All right. Welcome, everyone. My name is Will Suhikian, and I'm on the Biopharma Equity Research Team at Leerink, and I'm pleased to be joined by the Savara team. We have Matt Pauls, CEO, Braden Parker, CCO, and Brian Robinson, the EVP of Head of Global Medical Affairs. Thank you, guys, for joining us today. We're happy to have you.
Thanks very much.
Great. Yeah, so maybe to start, we could just kind of level set with the folks in the room and get people up to speed who may not be as aware of the story, talking a little bit about the recent progress in 2024 and the kind of milestones that were expected in the near term in 2025.
Sure. Thanks very much, Will. I'm Matt Pauls, Chair and CEO of Savara. Appreciate the invite to participate. Savara is a publicly traded biotech company focused in orphan rare pulmonary respiratory diseases. We have one asset, one therapeutic, novel inhaled biologic, MOLBREEVI. It is soon to be the BLA will be filed, submitted to the FDA by the end of this month for a rare lung disease called aPAP. It's autoimmune pulmonary alveolar proteinosis. We'll talk, of course, in more detail about that. The progress that has been made is that in the middle of 2024, we announced positive top-line results from our global single phase 3 registration trial in IMPALA-2, and again, marching towards BLA rolling submission finalization by the end of this month.
We anticipate, of course, a 60-day review upon completing the submission, given the breakthrough designation that's already been afforded to MOLBREEVI. We're also assuming priority review. That would put PDUFA before the end of the year, late November, beginning of December, to be determined. We are in the very, very exciting time on behalf of the aPAP community in the United States and, quite frankly, around the world. A side note that we anticipate filing the MAA in Europe by the end of this year. A lot happening and a lot of great work and a lot of heavy lifting by the team to do what we need to do to help the aPAP community.
Great. Yeah, no, definitely an exciting time for you guys. Maybe now we can kind of zero in a little bit on aPAP and the disease. Kind of what's the pathophysiology here? What's it caused by? I don't want to say standard of care, but how are these patients currently managed today? Where's the unmet need for those patients?
I'll ask Dr. Robinson to comment.
Yeah, sure, Matt. I'm Brian Robinson. I'm the Head of Global Medical Affairs. Autoimmune PAP, or aPAP, as Matt's already alluded to, is a rare pulmonary disease. It is an autoimmune disease, and there's no known cause of this disease. It affects pretty much everybody, no matter race, sex, age. There isn't a prime age where this disease is focused on, it is between 30 and 50 years old. It doesn't matter where you live. There's no geographic predisposition either. From a pathophysiologic perspective, the challenge is that the body makes antibodies to GM-CSF, which is a cytokine that lives within the alveoli, which are the air sacs of the lungs. This autoantibody binds to GM-CSF that's produced by the lining of the alveoli and prevents it from binding to macrophages, which are responsible for maintaining surfactant homeostasis.
Surfactant is a sort of lipid-proteinaceous material that lives inside the alveoli that keeps it patent. When there is a buildup of this surfactant, there is a deficit in gas exchange. That is what causes the symptoms of autoimmune PAP, which is cough, shortness of breath, and fatigue resulting from the cough and the shortness of breath. Right now, the standard of care, or the only available treatment, I should say, for autoimmune PAP is a procedure called a whole lung lavage, which sounds exactly like what it is, which is basically a washing of the lungs or a power washing of the lungs to remove the surfactant. The challenge with that, from an unmet medical need perspective, is that it is only temporary. It does not address the underlying cause of the disease. Patients require repeat procedures. That is pretty much it, in a nutshell.
Yeah, no, very helpful. Maybe kind of double-clicking on the whole lung lavage, how long are patients getting relief from that? Is it after that procedure, is it an immediate relief, and then does it wane over time? What is kind of the process afterwards, and when are they getting another whole lung lavage?
Yeah, sure. One of the things that's important to note is that it's not a trivial procedure. It's a procedure that's not standardized, and it's only done in specialized centers, primarily. Patients need to be taken to the operating room, put under general anesthesia, and there's a whole team of people who are involved in this process. Saline is basically infused into the lung, and the patient typically gets percussed, like they bang on the sides of their chest to sort of emulsify the surfactant, and then they drain it out using gravity. The patient is usually taken to the ICU afterwards. The effects of it are immediate, but you have to go through this long procedure, and you have to sort of recover from that long procedure. The patient may see the effects.
Now, to answer your question about how long it lasts, that varies. Some patients are faster accumulators than others, but typically, patients will require another procedure at some point in their lives.
Yeah, I think one of the things I'll, if I can add to that, is that when you talk to patients who have undergone lung lavage or lung lavages, they will often describe it as, as you might imagine, traumatic. The recovery is painful and can be lengthy, and really so much so that as they start to accumulate surfactant again, they will do all they can to try to delay or prolong the need to have another lung lavage. They will change their lifestyle. They will become more sedentary. They will avoid things that make them exert effort, given the breathlessness. I think I would not underestimate this notion of it's not a trivial procedure. The second part is lung lavage not standardized, as Brian said, and very importantly, does not address the pathophysiology of the disease. It is not a proxy for a chronic therapeutic.
Great. Maybe just stepping back a bit now and talking about the actual diagnosis of aPAP, we've heard in our checks that this is a process that can take 18 to even 24 months in some cases, or even longer for these patients. Second to that, we were pleased to see you guys launch the blood test last week. Maybe you could talk a little bit about that process and increasing awareness and how that might kind of shorten that diagnosis time frame in an ideal scenario.
Yeah, I'll have both Braden and Brian comment on this. I will say that conceptually, given the fact that MOLBREEVI could potentially be the first chronic therapeutic approved for use, the long arduous process of patients getting diagnosed with aPAP, it actually makes sense. There's never been an investment ever made in this category because there's never been a sponsor like Savara with something like potentially MOLBREEVI. We are now on the front end of that through dry blood spot tests that we just announced last week. We are scaling up right now and going at risk early around our market development team to help get the market structured, prepared, ready in the U.S. This market does need some investment, and it needs organization, it needs leadership.
What we do know is that there are a whole host of patients currently diagnosed, which Braden can talk more about in just a minute. We are highly confident that there are a whole lot of patients in the United States and in Europe and in other parts of the world that are currently undiagnosed. We are determined to change that. Other comments?
Yeah, just quickly about the diagnosis piece. As I mentioned earlier, these patients typically present with this triad of symptoms: cough, shortness of breath, and fatigue, which are, as you can imagine, quite nonspecific. Pretty much we probably all have that right now. It's kind of hard to sort of make a diagnosis. These patients, as you say, typically have an average of an 18-month sort of journey to get to an actual diagnosis, primarily because of those nonspecific symptoms. It's only when they probably get referred to a specialist who may do a battery of tests where they can arrive at a diagnosis.
Yeah, in terms of Braden Parker, Chief Commercial Officer, in terms of the rollout of the dry blood spot test, we're taking a number of initiatives. I think the first thing Matt framed it very well. This is a long-term investment in the aPAP community where we begin to chip away at those patients that are suspected of having the disease but don't have the formal diagnosis.
In the near term, we just launched this in the last couple of weeks here, certainly getting very tactical, updating the website where it can be ordered as job number one, communicating to all of those physicians that have used the serum test previously to make them aware of the dry blood spot test, and then beginning to go out first with the medical science liaisons in the field, ultimately with a market development team that we're building right now to make contact with those that we know have patients now and those that have suspected patients as well over the long term to begin to get testing as part of their kind of treatment algorithm, if you will, especially if they suspect it, to try to shorten that time frame. If we can avoid some invasive procedures and get a diagnosis sooner, that certainly would be helpful. Yeah.
Thank you. Maybe also back to you, Braden, we can talk a little bit more about the number of patients who are diagnosed in the U.S. I think since your top-line data in the middle of last year, you've done a nice job of identifying these patients and having touch points with them. I think you're up to about maybe 450 or so of these patients out of the broader pie. What does the prevalence look like in the U.S.? How has that identification process gone? How do you see it kind of progressing to the back half of this year with the eventual launch?
Sure. The epidemiology in the published literature is a pretty wide range, as is the case in a lot of these rare diseases, anywhere from 6 patients per million all the way up to 26 patients per million, with the latter being a Japanese study where they mandated testing among a population. We obviously wanted to put a finer point on that in the U.S. We engaged in some analyses of claims data where PAP has a specific ICD-10 code. Autoimmune PAP is 90% plus of PAP. Unlike other rare diseases that we all have worked in where it is incredibly difficult to identify patients that might be currently diagnosed today, we have a bit of an advantage in this disease category. That analysis, accounting for the 90% plus cut and some projections, has us estimated at about 3,600 patients today in the U.S. that have autoimmune PAP.
We also embarked on a machine learning component of that database analysis where we looked at the rest of the data set and analyzed their charts and see how closely it mirrors those that have been diagnosed, but they just don't have that ICD-10 code. That yielded another 3,700 or so patients, so roughly in the 7,000 plus range, which, again, going back to the epidemiology, puts us at the higher end of the range, which you would expect. As Brian mentioned, there is no founder's effect. You would expect the prevalence to be similar across regions. Here, at least from this claims database set, we see kind of towards the upper end of the range, which is what we would expect. Now we've begun to take a look at those specific accounts.
All of those patients that I mentioned were identified around about 1,000 accounts. We have begun to go out and knock on doors and profile those accounts and get what we call line of sight into those patients. We suspect a certain account will have a number of patients based on the claim set. We are confirming those numbers now. As you mentioned, we have got line of sight into about 450 of those patients now. Our goal is to be at about 1,000 at launch, which we feel is more than sufficient to get us through the early years of launch and really have that launch trajectory that we want.
Great. Great. I want to spend some time talking about the MOLBREEVI data as well. We were interested to see that this was a long-term manuscript that was published, I think, last month in about five patients or so in Europe that showed some really interesting data over a longer-term treatment that showed reductions in whole lung lavage and some really even some remodeling, perhaps, that's actually getting at the disease itself. Maybe you could talk a little bit about those data. More broadly, what's been the community reaction to the MOLBREEVI top-line data and this manuscript since it's been published?
Yeah, so I'll address that last question first. The reaction to not only the IMPALA-2 dataset and to this manuscript that you're referring to has been overwhelmingly positive. The whole community is excited about it. Patients are excited, and certainly treaters are excited as well. Specifically about this case study manuscript that you are referencing, this is a study of five patients throughout Europe who are treated on the MOLBREEVI Compassionate Use Program, a compassionate use program. I shouldn't say Expanded Access Program. I should say Compassionate Use Program. These patients were on drug for as long as five and a half years. There is sort of a long-term sort of component to this. Across the five patients, it was an average of about four years where they were treated with MOLBREEVI. As you said, the outcomes were quite favorable.
Patients had improvement in pulmonary gas exchange, improvement in quality of life, functionality, and surfactant burden. As you referenced, when you could see their CT scans, you could see the difference between sort of the before and after is quite remarkable. I think one of the biggest takeaways from that is that it gives you a sense of what the long-term effects would be of MOLBREEVI in a real-world setting.
Brian, if you don't mind just commenting on lung lavage pre and lung lavage post in these five patients?
Yeah, sure. Sure, Matt. Out of the five patients, four of them had had whole lung lavages prior to being on MOLBREEVI. By the time this study was published and to this point, patients have not needed another whole lung lavage. We may have mentioned already the whole lung lavage is a rescue therapy, essentially. None of these patients required that rescue therapy.
Great. You also have an OLE ongoing. I think you've had relatively strong transfer from the IMPALA-2 study into the OLE. Maybe you could talk a little bit about that and when we may see additional results from this and what you could show in that.
Yeah, I'll comment and then, again, have Brian comment too. In IMPALA-2, the target enrollment was 160 patients, 48-week placebo-controlled trial. We had, I believe, 286 patients that were screened. To put this in context, there were 286 patients who raised their hand in the midst of the COVID pandemic who were wanting to participate in a 48-week placebo-controlled trial where they had a 50/50 chance of getting nothing. When we first started, we launched IMPALA-2. One of my fears, one of the things that kept me up at night was, can we enroll this? In retrospect, it was a little bit crazy to launch a rare lung disease trial in the midst of COVID. We over-enrolled it on time. We enrolled 164. 159 of the 164 completed the 48-week placebo-controlled trial.
hundred fifty-nine of 159 rolled over into the open-label extension, which then you take a step back, and there's clearly unmet need. I think we can all agree to that based on the aforementioned one. Two, benefit-risk. This is something that I think with MOLBREEVI needs to be really pressed down upon. The fact is that we now have two trials, IMPALA-2 as well as IMPALA, that clearly shows that the benefit far outweighs the risk. This is a tolerable, safe, novel inhaled biologic that is set up very nicely for long-term chronic use for a long-term chronic disease, aPAP. Do you have other comments, Brian?
No, I mean, I think you covered it all.
Thank you. In your kind of earlier remarks, we were talking a little bit about the submission of the BLA. It seems like that's going well. You're on track for completing that rolling submission by the end of this quarter. Can you remind us of kind of which agency division you're dealing with and how it kind of works with the combination product?
It is a drug-device combo. Just to go back, we're on track. Clearly, I think everybody's in the midst of a lot of transition and change and question marks. For us, it is heads down. We're dealing with the pulmonary division, drug-device combo, on track. I think one of the remarkable benefits of breakthrough designation is pre-transition in D.C., it's very notable the engagement with regulators, with FDA, with breakthrough designation. That has continued. Our team is just focused on getting this over the finish line and only controlling what we can control. The drug-device combo, that's important to note here, is that our partner for our nebulizer, our bespoke nebulizer, is PARI. PARI has, I believe, five or six FDA-approved proprietary nebulizers. They've been there and done it. We feel great on that side of the equation.
We're on track and we're marching forward as fast and as hard as we can and high level of conviction around probability of success.
Great. Maybe we can think now a little bit more about the launch and the dynamics there. Of these kind of 1,000 patients that you're hoping to have a line of sight to by the launch, are these all immediately addressable upon the launch? Do you see any kind of segmentation of that market of early adopters? What would make them a good candidate for MOLBREEVI right off the bat? How do you kind of see those things shaking out?
Sure. Oh, I'm sorry.
No, no, go ahead, please.
Sure. I mean, it's difficult to speculate because it'll be somewhat dependent on label ultimately and how it plays out. However, when you look at the marketplace, the majority plus of patients are in that moderate to severe category where they're progressing every single day and heading towards their first or multiple lung lavage. We believe those will be the early hand raisers for MOLBREEVI. We see it both on the physician enthusiasm side as well as the patient side, as we've mentioned before, with not only the trial rollover, but also research that we've done as well. Those will be the early hand raisers. We have heard anecdotally from thought leaders and others that every patient out of all 3,600 plus will be candidates for this product or should be at least offered the product upon approval.
I think that's an important note, too, that clearly moderate and severe makes a lot of sense out of the gate. I think what Braden highlights is an important point, too, that we've heard from physicians that we should not pursue mild patients for early adoption. It makes a lot of sense. If you look at between risk-benefit of MOLBREEVI based on the data, one. Two, autoimmune, probable lifelong chronic disease that the earlier you turn the signal on around gas exchange, right, and get the macrophages doing their job with regard to reducing surfactant burden, the better. While it makes a lot of sense that about two-thirds of the market, moderate to severe, will be early eligible for therapy, we are absolutely for all confirmed diagnosed aPAP patients, MOLBREEVI should be without question should be offered.
If I were a mild aPAP patient and I had breathlessness and chronic cough and fatigue and it was maybe even slowly progressively getting worse, I would want the option.
Great. As you mentioned, it may be a little bit premature to talk about labeling. Could you share kind of some high-level thoughts about labeling and then how that kind of plays into where you're thinking about price range?
I'm not going to speculate on the labeling front. We'll see how that plays out as we go through the regulatory process. In terms of pricing, though, we have done some preliminary work with payers. It's not surprising that payers are unaware of aPAP. It's a rare disease. When you educate them on the disease state, they clearly get the unmet need and the burden of illness. When you share with them MOLBREEVI data, they understand the clinical benefit clearly, especially in the context of having no treatment alternatives other than whole lung lavage, which, again, is more of a rescue therapy.
When you begin to look at price ranges that make sense from a number of different perspectives in terms of getting the value for the product, but also having a reimbursement environment where we can pull patients through, we came down with a range of $300,000-$500,000 per patient per year in that dataset. We think there's some pricing power in that range as well, importantly to note. Most important is within that range, payers were going to cover the drug completely. 87% of them said it was going to be simple prior auth criteria in order to access the drug. We think that is the right environment for ensuring we can get as many patients through the system as possible.
Great. Our discussion here is really focused on the US, which is kind of the near-term focus for a lot of folks, I think. I do want to touch on Europe and kind of ex-US markets. Could you just kind of remind us a bit where you're at with that process and how you're thinking about it? Is this something that Savara could do on their own? Are you looking for a potential partner? What are the kind of strategies that you're thinking about there?
Yeah. One, we absolutely could launch this on our own. There's no question. We could do it in what we believe to be a capital-efficient, bespoke, thoughtful way. We have a team that's been there and done it. We know the market in Europe very well. It is, relatively speaking, a well-structured aPAP market with reference centers, centers of excellence, many of whom participated in IMPALA-2 and enrolled in a really healthy fashion. In the key strategic markets, we could do this in, again, what we believe to be a very capital-efficient way. We're planning. That's the plan. In parallel to that, we also, because we've been there and done it, will be open-minded and pragmatic about what our options are and what we end up eventually ultimately doing.
The great news is with the strong balance sheet that we have that we don't need to go monetize and sell off any part of the world or partner off any part of the world. We get to keep and maintain the whole value for as long if and until commercialization or if it makes sense to do something in a partnership agreement or approach, we'll be open-minded to it. The base case is on our own key strategic markets in Europe. Full stop. We think there's a very underappreciated, very underappreciated opportunity in Europe. We'll change that. Do you want to talk just about prevalence and maybe the opportunity?
Yeah. As we mentioned earlier, there's no founder's effect. You would expect similar numbers as you see in the U.S. across the European continent as well. Our early landscape work has indicated that in the major markets, we've estimated around 5,000 patients or so. That's just in the core EU4 plus U.K.
Okay. Great. Maybe in the last minute or so here, I can ask you about a very fascinating topic, intellectual property. I am curious if you could just remind us kind of what your base case is for that. Kind of do you see other avenues to kind of expand upon that? How should investors handicap that?
Sure. As a point of departure from a regulatory exclusivity perspective in the U.S., of course, if MOLBREEVI is approved and the BLA is approved, that would be assigned 12 years of regulatory exclusivity in the U.S. In Europe, given orphan drug designation, MAA approval would provide at least 10 years of orphan drug exclusivity. In parallel to that, interestingly, because of the drug-device combo and the fact that the device, the PARI nebulizer, is proprietary and fit for purpose for MOLBREEVI, large molecule to be delivered, we have an agreement actually with them for the life of the product that is exclusive. That in and of itself probably provides very long-term protection. We're also, as you might imagine, prosecuting currently joint IP related to the device as well with MOLBREEVI. Stay tuned on that.
Given the fact that it's an inhaled biologic, we think that even if you wanted to prove biosimilarity, probably pretty difficult.
Great. Well, we'll leave it there. We appreciate your time today, guys, and wish you luck ahead of an exciting year. Thank you again.
Thank you.
Thank you.
Thanks very much.