Okay, we're going to get started. Thanks for tuning in. My name is Andrew Tsai, Senior Biotech Analyst at Jefferies, and next up is Savara to my direct right, Matt Pauls, Chairman and CEO, and to his right, Braden Parker, Chief Commercial Officer. Welcome, both of you.
Thanks.
Thanks.
So maybe spend a couple of minutes talking about the Savara story for those who might be less familiar. Briefly walk us through your program, where you are, and milestones coming up.
Yeah, thanks, Andrew, and thanks to Jefferies for the invitation to participate. So Savara is a single-asset rare disease company focused in the rare pulmonary respiratory space. Our single asset is MOLBREEVI. It is a novel inhaled biologic, and it is being studied for, and we reported out at the end of June, positive phase III data for a rare lung disease called aPAP. And aPAP is autoimmune pulmonary alveolar proteinosis, but we will refer to it as aPAP for the rest of the presentation. As I just mentioned, at the end of June, we reported positive phase III results for our IMPALA -2 study. IMPALA- 2 was about a three-year study. It enrolled 164 subjects. We intended to enroll 160, so we slightly over-enrolled it.
The primary endpoint measurement is DLCO, and the primary endpoint measurement in the IMPALA- 2 study was at 24 weeks, although the study was a 48-week placebo-controlled trial. The results were what we believe to be resoundingly positive and, in fact, exceeded our expectations, which we'll talk in more detail about. We recently, in third quarter earnings, reported that we had a successful pre-BLA meeting with the FDA. Subsequent to that, given the fact that MOLBREEVI has breakthrough designation, we will start the rolling submission by the end of this year. We'll complete the BLA submission by the end of the first quarter. Assuming that priority review is granted, we anticipate PDUFA in the United States to be really by the end of 2025, so at or around December 1.
Lastly, last two things about third quarter earnings report is that we also have guided to filing the MAA by the end of next year. And lastly, on the financial front, we reported $219 million on the balance sheet, and we extended the cash runway. It is now through the end of 2Q 2027. So there's a quick sketch.
Wonderful. And to level set things, how big is the aPAP market? What kind of peak sales opportunity are you thinking about in just the U.S. alone? And feel free to talk about worldwide as well.
I'll ask my colleague Braden Parker, our new Chief Commercial Officer, to opine on that.
Thanks. When you look in the literature at the epidemiology, there's quite a wide range from six per million all the way up to, I think, 26 per million. So we embarked on a claims database analysis to get better clarity on the size of the U.S. market. And through that analysis, using ICD-9 and ICD-10 codes, we identified 3,600 patients in the U.S. that are currently diagnosed. So rather a large opportunity that are known diagnosed patients. We understand where they're being treated, how they're being managed. And so we're approaching those accounts now and will be continuing from now until launch.
Additionally, within that claims database analysis, we did some additional machine learning that looked at the rest of the patient population within the claims analysis and tried to match those that had a similar looking profile claims history to those that were diagnosed. They just didn't have the actual diagnosis. And doing that, the size of the market is roughly double the 3,600, another 3,700 patients that are likely or highly likely to be aPAP. And those are the patients that we'll be looking at through our aPAP ClearPath test, a no-cost antibody test that we launched recently, really to begin the diagnosis. And that's an investment and a commitment the company's made, which we've made to the community, something that we'll be looking at the long term, over the long term horizon.
But as you might imagine, based on the timeline that Matt just outlined, we are hyper-focused on the 3,600 known diagnosed patients today that we'll be looking to bring on board at launch.
And with the prevalence, how about price for us to gauge what peak sales could be?
Sure. So we've recently done some initial pricing work. And in that, we've publicly stated a price range in the $300,000-$500,000 per patient per year. In that range, we see a broad access with likely simple prior auth criteria for gaining access to MOLBREEVI. Payers, as you might imagine, are not really aware of aPAP. So when you educate them on the disease, they quickly understand the burden. They quickly understand there are no treatment alternatives. They don't view this as having a large budget impact at all. And they quickly get the clinical impact that MOLBREEVI has.
We think within that pricing corridor, and we'll, of course, do some more work as we get closer to launch. We think inside that pricing corridor, A, we have some pricing power, and B, it's going to set up for a favorable pricing environment or reimbursement environment, I should say.
Yeah, and if I could add to, Andrew. I think it was well articulated by Braden. If you think about what we're trying to solve for here, above and beyond providing the first approved chronic therapeutic for the aPAP community, which is first and foremost the most important thing. From a business perspective, with the approximately 3,600 currently diagnosed patients in the U.S., the question is, what will be the shape of the launch curve, the uptake curve, and what are you doing about it? And Braden to provide some additional details, I think it's important to note, for example, at four of the accounts that we deem to be reference centers in the U.S., you look at UCLA, Cincinnati Children's, University of Colorado, University of Florida, we're confident that there's over 100 currently diagnosed patients at those accounts.
And the intent to treat by at least two of those, what we deem to be KOLs, is that they will offer MOLBREEVI to any aPAP patient that's currently diagnosed, regardless of severity of symptomatology. And it's logical. You want to turn on the signal, right, and get the alveolus behaving in the right way to help reduce surfactant burden as early in the course of disease as possible. So the intent here is getting MOLBREEVI in the consideration set and offering for really any and all currently diagnosed patients. And as Braden had said, that's right now approximately 3,600 patients in the United States.
Great. And maybe just one question about the data. Just wanted to double check in terms of gauging the approvability of MOLBREEVI i s that my understanding is as long as DLCO hit week 24, primary endpoint, as well as you showing some kind of trend on a functional outcome, one of three key secondaries, you're good. And you got FDA buy-in around this aspect, as well as regulatory, other ex-U.S. regulatory.
Yes. Prior to the results of IMPALA- 2, we guided to our regulatory alignment around the world. U.S., FDA, EMA, as well as PMDA would be we had to have a DLCO win of stat-sig at 24 weeks. That had to happen. Given that DLCO is considered in aPAP to be a surrogate endpoint, we also had to show at least one of the key secondary endpoints had to show a numerical trend. We were thrilled that DLCO not only was stat-sig positive at 24 weeks, but it held stat-sig positive through 48 weeks. We also were thrilled that SGRQ total at 24 weeks was a stat-sig win versus placebo. SGRQ activity was nominally stat-sig positive, just based on the hierarchy piece. Then exercise tolerance test via treadmill was nominally stat-sig at 48 weeks.
So hence the reason we believe that we feel strongly that we have a real strong path to approvability around the world based on the results.
And with that data, including the durability plus clean safety plus low discontinuations, that does have commercial implications in terms of MOLBREEVI becoming a chronic therapy, durable peak sales potential. Would you agree?
Yes, I would agree.
Okay. And so now the original guidance to filing was first half 2025, but it did get pulled forward into a rolling submission starting Q4. I'll take it. What exactly prompted that specifically?
We kept the broad 1H 2025 filing because we wanted to make sure that when we did tighten down the timeline, that we would, in fact, like we have to date, hit the timeline. And a big part of this for a small company like us is that it's not just IMPALA- 2, as for example, in the clinical data set, it's also IMPALA that we'll be bringing in to be supportive. Those are important data. But it's a lot of heavy lifting. And then you just go through and we wanted to make sure that module by module, we would be able to hit the date. And we put a stake in the ground and pulled it forward and are now going to complete the submission by the end of the first quarter.
Wonderful. And in the U.S., once you complete submission Q1, would you expect an outcome?
So, given the fact that MOLBREEVI is the first therapeutic, potential therapeutic being considered by the FDA for aPAP, while we can't speculate whether there will be an outcome or not, we, as you might imagine, will be planning until we're told otherwise that there will be and be ready. So what this team won't do is take anything for granted, and we'll be ready to go. And so that's the plan. Whether or not we have one, we'll be ready to go.
Right. And then MAA submission year end 2025. And then how about other countries? Any timelines around that front?
Still to be determined. We do intend to file in Japan. We're still sorting through what the timelines look like. Again, there also comes in a small company environment, you have to make sure that you're not getting out over your skis, so to speak, with regard to overcommitting on timeline. So U.S., FDA, filing BLA is by the end of the first quarter, priority one. MAA by the end of 2025, priority two. And the rest of other geographies to be determined.
Okay. I mean, it seems like approval, it seems like a high probability as we think about risks, at least. Anything to note about the drug manufacturing side? How's progress been there? Just want to make sure everything's good to go.
Absolutely. So our primary drug substance partner is GEMA. They're based in Argentina. GEMA has been producing molgramostim for, I guess, almost 10 years. And they supplied both IMPALA and IMPALA -2. They are a CDMO, again, based in Argentina. They currently produce drug substance biologics for about 12 different products. And they have been inspected and approved by five different regulatory country authorities. They do not have a U.S. FDA approved product. They've never applied. They are heavily incentivized and motivated for this to be their first approved product. And I will note that there's also not only do we have, like we do with all of our partners, for example, in IMPALA -2, our global CRO among other partners, the Savara team managed those partners very closely. We're doing the same with all of our partners throughout the ecosystem, including GEMA.
They're also incentivized, meaning we have publicly disclosed that in our deal, they have a low single digit royalty rate on net sales over the long term. So there's real incentive structure for them to ensure that we're able to get them approved. And we're confident that we will. In parallel to that, something that we've done that we're very proud of and I think should be a best practice for like biotech companies is we are building out a fully redundant second source supply chain planning for success for a very long time. That includes over time two drug substance partners, two drug product partners, a couple of analytical lab partners. We are currently working with Fujifilm here in the U.K., actually, and on a tech transfer that we started early this year. It's on track, going very well.
The plan is, again, so that we never have supply interruption ever, after approval in the U.S., which we hope is at the end of next year. Fuji would file. We would file a prior approval supplement, a PAS. Then for the next 12 plus years, hopefully more like much longer than 12 years, we'll have two drug substance partners. Our patients around the world should never, ever have to be concerned about supply. We're confident in GEMA. We're on track to file at the end of the first quarter. We're very proud of our long-term continuity of supply strategy.
What's the latest, greatest on your appetite to pursue this alone versus working with a partner?
We've been very consistent about the following that in the United States, this is an opportunity that we absolutely can and are planning to do on our own. It's a capital efficient, operationally efficient infrastructure. We have a team that's been there and done it. For example, in the United States, you're looking at probably a field-based footprint of no more than 30-ish or so FTEs, single specialty pharmacy that will also act as provider hub services, very capital efficient and operationally efficient. In Europe, we are planning to go on our own. We're doing the work to be ready to go. We'll also be open-minded about how we go to market in Europe, I mean, to be pragmatic.
We've also said consistently that in the Asia-Pacific region, that would be something that often single asset rare disease companies should be really evaluating alternative options about how they commercialize.
Great. And I think you mentioned earlier, or you hinted at that, upon a U.S. approval, at least, there should be some kind of initial bolus. And you've even mentioned in Analyst Day or Investor Day that you should have line of sight to 1,000 aPAP patients when you're approved. I mean, by math, it's a $300 million-$500 million opportunity from the get-go. My question is, why don't you have line of sight to all 3,600? Why 1,000?
I'll give that to Braden.
Yeah. Thanks, Matt. So we've identified those 3,600 patients. And as I said, through the claims data, we have a sense for exactly where they are. And so we're beginning the work now of profiling those accounts. So as you might imagine, the 3,600 were found over about 1,000 accounts. We've prioritized those accounts based on expertise and experience treating aPAP, targeting centers of excellence, targeting interstitial lung disease clinics, and tertiary centers as well. We've brought on a couple of field-based folks early. And we have some tele-educational efforts that are going out as well as supplement those efforts. Right now, as Matt mentioned, we're doing the work to understand the optimal size for the team, as well as the timing of bringing them on.
I mention that because the experience has been in the past for many of us that you can do this with a very small team and targeted. The accounts that I mentioned, if you take the top 200-250 accounts, that gets you well above the 1,000 patient target that we've set for ourselves as the number of patients that we would like to have line of sight into to ensure a robust and rapid launch. I think there are some things here post-sizing exercise and timing exercise where we could bring on additional folks in the field and a market development type of capacity on the medical side as well that could accelerate that as well. We're obviously going to try to have line of sight into all of those patients. But we are, again, laser-focused on making sure that that launch trajectory is rapid and robust.
And so ensuring that we have line of sight into at least 1,000 of those patients early on, the early hand raisers, if you will, that might be the early adopters of it and go on therapy is our focus.
Great. And so this is part of the 3,600 diagnosed patients. Now we have this separate 3,700 likely to have aPAP that could be suitable with your antibody test that you launched in the U.S. late last year. And so when would you be prepared to share patient numbers in terms of how many patients you've gotten with the antibody test?
Sure, so I appreciate you mentioning the 3,600 because, as I've said multiple times now, that is our laser focus to ensure that we have a successful launch. The 3,700 and the aPAP ClearPath test is really an investment in the long term, and that's how we're viewing it. We're trying to be smart and efficient about how we deploy it while it's broadly available. We've done things like the ILD pilot, the ILD clinic pilot down in Florida, where we're looking at an enriched population, what we believe is an enriched population that might be more amenable to find aPAP patients through the test, so that pilot is underway. It's going to go well into next year or the first half of next year, and so we'll see as those results come out, but again, it's a small pilot.
One thing that we're doing is, as Matt mentioned in everything that we do at Savara, is we're planning for long-term success. So we're evolving the test as well in parallel, working on a dried blood spot test that would be much easier to implement point of care. And that'll enable us, and we think that'll be available in the first half of next year. That's what we're working towards. And at that point in time, I think it'll give us an opportunity to expand the pilot program to other areas across the country where we could do more broad testing and see how many of the 3,700 that we could potentially find over time.
Yeah. Just to put a finer point on the dried blood spot test, I think this is important to note that this point of care in the pulmonologist's office, the ILD clinic, four drops of blood on a card, mail it in, seven days later, you get results. I'm very proud of, again, the forward thinking that the team has had around the free diagnostic program and platform that's up and running that was launched at risk pre-data and has rapidly evolved from blood testing to dried blood spot that we'll be launching next year prior to approval, way out ahead of the game. That's how over the long term, companies that are forward thinking grow orphan rare disease markets while also staying, once again, to overuse the term, laser-focused on the 3,600 to make sure that the launch trajectory, shape of the curve maybe exceeds expectations, but we'll see.
Okay. I guess that's all the time we have there. There's always more to ask. But thanks for sharing the progress. Congrats on the execution this past year and looking forward to more. Thanks, everyone, for tuning in.
Thank you very much.