung lavage procedures, and after taking Molbrivi, none of the patients, zero patients required a lung lavage.
So real-world experience over the long term with what we believe to be, you know, indicative of positive outcomes for these five patients. The current timeline in the United States is we will be resubmitting the BLA in December. And anticipate after a 60-day review and FDA, assuming that they file the BLA, and also assuming priority review being granted, that we would be looking at a PDUFA, you know, in the third quarter of next year. So, in just about a year from now, assuming all of the aforementioned come to fruition, that we'll be hopefully, you know, being in the process of preparing for launch here in the United States.
In the EU and UK, we have guided to filing the MAA in the first quarter of twenty twenty-six, and you can see projected timelines thereafter. A launch in general in the EU and UK in the first half of twenty twenty-seven. In the United States, importantly, Molbrivi has various regulatory designations, including breakthrough therapy designation, Fast Track, and Orphan Drug Designation. Also, ODD or Orphan Drug Designation in Europe. In the United States, if the BLA is approved, then twelve months or twelve years of regulatory exclusivity will be assigned. Finally, we have you know a few patents that are being prosecuted you know around the world right now. More to come on that.
It should be noted that we have a worldwide exclusive license to the eFlow nebulizer with Pari, and we've also have joint patent application and joint IP with Pari around the drug device combination. From a commercial perspective, the team have been already over the last couple of years, working very hard to help prepare and organize and structure this rare disease market. It, you know, being the first potential therapeutic introduced for aPAP in the U.S., EU, and U.K., there's been a lot of heavy lifting to do to help, again, organize and structure the market.
So raising awareness, building the infrastructure, and bringing on the right people, the experienced people who have been there and done it with regard to, you know, first mover, first launches in orphan rare disease categories like this, it's critical to bring the right people on. So from an awareness perspective, over the last 18-24 months, the team have introduced both a disease state awareness campaign focused on physicians and directed to physicians, as well as a disease state awareness campaign that's directed at patients. It's very clear, based on feedback that we're getting from both physicians as well as patients, that this disease state awareness campaign is having positive impact and helping to raise the volume and level of awareness related to APAP.
We also just almost two years ago in the United States launched a no-charge third-party testing program, antibody testing program for aPAP. When we launched it, we launched it with a serum-based test and approach. Subsequent to that, in the spring of this year, we launched a simple dried blood spot test. A few drops of blood are put on a dried blood spot card that is sent into the lab that we're working with, Trillium. Within seven days, the physician receives the results of either positive or negative and, if appropriate, a titer level. Very simple, in-office finger prick, a few drops of blood, and it's yes or no, 100% sensitive, 100% specific.
This program is absolutely being utilized, and we're getting very good feedback. So when we talk to stakeholders through market research, and you put in front of them the data and the profile related to Molbrivi, what you see here, whether it be physicians, pulmonologists in the United States, payers, and patients, you see a high level of interest and willingness to both prescribe, reimburse, as well as try. This market is in need of a, you know, an FDA-approved therapeutic to help potentially address the pathophysiology of the disease, no doubt. So as of today, Savara has four market development managers out in the field.
These are team members whom, again, have deep commercial experience in helping to prepare and organize and structure rare disease markets. They are currently in the field confirming the claims database analysis results that we have, which I'll talk about in more detail in the next couple of slides. So let's talk a little bit about the epi literature. And so the framing here is that the current literature has a range of diagnosed prevalence from at the lower end of six to seven per one million, and to the higher end of the mid-20s, 25 or 26 per one million. So pretty broad range. And we just recently, as of yesterday, announced that we had rerun our claims database analysis in the United States.
Previously, we had identified approximately 3,600 patients in the United States that we believe currently have aPAP. We enhanced that rerun and reevaluation of the data, and I'll talk in more specifics about what those enhancements were. But the bottom line is, we have identified approximately 50% more patients, or just over 5,500 patients in the United States that we believe currently have aPAP. The comparison here versus the last analysis that we did is that about 300 million lives we analyzed. The data set in this analysis was both open and closed data sources. The previous 2023 analysis was just open source. Many more greater data capture.
So over, you know, 100 billion records were analyzed, compared to approximately 30 billion previously. More recent data and timeframe. So the reporting period was from 2017 to 2025, compared to the previous analysis of 2008 to 2023. And finally, the patient stabilization period, again, more recent, 2023 to 2025. So we also utilized an external third-party data analysis firm to ensure that, you know, we really interrogated these data. And we are highly confident in that in the United States, there's at least now approximately 5,500 patients identified with aPAP. So also we have line of sight, or let me define line of sight. We thought it was very important that we took action related to the claims database analysis work.
And so therefore, our four market development managers and a few of our MSLs have been out, utilizing the data that we have from the claims database analysis. And we're confirming with physicians whom we know, based on these analysis, have diagnosed patients, and we're confirming those patients with them. And currently, as of today, we are at approximately seven hundred and fifty patients or so that we have what we're calling line of sight confirmation of. We'll continue to extend and expand those efforts over the next year or so. But it's heartening when, you know, when you're putting really feet on the ground and you're knocking on doors, confirming that the patients that we know where the patients have been diagnosed and who their physicians are.
In Europe, E.U. and U.K., you'll see a similar amount of projected patients of about 5,200, so similar diagnosed prevalence numbers in to the United States. We also should note that in Europe, specifically, the reference centers are very well known, stocks and flows of patients. The market for the aPAP market in Europe is a well-structured market. And so, we were really looking forward to, you know, driving forward on the MAA submission in the first quarter and driving Molbrivi to a potential approval soon thereafter. Cash runway, we've guided to having a runway into first quarter of 2027, with approximately $146 million in cash as of the end of the second quarter.
We have very strong investor base and support, and as you can see, well covered on the sell side. So in summary, the near and the long-term U.S. market opportunity is significant. Approximately 5,500 patients is the current U.S. total addressable market. We have guided to a pricing corridor in the $400,000-$500,000 per patient per year in the United States. We're prosecuting multiple patents in the United States. If the BLA is approved, 12 years of biologic regulatory exclusivity. And, you know, importantly, we think that over the long term, and given this is a, you know, an inhaled biologic, chronic treatment probably for many patients, you know, unfortunately for them in need of therapy for most of their lives.
In providing physicians a tool, potentially finally, that can help address the pathophysiology of the disease, we're very excited about where we can go with Molbrivi, and in helping the aPAP ecosystem and community around the world. Thank you very much.
Thank you, Matt. Great presentation. Do we have any questions in the audience?
I'm sorry, the question? Yeah, yeah. We're currently in process of-- We've filed patent applications around the world, so it's just the processing of the patents that we've applied for. Yeah. Thank you. Any other questions?
I can ask a few in the minutes remaining. So, you know, can you talk a bit more about your announcement this week on the new health claims data that found over a 50% increase in the estimated number of aPAP patients, you know, what exactly drove that increase?
Yeah, so, you know, I think I don't think it's a coincidence, you know, at all, that over the last few years, as we've invested in the category, disease state awareness, you know, clearly, you know, enrolling or actually over-enrolling the IMPALA-2 trial, and you know, announcing positive results, having those results, published in the, you know, New England Journal of Medicine. Rolling out, you know, no cost, no charge, antibody testing in the United States. You know, when you know, a sponsor or a company starts to invest capital into an orphan rare disease category for the first time, you know, you start to see them come together, and I think that's what we're seeing here.
So, we actually weren't really that surprised to see the increase in the diagnosed prevalence number, you know, in identified patients based on the aforementioned, you know, with the investment and the time and energy that's been put into the category.
Got it. Makes sense. So related to that, you know, you had a presence at ATS. You're going to be presenting more data at ERS later this month. You know, what has physician feedback like been? Just trying to gauge of where we're at in terms of physician education and, you know, how disease awareness has changed over the past few years.
Yeah, yeah. So it has evolved, and it's evolved interestingly around patient symptomatology and disease severity. So, for example, when I first started a few years ago, when you know, we would do market research, or we would have you know, KOL discussions or advisory board. And you know, very often it was natural for physicians to gravitate towards kind of their more difficult-to-treat more severe patients, as you know, potential candidates for a chronic therapeutic like Molbrivi. That's changed a little.
It's changed actually a fair amount over the last few years, and really what's become clear from our perspective is that many physicians will tell us that they will consider offering Molbrivi to all of their APAP patients, their confirmed diagnosed APAP patients, whether they're mild, moderate, or severe. And it makes a lot of sense, even in the mild population, why a physician would want to offer you know, something that you know, like Molbrivi. For example, you know, if you're confirmed diagnosed with APAP, that means that you're symptomatic enough that you sought out a diagnosis, one. Two, we know the pathophysiology of the disease. You need to turn the gas exchange signal back on and help reduce surfactant burden. It must happen.
The earlier in the course of the disease, you know, we think makes a lot of sense rather than waiting till patients get to be moderate or severe. So the bottom line is, what we're hearing from physicians now regularly is they, by and large, are going to offer Molbrivi to all of their, you know, confirmed diagnosed aPAP patients, regardless of severity.
Yeah. So, you know, you mentioned today that you have a line of sight into over seven hundred and fifty patients. I believe it was five hundred as of the last update. So to your point, is it fair to think that, you know, all those patients will be addressable with Molbrivi, given that those patients, by definition, were sick enough to find themselves to a pulmonologist?
Yeah. I want to be careful that, you know, we're not... We don't overpromise here, but I think what's important to note on this line of sight notion is that, you know, in the orphan rare disease, you know, space, when you're relying on claims data, which we have strong confidence and conviction in our data and the analysis, it's also important to go out and do verification too, and make sure that you are understanding, you know, who the clinicians are, starting to establish a relationship, you know, and helping to continuing to educate and re-educate on the disease state, and really it's a validation, quite frankly, of the claims data-based work that we're doing, and it's a key learning.
I think it's a best practice, quite frankly, for first movers in orphan rare disease categories.
Got it. And so, previously, I believe you thought there were those thirty-six hundred patients were located at eleven hundred centers. Does that change with your new analysis?
It's a similar distribution, so the concentration, you know, is relatively similar, which is. We think, relatively speaking, while there is, you know, some kind of onesie-twosie, you know, dynamic in a small portion, we do think that there's relatively a good concentration. And when you look at the heat map, it's intuitive and makes a lot of sense. So there's going to be, you know, real efficiency, we believe.
... Got it. So, you know, what exactly is the process of contacting those eleven hundred centers and gaining a line of sight into actual APAP patients? You know, how receptive have pulmonologists been with respect to your profiling efforts?
They've again, in general, been receptive, been interested in talking about the disease, and growing interest, quite frankly, in the pulmonology community about talking about APAP. You know, I think what's important here is that it's again, it's not a coincidence at all that when you start to put all of these market development tactics into consideration, that you're seeing an increase over the last few years of 3,600 or 3,700 to, you know, 5,500. It's logical. It makes sense. We're really looking forward to, you know, potentially providing a tool for physicians in, you know, addressing APAP.
Gotcha. And then for the undiagnosed patients, you know, do you have similar visibility there, and how straightforward will it be to find and antibody test those patients?
Yeah, so the real question is, you know, how big is the market opportunity? I mean, if you take the 5,500 and, you know, you look at the epi literature, you end up kind of right in the middle. 5,500 comes out to about 15 or 16 per 1 million. You know, and the high end is 25 or 26 per 1 million. I think the real question that, you know, we'll know in 10 years from now, right? Will be, how big really is the APAP market, and what we're seeing is already in the United States growth. So to be determined, but...
Yeah, so related to that, are there any comparable orphan rare disease launches in terms of, you know, the uptake curve, or are you sort of in a pretty unique situation here?
I think it's safe to say it's a unique situation 'cause I think that each orphan rare disease, you know, category and launch is unique. It's difficult to look for, in my opinion, analogs in orphan and rare disease, especially in uptake curve. It's specific to the disease and so there's not really anything that I would be willing to point to. I think it's when you've seen one, you've seen one.
Great, and then on the label, you know, how do you envision the front page to read? You know, what are some must-haves versus some nice-to-haves on the label?
Great question, but I'm not going to speculate on what the label construction or formation will be. But that'll be a great, you know, I look forward to having that discussion if and when, and, you know, we're confident we'll get there, but when that happens. So thank you.
Great, and, we're about to hit time here, but lastly, you know, in August, you reached alignment with the FDA on your BLA resubmission with Fujifilm as the drug substance manufacturer. Is it fair to think that, you know, the in-process testing is mostly complete and shows that it meets specifications?
Yeah, so the pivot to Fujifilm as our drug substance partner on the resubmission does address the RTF issue that was raised previously, so the move to Fujifilm really we feel strongly puts us in a great position on the resubmission.
Awesome. Well, thank you so much, Matt.
Thank you very much.