Good afternoon, everyone, and welcome to Day 3 of the 43rd Annual JPMorgan Healthcare Conference here in San Francisco. My name is Alex Kramer, and I'm an Associate in the JPMorgan Healthcare Investment Banking Group. It is my pleasure to welcome our next presenting company, Savara Inc. Giving today's presentation will be Matt Pauls, Chair and CEO of the company. Joining Matt for the Q&A portion at the end of the presentation will be Chief Commercial Officer Braden Parker and EVP, Head of Global Medical Affairs Brian Robinson. Following the presentation, we will reserve some time for Q&A, so please ask that you hold any questions for the end. And with that, it's my pleasure to turn over the mic to you, Matt.
Thank you, Alex. My name is Matt Pauls, Chair and CEO of Savara. Thank you for attending today. I also want to thank JPMorgan for the invitation to present. I am joined by my colleagues who Alex introduced earlier. And before we get started, Savara is a rare disease company focused squarely in orphaned rare pulmonary respiratory diseases. Standard Safe Harbor statement with the potential for forward-looking statements for your assessment and consideration. At Savara, we have assembled a strong, experienced, learned leadership team. And if you look across the enterprise, from regulatory to commercial to clinical development, we have brought in a team that have been there and done it with regard to orphaned and rare diseases. And so I'm thrilled to be working with all of them. The company's area of focus is autoimmune pulmonary alveolar proteinosis, which I will refer to as aPAP moving forward.
aPAP is a disease of the lung, and it's a disease of alveolar macrophage dysfunction. It is a signaling issue that is caused by GM-CSF autoantibodies, which block GM-CSF from this signaling that causes a signaling issue that reduces surfactant clearance. So what happens is that in the alveolus, the macrophage can't do its job. And the job is to help reduce and remove surfactant. When that does not happen, bad things happen. With the buildup of surfactant in the lungs, it causes various symptoms, which we'll cover in just a moment here. This is a serious rare lung disease that is chronic and long-term, and it is autoimmune. So unfortunately for patients, they probably will be grappling with it for their entire lives. So symptoms and issues that aPAP patients have to deal with.
First and foremost, the most pronounced is progressive shortness of breath that gets worse over time as the surfactant builds up in the lungs. That is a direct result of the gas exchange problem in the alveolus. Also, fatigue. Often patients will describe that their activities of daily living are impacted negatively. Cough, chronic. Episodes of fever. Increased risk of infection, lung infection that they can't seem to clear, and unfortunately for some patients, fibrosis can result over time, and some patients do require a lung transplant. Unfortunately, again, given the nature of the autoimmune component of this, even with a lung transplant, patients can have a recurrence of aPAP. Another unfortunate aspect of this disease is, there in the United States and in Europe, there is no approved chronic therapeutic that addresses the underlying pathophysiology of aPAP. So what do patients have available?
What do physicians have available? Currently, there is a rescue therapy, so we would argue a kind of a last-ditch effort called whole lung lavage. Whole lung lavage is, in short, power washing of the lungs. It requires patients to go into the hospital. They have to go under anesthesia. They're often in the hospital for a couple of days. They go under anesthesia, and one lung at a time is flooded with saline. There's also very often they have to beat on the patient's chest to help loosen up the surfactant. They use gravity and saline. Again, this notion of kind of controlled drowning of the lung to help remove the surfactant, which you can see on the right-hand side of the slide. There is 20-30 liters of saline often used per lung.
This is a barbaric, painful, often time-consuming recovery process procedure. It is not the answer for aPAP patients whatsoever. And these patients are in need of a biological answer or potential answer to the equation of aPAP. Disease burden is significant. aPAP patients often have much higher rates of healthcare utilization and comorbidities. And here are a couple of quotes from patients. And if you take time to read these at some point, they're pretty alarming and striking, quite frankly. Patients are and the thought of from a patient's perspective of having to have a lung lavage is anxiety-provoking. Once they have one, they often will tell us they never want to have another one. And who could blame them? And with regard to the surfactant buildup and the impact of them on their daily life is significant.
I don't know about you, but when I have breathing issues related to a chest cold, for example, it's scary. I couldn't imagine if someone told me that I had an autoimmune disease and that I was going to have surfactant buildup and maybe have to have a power washing of the lungs to get some relief. Also, unfortunately for aPAP patients, the current journey from the time they start to experience symptoms to being diagnosed is long and arduous. And it takes a lot of work for them to get an answer to the problems that they're facing. The next issue that they face is once they're diagnosed, what do they have available? And right now, it is lung lavage. And on occasion, physicians will try some off-label therapies that rarely work. And at Savara, we're taking this head-on.
We'll talk in detail in just a minute about what we're doing to try to help the aPAP patient community and ecosystem around the world. Our product is MOLBREEVI, or molgramostim inhalation solution. It's a novel inhaled biologic. It is delivered through a proprietary nebulizer, once daily, 300 mcg that's inhaled. It's about a five-minute nebulization time. So between setup, nebulization, and cleaning of the system, it's about 20 minutes once a day, 300 mcg. It is optimized for MOLBREEVI, for the large molecule delivery. Our partner, PARI, is very well respected. And PARI has already five FDA-approved nebulizers based on the same eFlow technology. So strong precedent analysis with our partner and our drug device combo of MOLBREEVI in the eFlow technology. Last June, we were very proud to announce the results of our single global Phase III registrational trial in IMPALA-2.
We believe we have a winning study based on the following results. The primary endpoint of this 48-week placebo-controlled trial was change from baseline at week 24 in DLCO of MOLBREEVI versus placebo. That was statistically significantly positive going MOLBREEVI's way. The secondary endpoints were changed from baseline to week 48 in DLCO. Again, stat sig, so DLCO, which again is proof positive, we believe that MOLBREEVI has the potential to address the pathophysiology, the gas exchange issue in the lungs. Also, we saw statistical significance in a patient-reported outcome, SGRQ total and activity, both statistically significantly positive going MOLBREEVI's way at week 24, and at week 48, exercise capacity via treadmill test, stat sig positive. Very importantly, MOLBREEVI was well tolerated. Only 3% of patients discontinued. So we enrolled 164 patients. We targeted 160, so slightly over-enrolled the trial.
None of the patients who dropped out due to drug-related adverse events. Also, of the 159 patients who completed the 48-week placebo-controlled trial, all 159 patients raised their hand and elected to roll into the open-label extension, 100%. From a timeline perspective, we are in the process right now of working through the rolling BLA submission in the United States. We have guided to having the BLA submission completed by the end of the first quarter. We are on track to achieve that. In addition to that, once the submission is completed in the United States, there will be a 60-day review. At the end of that 60-day review, assuming that the BLA is accepted by the FDA, we are also assuming that priority review will be assigned to MOLBREEVI, especially given the fact that we have breakthrough designation already.
That then would be on a roll-forward basis, a six-month review, which would put PDUFA at the end of November, beginning of December timeframe. In parallel to that, we also intend to file the MAA in Europe by the end of this year. So a lot going on this year. And again, fingers crossed, hopefully, potential hope on the way for the aPAP community. From a regulatory and IP perspective, I already mentioned breakthrough designation, which was assigned to MOLBREEVI, orphan drug designation both in the U.S. and Europe. Also, upon assuming BLA approval, 12 years of regulatory exclusivity in the U.S. We also have a myriad patent estate that we're currently prosecuting around the world. And there's some more details forthcoming on that. Importantly, we have a worldwide exclusive license to the proprietary eFlow nebulizer system with PARI for MOLBREEVI and aPAP.
In parallel to that, we also have pending joint IP that we're prosecuting with PARI for the drug device combination. Now moving to the commercial realm, importantly. In the United States, our commercial launch planning is already off and running. Really, we'll focus for the next few minutes on awareness, infrastructure, personnel, and then diagnostic testing. In the United States, we have already kicked off both a physician as well as a patient disease state awareness campaign, two different campaigns focused on two different audiences. The HCP DSA campaign is intended to have physicians start to think about aPAP much earlier than they have in the past. When they see the gestalt of symptoms that we've highlighted before, breathlessness, fatigue, chronic lung infection, chronic cough, we want them to think about and rule out aPAP much earlier and sooner than they have in the past.
From a patient perspective, we are focused on helping patients shorten their journey, get a diagnosis sooner, and again, hopefully, provide them with a potential chronic therapeutic like MOLBREEVI in the near future. We also are in the process right now of framing out our exclusive specialty pharmacy relationship, a typical best practice in orphan rare disease commercialization in the United States, probably a single specialty pharmacy relationship that will also include integrated patient services, which we'll talk about now. My MOLBREEVI is a best-in-class support program that we're currently developing. It will be a white glove service for patients and caregivers as well as physicians to help support these patients if and when they're started on MOLBREEVI, help them stay on MOLBREEVI, and help hopefully, maybe lessen some of the disease-related burden that they have had to live with.
In the United States, we believe the current day opportunity is significant. We conducted a claims database analysis of 300 million lives. We are confident in the United States, there are approximately 3,600 aPAP patients. We are laser-focused on helping to prepare those patients, again, for the potential approval and availability of MOLBREEVI. There are about 1,100 centers that those 3,600 patients are assigned to through these claims data work that we've done. In addition to that, what we've done is we've kind of decomposed the 3,600. This is an arbitrarily said, we're going to focus on characterizing 1,000 patients of those 3,600 for launch. What does that mean, characterizing? We've termed it line of sight. Gaining line of sight into these patients of the 3,600, we are committed to ensuring that we know where 1,000 of those patients are by launch.
And that's just heavy lifting. And it's knocking on the office doors and confirming with physicians, offices, practices that those patients are, in fact, being treated by that physician at that location. And we are at about 450 or so patients right now that we have line of sight into of the 1,000. And are confident and committed to reaching at least 1,000 by launch. So how are we doing that? Well, currently, we have three members of our medical affairs team who are doing a lot of the heavy lifting. And they're doing a great job. As you can see, we are already at approximately 450. In addition to that, given our level of confidence around the potential for MOLBREEVI being approved, we are starting the process right now of building out our U.S. commercial team of approximately 25 customer-facing field-based team members.
They will be brought on as market development team members. And then, assuming approval on the other side of that, converted to sell MOLBREEVI, again, assuming approval. So that's the how. So we talked about the 3,600 patients that we believe, 3,600 aPAP patients currently in the United States. We also took some learnings from that 3,600 in the 300 million lives claims database work that we did. And we used a machine learning algorithm based on the learnings and teachings from those 3,600 and applied it to the remainder of the 300 million lives. And what we identified was about 3,700 patients in the United States that sure do look like they're aPAP patients, but not diagnosed, either likely or highly likely to be aPAP patients. So that actually looks like 7,000 plus patients probably in short order will be the total addressable market at launch.
We do believe that over time, there's going to be additional patients that we're going to identify as well. So one of the ways in which we are helping to expedite helping new patients, the 3,700 or so patients, to speed up their diagnosis is we launched a free simple blood antibody testing program last year. It's a blood serum program. A physician goes on to our aPAP ClearPath website. They order the kit. The kit gets delivered. They have to draw the blood. It goes through centrifuge. It gets sent back, and they get results, so it is rather labor-intensive, but it is available, and it's free. It's complimentary. It's covered by us, and that was all done pre-data. We went at risk, launched it, got way out ahead, and launched it.
And we are currently using that platform for an ILD Clinic Pilot at University of Florida because we believe the ILD clinics have the potential to be an enriched patient population for undiagnosed aPAP patients, so more to come on that. We'll have results of the aPAP ILD Clinic Pilot by this summer, but we didn't wait for those results to move forward, really, in life cycle management kind of 101, and we developed a dry blood spot test, so the dry blood spot test, we believe, which we're going to launch by the end of March, is a card. And after a finger prick and three to four drops of blood are put on the card, it is sent into the same laboratory that we do our blood serum testing, and physicians receive results within seven days on yes or no, whether the patient has aPAP.
Point of care, much more user-friendly than blood serum. We believe that this is something that over the long term is going to help grow the market significantly. I want to emphasize the current market of 3,600 patients or so is significant as of today. With regard to Europe, we'll talk more about this in the future. Market development in Europe is underway. The opportunity in Europe is real. It is significant. In fact, we currently have over 60 patients in the open label extension on MOLBREEVI in Europe who are eligible carryover patients. The market is well developed, well characterized. We look forward to, again, hopefully, providing MOLBREEVI in Europe for the aPAP community.
Moving on, the cash runway is we've guided to having cash through 2Q 2027, $219 million in cash as of the end of the third quarter of last year, very well funded, and so we are really heads down right now, and the team are driving hard in execution. Bottom line, significant opportunity, huge responsibility that we carry proudly on behalf of the aPAP community with 3,600 patients as of today, pricing power with regard to kind of orphan drug pricing power of $300,000-$500,000 per patient per year, big upside with regard to patients we think that are currently probably have aPAP that are just currently not diagnosed, long, durable potential revenue, at the very least in the United States, 12 years of regulatory exclusivity, probably significantly longer than that. Thank you very much. We'll take Q&A now. Alex?
So I'll open it up to the audience first if there's any. But if not, I can certainly have plenty of questions to ask, so. All right. I'll kick it off. Excuse me. So I guess on that last slide, and you talked about it earlier in the presentation. So I guess first question, just how confident are you in that 3,600 diagnosed patient population in aPAP in the U.S.? And I guess more specifically, what really gives you confidence in that, especially just given how hard it can be to diagnose some of these patients?
I will turn that over to our Chief Commercial Officer, Braden Parker.
Yeah, that's a great question, Alex. Oftentimes in orphan diseases for which there are no approved therapies, it is difficult to identify patients. We're fortunate in this case where we can leverage claims data in order to help identify at least the current prevalent population. And the 3,600, the thing about the claims data that gives us confidence is we've eliminated a couple of the key risks that you often see in claims data. First, was there double counting of patients? And in our claims data set, each patient was given a unique digital identifier, a token, if you will, that made sure that there was no double counting within the data set. And secondarily, oftentimes with claims analyses, there'll be a long lookback period. And you're not quite sure if the patient may even be alive at this point in time.
And to eliminate that, we ensured that patients had to be active in the system within the last 24 months. So they had to have some type of treatment or procedure or something going on that would indicate that they're still alive. And so those two things give us strong confidence in the 3,600 number. That having been said, we also, as Matt indicated in the presentation, are going out and knocking on doors and doing the profiling effort now because we have the location of the patients through the data set. So we're going out to those locations and ensuring that those patients are still being managed by those physicians so we'll be prepared for launch.
Great, and then I guess just another question on that, and again, Matt, you hit on this in the presentation, but can you just comment a little bit more on the progress that you've made in terms of the line of sight to the 1,000 patients at launch? I think you said there was 450 or so right now, so just trying to get a sense of how long it took you to get to that 450 and sort of how that evolves into the 1,000 at launch and beyond.
Yeah, we've made tremendous progress in a short period of time thanks to the incredible efforts of this man, Dr. Robinson, as well as the MSL, this very small MSL team that we have now on the ground doing that profiling work. So we're, as Matt mentioned, about halfway to our goal. We have about 450 patients that we have line of sight into. And we think with the expansion of the field team, the market development team that's coming on board this year prior to approval, we can really ramp up those profiling efforts and ensure that we not only meet but exceed that 1,000 patient goal.
So then I guess what does it take then? And sort of a similar line of questioning, what does it then take to get to 1,500, 2,000? And sort of it sounds like 1,000 might have been somewhat arbitrary of a goal. So just trying to understand how you're thinking about expanding beyond that 1,000.
Yeah, for us, it started with making sure we're efficiently deploying our resources. So I think Matt mentioned there was about 1,100 accounts in the data set for which those 3,600 patients were identified. We took a subset of those, the top 200-250 accounts between the centers of excellence, the ILD clinics, as well as general pulmonary centers. And within those 200-250 accounts, there's significantly more than 1,000 patients. But we took that kind of concerted effort to bite off just enough that we could chew given our current resources in order to start those efforts. And you've seen the results so far with about 450. With the addition of the market development team, we'll be able to expand those efforts, continue to penetrate the 200-250 accounts, but go well beyond those as well.
That gives us great confidence that we're going to meet that objective.
And then just in terms of would love to get your thoughts on why you think aPAP is so underdiagnosed? It feels like something where it's hard to diagnose. It might be hard to reach patients. Obviously, you all have done a tremendous amount of heavy lifting to reach those patients. So why do you think it is such an underdiagnosed disease? I think it would just help everyone kind of contextualize the true prevalence of this disease.
So Braden, before you answer, I'll start us off on this. There's pattern recognition here for me and for many of us around this is going to be the first therapeutic potentially approved for aPAP in the United States and in Europe. So when we talk to pulmonologists, it takes them often a few minutes to kind of get recentered back on aPAP and what they know about aPAP and thinking about aPAP. And when we do that, it's a rich discussion. And you can see the wheels start turning. They don't have anything right now. And the symptomatology, they're nonspecific. I mean, we've said breathlessness, chronic cough, lethargy, lung infection. Sounds very familiar, right? So we believe that with Savara out in front with MOLBREEVI, the promise of the potential of MOLBREEVI, that's going to change the game.
We feel so strongly that we've already launched free simple blood antibody testing. Anything more?
Yeah, I think I'll take this one, Matt. So I think it's an interesting question to talk about the epidemiology. The published literature says that it is between six and 26 per million, and that's based on really three studies. The closer to the lower end, the six-seven per million is from a U.S. analysis and also a Japanese analysis. On the higher end, the 26 per million is from another Japanese paper that required mandatory testing of patients. So these patients were just basically coming in off the streets. And they had to have a test. And then it was determined that they were positive for this disease. So there is quite a range.
But I think if you take into consideration the 3,600 that Matt spoke about that are the known patients that we know about, plus the machine learning patients who are probably those patients who are walking around who are undiagnosed, that equates to about 7,300 patients. So that takes you toward the higher end from an epi perspective. So I think that's why we think this is underdiagnosed in addition to the comments that Matt made.
Yeah, no, that makes a lot of sense. And then switching gears a little bit and just talking a little bit more about the regulatory side of things. So I think you had initially indicated you'd file BLA in the first half of 2025. Obviously, you initiated the rolling submission in December late last year and indicate you'll be completed by the end of the first quarter this year. I guess what changed that enabled you to be able to potentially complete that filing in the first quarter? And how confident are you in sort of that deadline that you've set out for now?
So first, I'll take the last part of the question first. The BLA will be completed. The submission will be completed by the end of the first quarter. So that's going to happen. So that's one. The second is why did the timeline shift? It went from 1H 2025 to end of first quarter of 2025. That was just simply small company making sure that we were going to be able to do what we say we were going to do. And when we felt strongly that we were going to be able to deliver it, we tightened the timeline down. That's it. Full stop.
Got it. And then I guess the other piece of the equation, I know we talked a lot about sort of the patient population. So obviously, the other side is sort of pricing. On that last slide, it looked like $300,000-$500,000 is what you've indicated. So I guess what gives you confidence in that price? And what gives you confidence that it'll be covered at that price?
Braden?
Yeah, we've done some preliminary research on pricing. And not surprisingly, similar to other orphan diseases, the payers are not very familiar at all with autoimmune PAP. But when you educate them about the condition, the burden of the disease, the clinical benefit of MOLBREEVI, as well as the fact that there are no approved therapies out there, they begin to understand that picture for sure. And looking at analogs, looking at other factors, we were able to create a pricing corridor of $300,000-$500,000 per patient per year, as you saw on the slide. Within that pricing corridor, the feedback has been we will get full coverage of MOLBREEVI post-approval. And in fact, they're looking to provide full coverage. 87% of them say it's going to be simple prior auth criteria in order to receive the drug.
So that gives us a high degree of confidence that we're in the right range. We'll obviously put a finer point on that as we get closer to approval and announce a price. But we do believe that we have pricing power within that range and that we'll have great coverage and a good reimbursement environment for MOLBREEVI post-launch.
And then just one more question from me. And I know you hit on it a little bit in the presentation. And I know you said there would be more forthcoming. But just anything else you can share just in terms of the EU market opportunity? I think that'd be helpful, but.
Yeah, sure. Braden?
Yeah, there is no founder effect here. Unfortunately, it's an equal opportunity disease, and so you would suspect that the number of patients over in Europe would be similar to the United States. And at least our initial landscape work would suggest that as well, so looking at the major markets in Europe, the EU4 and the U.K. now, and doing some of that preliminary research, it looks like there's roughly about 5,000 patients that we estimate within that group of five countries. Obviously, a tremendous amount of work needs to be done there, but we do see, maybe because of the nature of the health care system there, a more concentrated market where there's more predictability in the stocks and flows of patients to major centers.
And so that gives us a degree of confidence that, like the United States, we could have a capital-efficient commercialization strategy over there as well as we have over here. So more to come on that once we file at the end of this year and get closer to a potential approval and launch.
And then I guess just last question for me. I guess if there's anything to leave with us as sort of a takeaway as you look ahead into 2025, obviously, a lot of great things, hopefully, in the near future. So just any other closing thoughts that you'd like to leave everyone with?
Yeah, thanks, Alex. I want to emphasize the commitment of this group of people at Savara is significant. We take our responsibility to the aPAP ecosystem and community very seriously, and I am really proud to be working with this group of people, and we are doing everything we possibly can to get MOLBREEVI in the hands of physicians as soon as we possibly can to provide them a real, tangible, chronic therapeutic that could potentially change.