Good morning, everyone. Welcome to our Piper Sandler Healthcare Conference. It's day one. My name is Yasmeen Rahimi. I'm a senior biotech analyst. I'm really thrilled to have the team from Savara. I was just saying to Matt Pauls last year at the time we were sitting and discussing the IMPALA-2 readout that was upcoming. My God, what an incredible 2025 you have had, and 2024, and an incredible 2025 that you have ahead. Thank you for being here. I think the first question is for you. Post the positive, strong data from IMPALA-2. You guys have been working diligently on your BLA filing. It's a rolling process. Could you maybe talk about where you are in terms of what has been completed, what's left to do to bring this to the finish line?
Yeah, first of all, thanks, Yasmeen. I'm Matt Pauls, Chair and CEO of Savara. I'm joined by my colleague, Braden Parker, Chief Commercial Officer, newly appointed recently. We're glad to have Braden on the team. Just about five short months ago, we revealed and flipped the IMPALA-2 data card with data that really exceeded our expectations, really across most parameters. Subsequent to that, there has been a lot of work done, including recently we held a pre-BLA meeting with the FDA. Coming out of that, we are initiating the rolling submission of the BLA by the end of this year. In the next few weeks, we will initiate the rolling submission.
And then it's just a short period to complete the submission because we have put a stake in the ground and guided to completing the BLA submission by the end of the first quarter of next year. And so we're looking forward to that. And one side note for this team, our team, we've hit every timeline that we've committed to over the last few years, and we intend to hit this one as well.
How soon post the last module being submitted at the end of Q1 w ould you be able to kind of get an update that it got accepted? Ultimately, talk to us about your expectations around standard review versus priority review.
Sure. Yeah. So here's the cadence. Rolling submission starts by the end of this year. BLA submission will be complete by the end of the first quarter. At that point, the FDA will have 60 days to review the BLA filing. And assuming that they accept it, which we are assuming they will at the end of the 60 days, we will then know whether priority review is granted. Given the fact that we have a breakthrough designation already granted and assigned, we're assuming that we'll also receive priority review, which then would put us at the end of May, beginning of June, and it would then be six months on a roll forward basis from that date for PDUFA, which would put us at end of November, beginning of December. So just about a year or so from right now. So we are assuming we'll have priority review.
Our precedent analysis supports most companies that have breakthrough designation actually do get priority review. So that's our base case timeline.
Then it's an orphan indication, but the question about priority review will also come. Any sense about whether there would be an outcome or not?
We are planning that there will be until we're told otherwise, and we won't know until probably at or around BLA acceptance timeline. But I think it's great practice to plan for it given the fact that Molbreevi will be the first and only therapeutic that could potentially be approved for APAP. So we're planning for it until told otherwise.
Okay. Perfect. I think it's very clear. Investors sitting in this room, others who are listening to the webcast, there's a high POS on our approvability. And I think a lot of the questions that investors ask for us and you are all commercial, commercial related at this point. So I think you guys did a great job of communicating that you identified 1,000 patients that are clear to your site, that you can almost get ready. Could you maybe talk to us? When you say you have 1,000 patients at the time of launch, you have an overview of what kind of information do you have? If you could just talk about what that means for you. Do we have the centers? Do we know the patient names? What do we have access to when we say 1,000?
Yeah, before I turn it over to Braden.
Line of sight, that's correct.
Line of sight, yeah. So one of the work that we're doing now and that Braden has come in and already hit the ground sprinting on is just that it's characterizing what we believe the market opportunity to be, both in the U.S., and what we think to be very underappreciated is Europe. Europe is an underappreciated commercial opportunity for us, which we will be focusing on more starting really now. In the United States, though, again, this notion of orphan rare disease markets where you have first movers like Savara with Molbreevi in APAP often takes time, energy, resource, and expertise to organize and structure these orphan rare disease first mover markets. The good news is that we feel like we have a very good handle today, and it's getting better as time continues to go on, about how big this opportunity could be.
Yeah. And I think Matt raises a really interesting point. I worked in many different rare disease categories where typically the first challenge, particularly in a market where there's no approved therapies, is just being able to find patients. And in this case with APAP, we have identified 3,600 patients today that are known and diagnosed in the marketplace in the U.S. And so when we speak of having 1,000 patients, line of sight to 1,000 patients at launch, it's really about ensuring that we have a rapid and robust launch, really shaping that launch curve to exceed expectations. So as you might imagine, the 3,600 patients that we've identified through claims data analysis, they're known, they're diagnosed, we know where they're being treated.
And so now the process that we're going through is really segmenting the market by account and systematically going through each one of those accounts to have line of sight to the patient, understand how they're being managed, if they're still being managed there or somewhere else, learning about the practice so that we can have a bolus of patients prepared to be able to pull through and again, exceed expectations.
Okay. It would also be great to think about patients that have aPAP. What is their patient journey like once they're diagnosed? How often do they see their pulmonologist? Do they come every three months? Do they come every six months? Because that's going to become also important once the product is available at what point in the patient journey it takes. What have you guys? What has been the frequency of visits for patients?
Before we jump into that, if I could, I want to address something that I think is very important that leads to the patient journey, if I may, and that is the 3,600. So a natural question is, of the 3,600 currently diagnosed, how many do you think would be therapy eligible, r ight? And so I want to take a step back because I think this is very important. This is an autoimmune disease that arguably is therefore lifelong. It's something that patients are going to have to grapple with probably for their entire life, so if a patient has a confirmed diagnosis of APAP, like the 3,600 or so in the United States that we have from the claims database work, that means that at some point they have been symptomatic. If they're not today, they have then, but they probably are today. This is a biology problem.
So they have an issue in the alveolus where they have surfactant burden and surfactant buildup because the macrophage is not behaving the way that it's supposed to. The signal needs to be turned back on. And so whether they be mild, moderate, or severe, we believe, and it's not just our belief, but if you listen to Dr. Trapnell or Dr. Ataya or any KOLs, they will tell you even mildly symptomatic APAP patients should be strongly considered for potentially, if approved, Molbreevi therapy to get started early to reduce surfactant burden. That then leads to the patient journey, which is right now long and arduous. And our job is to shorten that down and help patients get diagnosed earlier and get on therapy earlier. So Braden, do you want to talk about that?
Yeah, and I think the anecdotal information that Matt just shared has been backed up with more robust market research as well that every patient, it appears, will be offered Molbreevi upon approval because of the issues that Matt mentioned, so it becomes a matter of time, right? Having 1,000 patients line of sight at approval doesn't mean we're going to have 1,000 patients in the first month of approval. It's going to take a little bit of time. You mentioned how frequent patients come in to visit. That's some of the information that we're collecting now as we profile accounts to get a good understanding, whether it be at the Center of Excellence or at the ILD clinic or just a pulmonology center, how frequent are the patients that you're managing coming in? Because that's going to be a factor of how the launch curve looks as well, right?
Because coming in, getting assessed, getting the prescription, and then working its way through the healthcare system for reimbursement are all the time factors that are going to determine how many patients come on board each month post-approval.
Okay. Could you maybe give us a color around the breakdown of APAP patients between Medicare and Medicaid? What does that look like? Maybe also talk about where you are with your peer discussions. You've previously commented, obviously, orphan pricing, but there's definitely a ceiling by which you don't want to go up. Yeah.
Sure. So right now, we're assuming the mix to be about 50/50 between public and private. And you referenced some payer work that we've done before that would suggest that within this corridor of $300,000 to $500,000 per patient per year, that we should have reasonably favorable coverage, 100% coverage, the vast majority to just a prior auth criteria to the label and the inclusion criteria most likely as well. But we'll see that as we get closer to approval. And we have some more discussions with payers as well. But it would appear because of the fact that there's a high burden of illness, because there is no treatment alternative, and because of the clinical benefit that we've seen from the IMPALA-2 trial in particular, that payers see the huge unmet need here and don't want to be a huge barrier to patients getting treatment.
They want to make sure that the right patients are getting treatment, so there'll be some of that prior auth criteria, but it looks like an environment that we can work well with.
And most of us, when we get prior authorization, one visualizes just the question of having a confirmed diagnosis. I don't think there's going to be a split of whether you're symptomatic or not symptomatic because you could be non-symptomatic right now, but in a few months you may become. So do you think there is that question comes up as your reason to believe that payers would want to look for symptomatic aPAP patients?
No.
Just diagnosed, yeah, independent of severity?
No. So our working assumption, the base case is that patients, it'll be confirmed diagnosis and/or physician attestation. Pretty low barrier, we believe, for coverage. Again, patients who have a confirmed diagnosis at some point, whether they are now or they're vacillating between being symptomatic, they are by definition diseased and in need of reducing surfactant burden.
Yeah. As is typical in many rare diseases, payers are not very familiar because of the size of the category. And so they lean heavily upon the treating physician and their opinion. So I think with a confirmed diagnosis and strong advocacy from the physician, coverage should be there.
I would love you both spoke about things that are being put in place by the time of launch to ensure to really get as many patients on the Molbreevi as possible. But how do you see the cadence now from January to December, right? What processes are you fine-tuning in the background in terms of the accounts, hiring the sales? Just kind of like you give us sort of like a roadmap on how you're visualizing sort of getting these 1,000 patients identified. What kinks are you working through?
So before I'll have Braden talk through some details over the next 12 months. But I'll say this, that this is a team again that have commercialized, launched and commercialized orphan rare disease drugs. And it's across the enterprise. So what we are working very hard already on doing, and this is even pre-BLA submission, is getting the market ready, starting to prepare patients, accounts, physicians for the potential approval and introduction of Molbreevi. That means that this is the whole notion of it's easy to say under promise and over deliver. It's another thing to do just that. We are aiming to have a bolus of patients so that when we're exiting year one, we're on a run rate that we think is an exciting run rate, helping as many patients as we possibly can in the U.S. and in parallel prepping the E.U. market.
So do you want to talk about some of the details on cadence?
Sure. Well, as you might imagine, about a year away from a potential approval, commercial activities are ramping up quite a bit. But first, I think we should recognize to Matt's point the incredible work that the medical team has been doing led by Dr. Robinson in doing some of the preparatory work on profiling accounts. We now have a couple of medical people in the field as well continuing to work on that effort. And then we'll be looking to bring on a team on the commercial side over the course of the next year. We're doing some sizing work now. And as part of that, we're doing an analysis on the proper time to bring on part or whole of that team. So stay tuned on that front.
We think based on the number of accounts, the number of pulmonologists that will be called on, roughly, again, the work is being done now, but roughly we think there'll be probably 30 or so customer-facing people in the field between sales, sales leadership, as well as adding on to the medical team as well. Because the best way to prepare this market and be ready line of sight to 1,000 patients is really to have feet on the street, as I like to say, and knocking on doors and building those relationships at the account level.
Team, beyond the 1,000, what other activities are ongoing to figure out the 2,600 additional patients that are already diagnosed, right? Between now and end of 2025, is there an opportunity to understand that group as well? And then also talk about the patients that are non-diagnosed as you've been conducting antibody testing. So what activities are ongoing on both fronts, undiagnosed versus the diagnosed, but not the 2,600 remaining ones?
Sure. So just to be clear, we have 3,600 diagnosed patients today of which we're targeting to have 1,000 line of sight to at time of approval. That's not to say we're not going to be trying to get line of sight into all 3,600. We're certainly going to blanket the entire market for sure and make sure that, and I think the awareness will build up with the approval and such that we'll be able to have greater line of sight. When you have more people in the field, they'll be able to call on more accounts and we'll get to that number for sure. You referenced the undiagnosed. So we did some claims data work. As I mentioned before, part of that was using machine learning to identify patients who are likely or highly likely to be APAP just without that formal diagnosis.
Matching the claims history to those that are diagnosed, you get a good sense. You score the different claims history and that's where you get the likely or highly likely category. When you do that, you find another 3,700 patients that are highly likely or likely to be APAP. So a doubling of the market overall. One of the reasons why I was so attracted to Savara and joining the team was because I was impressed with their forethought to really make an investment in the community, build a diagnostic platform that could begin the work of diagnosing those undiagnosed patients. We've launched the APAP ClearPath test about a year or so ago, but really at risk pre-data. We've really focused our effort on that testing now in this ILD pilot, that program that we're running with Dr. Ataya down in the Southeast in Florida.
I think that's a potentially enriched population at the ILD clinics where testing might be more productive. So that launched a little while ago. That should finish up sometime in the first half of next year. We'll see the results from there. Certainly a lot of tests coming in, some positives coming back for sure. We think really that that targeted effort, because it's not an inexpensive test, that targeted effort is really where we're going to bear some fruit on the testing front and really begin to chip away at the 3,700. Our goal is really to expand that pilot program beyond Florida, across the country when we can introduce the dry blood spot test. We're looking to evolve the APAP ClearPath test to a dry blood spot, which is much easier to administer across the country.
Just a few drops on a card, send it in, seven business days later, you have a result. And so we're looking to launch that test in the first half of next year. And I think the combination of that test being available plus seeing the results of the ILD pilot program will enable us to begin to expand that to maybe the next five-10 ILD clinics across the country.
What is the logistics behind? How long does it take now for the antibody testing to occur versus the dry blood? What's the turnaround? What's the?
The turnaround once you submit is pretty similar, but it's just much more of an evolved process because you have to draw blood, you have to centrifuge that sample, then you have to send it in. Not every office has the ability to do that. So we supplement with phlebotomy services. It's just a much more involved process. So the dry blood spot addresses some of those pain points that will enable us to do it much more efficiently and much more broadly.
And I want to just highlight here that what should not be lost to anyone is the fact that we believe we're way out ahead of the game with regard. I mean, this is pre-BLA submission, pre-approval. We have the free diagnostic platform up and running. And we have the fast follower dry blood spot test, which is going to be useful and easy to use for many, many, many years to come to bring new patients into the market. So the intact 3,600 currently diagnosed patients in the United States is a very healthy, well-characterized, knowable market opportunity for us today. And there is real potential near-term upside over the next few years with regard to the 3,700-ish or so that may or may not be able to be brought into the market through our efforts.
That is a sizable orphan rare disease market in the United States, and we're out ahead of it. So at this point right now, it's an underappreciated opportunity. That's fine. It's our job to make it appreciated. And we're in the process of doing that right now. And I think it's really important to note that with this pre-diagnostic program that we have up and running, it's a long game, and we believe it's going to be fruitful.
And you were going to also kick off antibody testing in Europe. Are you planning to kick that off still at the beginning of the year, or do you want to wait until your dry blood test is available and then go on with that? Maybe.
No, we plan to kick it off at the beginning of the year in Europe and make it available.
That has not changed until.
No, it has not changed. Make it available, get the oil running through the European machine as well, and we're absolutely on track for that to happen, so we're looking forward to that as well. Again, the European market is a market that is a well-characterized and structured APAP market, evidenced by the enrollment in the pilot and quite frankly in IMPALA. Robust enrollment, 60+ patients or so currently in the open-label extension across Europe, so it's a robust market opportunity.
What is the size of Europe that you're projecting of APAP? I know there's not really good claims data, but.
Yeah, when you look at the four major European Union markets plus the U.K., we project around 5,000 patients right now. That's based on some work that we've done previously plus the aforementioned trial results as well. And as Matt mentioned, it's a robust opportunity. It's well-characterized. The referral patterns are known. It's a different market, more centralized than we see in the United States, which we think lends itself to a great opportunity. And the numbers that we're looking at in terms of 5,000+ is in line with what you would expect given the fact that there's no founder's effect. And certainly the epi in the literature plus our claims data work in the U.S. would suggest similar numbers over there. So we're confident that there is a big opportunity over there that is underappreciated.
In terms of timing for EMA filing, what is your timing once rolling BLA is completed? When are you projecting?
Yeah, we've guided to filing the EMA by the end of 2025. And then it will be really kind of a regular cadence in Europe thereafter. So priority is BLA filing, get up and running, and then MAA by the end of next year.
Exciting. Next year at this time, we'll be getting close to the approval. So can't wait. I want to say thank you for being part of the conference. It's been a pleasure being your covering analyst. Honestly, I met you when I just joined Piper, and it's been an incredible journey. And what do you guys have done? Congratulations. Can't wait for a great year.
Thanks very much.
Thank you.