Matt Pauls and Brian Robinson.
I'm Inga.
Hi, nice to meet you.
Nice to meet you.
All right, I think we can get started. All right. All right, great. Thanks everyone for joining us here. Kicking off our second annual healthcare Innovation conference. Very pleased to be joined by the team from Savara kicking things off for us again. I'm Vamil Devan, the biopharm analyst here, Daniel Krizay from the team from Guggenheim. And with us here we have Matt Pauls, Chair and CEO of Savara, and Brian Robinson, the Head of Global Medical Affairs. Maybe Matt, it will be helpful, I think just for purposes of people maybe less familiar with the Savara story, just give an overview on how we've gotten to where you are now and then we'll talk about some of the exciting upcoming events.
Sure. Thank you, Vamil. I appreciate it. Also, on behalf of Savara, I want to thank Guggenheim for the invitation for us to participate. Appreciate it greatly. Savara is a single asset rare disease company. We have a novel inhaled biologic MOLBREEVI, which is Molgramostim Inhalation Solution. We are in the process of resubmitting the BLA, which is projected for next month, December. MOLBREEVI is being studied for, on the heels of positive phase III data from the IMPALA-2 trial, for autoimmune.
For.
Autoimmune PAP pulmonary alveolar proteinosis, a rare lung disease. It's an exciting time. We also have guided to filing the MAAs in both Europe and the U.K. in the first quarter of 2026.
Okay, great. You mentioned you touched on the resubmission coming up here, so maybe you can just talk through some of what happened over the course of the year. You had the refusal to file and now it sounds like you've made some changes around your manufacturing plan, setting up for the resubmission next month. Can you just kind of walk through what led to the refusal to file and then your decisions since then to get in position to refile?
Sure. We started the rolling submission of the BLA last December, finalized the BLA submission in March of this year, and surprisingly received a refusal to file from the FDA in May of this year related to some manufacturing CMC-related data from our drug substance manufacturer based in Argentina. Fortunately, we had been in process of doing a parallel path tech transfer to Fujifilm based in the U.K., and that was a dual sourcing long-term drug substance strategy that we had in play, and as maybe luck or good fortune would have it.
We were at a place where we were able to pivot very quickly post the again surprising RTF and approach the FDA via a Type A meeting and run past them the analytical comparability protocol that we had in place for the tech transfer and received support and alignment from the agency coming out of the Type A meeting. The strategy now is, and the alignment with the agency is to pivot to Fujifilm as the primary drug substance manufacturer, which we intend to do next month because in the resubmission of the BLA. You know, I'm very proud that the team almost, I guess approaching two years ago, started the tech transfer process to Fujifilm and we were in a position to have optionality coming out of the proverbial curveball that was thrown our way.
Okay, great. Maybe a couple more questions on the regulatory side, then we'll switch to the commercial.
Sure.
One question we commonly get is around your IMPALA-2 trial and maybe one you can just summarize the sort of key findings that you had from that trial. I think the question to get is sort of what you've agreed with the FDA on in terms of what you needed to show for the primary and the secondary endpoints to get a point where you're comfortable filing and getting approvals. Maybe you can sort of walk through some of those prior conversations and then the data itself and what you delivered.
Yeah, sure, no problem. I mean, in autoimmune PAP there is nothing approved in the United States or in Europe or the U.K. MOLBREEVI is really the first and only application ever in this orphan rare disease aPAP. With breakthrough designation, clearly the unmet need is significant. With regard to IMPALA-2, primary endpoint is DLco. I'll have Dr. Robinson talk through the trial design and the results. It's really the totality of the evidence.
Objectively, by showing that MOLBREEVI performed better than placebo at the primary endpoint of 24 weeks and the durability of effect was seen through 48 weeks combined with the key secondary endpoints of SGRQ, total activity, and exercise capacity via treadmill test, we believe that the whole picture, the totality of the evidence, is supportive of a path to approvability both in the United States as well as in Europe and also the U.K. As a reminder, there is also the support of data from the first phase 2/3 trial IMPALA, which was technically a failed trial based on four outlier patients who, you know, unfortunately skewed the results and so again led to a non-statistical significance result.
Those supportive data and the breadth of the data we believe, you know, again combined with the win on IMPALA-2 primary endpoint as well as some of the key secondary endpoints puts us in a good position around path of approvability in the U.S., U.K., and Europe. Brian, do you want to just quickly touch on the results from IMPALA-2?
Yeah, sure. Matt gave a really nice outline of the overall IMPALA-2 study. Just very briefly, this is a global study where we enrolled 164 patients in 43 centers across 16 countries. The primary endpoint was the change from baseline in DLco, which stands for the diffusing capacity of the lungs for carbon monoxide. Really, this is just a surrogate measure of gas transfer. We use carbon monoxide instead of oxygen because it binds more tightly to hemoglobin. That is how this study was done. That was the primary endpoint, and as Matt said, the double-blind period was a 48-week double-blind period. The primary endpoint was at 24 weeks of the change in DLco from baseline. We met statistical significance there.
As Matt also said, at 48 weeks the durability was still there from the change from baseline, which was also statistically significant. That was the primary endpoint and one of the key secondary endpoints. A couple of the other endpoints included SGRQ, which stands for the St. George's Respiratory Questionnaire, which is a respiratory quality of life pro that was statistically significant at 24 weeks and was numerically significant at 48 weeks. That breaks down into two different modules. One is the total score and then the activity score. Lastly, there was exercise capacity, which Matt also mentioned, which was measured using a treadmill test, which is unique in a pulmonary diseases. This is the first study that used that as an endpoint to study patient functionality.
That was also found to be numerically significant at both 24 weeks and at 48 weeks.
Vamil I'll also mention that of the 164 patients that enrolled in the 48 week double blind placebo controlled IMPALA-2 trial, 159 of the 164 completed and 159 of the 159, so 100% of the patients roll over into the open label extension, which I think is rather remarkable.
Okay, maybe we'll switch to more of the commercial side and then a couple more and I'll turn to Daniel. Just the market here. You mentioned there's no approved treatment options for these patients. Maybe, I don't know, either you could just talk to how are they currently managed, this sort of whole lung lavage process or the procedure that they could go through, how does that sort of fit in? If you can talk about kind of your go to market strategy, how you sort of make an impact and show the value to providers and patients.
Will you take the first part and I'll take.
Yeah, sure. To your point, Vamil, the only really recognized management strategy for this disease is a procedure called a whole- lung lavage, which sounds exactly like what it is. It's basically a washing of the lungs and it's a pretty harrowing procedure. It really is just, quite frankly, a plumbing or a mechanical removal of the buildup of surfactant. It doesn't address the underlying cause of the disease. Because of that, it frequently needs to be repeated. As you can imagine, this is a completely barbaric kind of procedure. Just taking a step back, Molgramostim or MOLBREEVI does address the underlying pathophysiology of the disease, where it goes to where the defect is, which is the problem with signaling with GM-CSF. As I mentioned, whole lung lavage does not do that.
What's interesting about that, looking at these two approaches to managing this disease, is that with the publication of the IMPALA-2 data and a recent review article that just came out last week that looked at the treatment strategies for autoimmune PAP, both of these pieces of data suggest that GM-CSF really should be the gold standard in terms of managing this disease. A whole lung lavage should be set aside as a rescue therapy or for patients who are end stage or who are refractory to other kinds of treatment.
Okay, let me turn to Daniel then. Maybe want to dive a little deeper on the commercial?
Yeah, yeah, sure. Thanks, Vamil. So you guys recently announced an updated U.S. claims analysis. We identified additional aPAP patients. So broadly, like how did this analysis compare to your previously published analysis? And what gives you confidence that this analysis is a more accurate representation of the U.S. population?
Yeah, thanks, Daniel. A couple of years ago we did U.S. claims database analysis work and based on patients with a known identified code for PAP, we identified for autoimmune PAP, which is about 90% of PAP, and it is well accepted that 90% of PAP diagnoses are autoimmune. We noted that there were in the United States 3,600 or so patients that were identified. We decided to redo the analysis and we used a bigger, broader, arguably better data source that had approximately 300 million lives or so in the United States. It, unlike or differentiated from the previous work, had three or four times greater number of records. Again, broader, deeper, and we believe more accurate, and combined with the fact that we, Savara, have been investing over the past few years in disease state awareness in diagnostic testing.
Of course we have the EAP up and running. We weren't surprised when we rerun these analyses after torturing the data and ensuring that we put it through multiple filters before we announced it publicly. We weren't surprised that the market actually is now bigger than it was a few years ago. We were a little surprised it was about 50% bigger. We are now highly confident based on these analyses that there's about 5,500 or so patients identified with autoimmune PAP in the United States in contrast to, you know, just a short couple of years ago, which was 3,600. Not surprising, you know, in many respects. Again, because when you're a first mover in an orphan rare disease category that just hasn't had investment and attention and focus, you know, we're seeing the market come together and we're working hard to structure it.
Okay, great. Can you maybe talk a little bit about how disperse are the physicians that are managing these patients? I know on the initial analysis you guys had around 1,100 or so centers where these patients are located. Is this still the case or any changes there with this new analysis?
It is still the case. Approximately. Let me take this from a different angle. When we think about the go to market strategy and what, you know, the deployment of resources, we believe that a customer facing group of 25-30 in that range will allow us to be able to, you know, address a majority of the 5,500 patients or so. I would not call it hyper concentrated, but I also think it is kind of down the middle of the fairway, so to speak, from, you know, having to chase down kind of onesie twosie versus, you know, hyper concentrated. We actually think the way it is coming together is rather efficient. The commercial model between that and single specialty pharmacy that also will have, you know, patient hub services, white glove service, etc.
We think it's both capital as well as labor efficient to be able to have really what we believe to be, you know, it's going to be great commercial success.
Okay, great. Maybe moving over to the ex U.S. side of things, can you maybe provide your updated thoughts on the ex U.S. commercial strategy? Do you believe going it alone makes the most sense here? Are you looking for commercial partners in some or all of these geographies?
Prior to the financing transactions that we executed a couple of weeks ago, you know, we felt strongly that we would, we should do the commercial preparation and to go it alone in both Europe and the U.K. Now on this side of the transactions, we surely believe that especially given the fact not only is the commercial opportunity in Europe, it's real, it's analogous, very analogous to the United States opportunity with regard to diagnosed prevalence numbers. Given some of the kind of policy overhang issues that are still unclear related to MFN tariff, et cetera, we believe it's even more important for us to prepare to go it alone.
However, we have been very clear that over time while we have no pressure, we feel no pressure to have to monetize any parts of the globe, we get to hold on to the full value of MOLBREEVI. We will be open minded and pragmatic with what we believe to be the right strategy over time. As of today the plan is to go it alone and we are in the process of that. Commercial preparation, organizational preparation in again, both EU and U.K. Asia Pacific is a different story. We think that that's pretty consistently a tough math equation for a single asset rare disease company to make work. Especially given the policy- related issues that I mentioned.
Maybe I'll jump a couple other things. You touched on the recent financing and we've got a couple questions on that. I just want to touch on this. Just the decision to do the kind of the two step financing, the decision to do that, the decision to do it now sort of right ahead of the submission. Maybe you can just talk through sort of the thinking there. Now that you have these proceeds, how do you think about your sort of cash need and runway going forward?
Yeah, so why now is question one and it purely opportunistic. We were approached about, you know, royalty financing opportunity we were in. We, you know, we did robust market check with regard to royalty financing and it was clear that that two step, two part, two bit strategy made a lot of sense. Purely opportunistic and I've been doing this a long time. One thing that I have definitely learned is that trying to time the market with regard to capitalization strategy is often not a good strategy. That's purely it. Whether it would have been pre resubmission or post or this was the right strategy. When it comes together nicely, which it did, both the follow on equity raise as well as the royalty piece, you run with it and you make it work.
We think it was the smart, prudent thing to do and it will prove out over time. With regard to Runway, this very clearly put us on a path with regard to, you know, Runway, that while we're not putting a stake in the ground about getting to, you know, anything like cash flow positive or profitability, let's just say that this puts us on a path where we are laser focused on execution and feel like we are going to be able to invest earlier, better, broader to ensure that we exceed expectations.
Maybe the last couple questions here in the time we have left, one is this market build and the analysis you've done, you also have this autoantibody test that's out there. I think the question we get a lot from investors again is how big is this market and wanting to see more granularity. How are you thinking about between now and sort of the time you're launching, at least for the street purposes, kind of highlighting the progress you're making in terms of identifying patients or maybe expanding the market with your testing that's now out there? I think it'd be helpful. I think people just kind of curious on that. I think that's probably the biggest question we get on the story. I think the data's there, the opportunity is there. I think they're just curious on the commercial.
Yeah, sure. We feel like again, in the way the story is coming together, that in the thesis, quite frankly, is that we have an opportunity here to, through our no cost antibody testing program and the dry blood spot test, which you know, is often running and being utilized. At the right time, it may make sense to come back to the market and talk in more granularity with regard to testing numbers. The minute we go down that path, then of course that's front and center. You know, it's never enough, quite frankly. You know, it's something that we believe at the right time could be really valuable, powerful information. Suffice it to say the antibody testing, the dry blood spot test is being utilized. It absolutely is being utilized here in the United States.
We also remind you we have an EAP up and running. And we're not talking those numbers at this time specifically, but it's being utilized. At the right time, we believe that it could be very valuable to the market to share more granular details. We're not going down that path right now. Let's just say that with 5,500 patients, IMPALA-2 published in the New England Journal of Medicine, alignment with the agency coming out of the Type A meeting, you know, we've made great progress over the last four or five months. The market opportunity is real, the unmet need is significant, and we are very well capitalized.
Okay, and maybe just to lay out the path forward here then. You mentioned refiling in December. Presumably that means we hear about an acceptance a couple months later.
Yes.
Instead of an action date, sort of middle part of next year, August or so.
Assuming that priority review is granted at or around filing, that would put us at a PDUFA of August-ish or so of next year, and we'll be ready to go.
Okay. Looking forward to following the progress. Maybe next year, this time you'll be a commercial stage company.
Yes.
Okay, great.
Thanks very much.
Thanks so much. Thank you.
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