Hi, everyone. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies. Thanks for joining in. It's my pleasure to have the Savara team with me today. To the direct right of me is Matt Pauls, Chairman and CEO. To his right is Braden Parker, Chief Commercial Officer, I believe. Welcome, both of you.
Thank you, Andrew.
Maybe to start, talk a little bit about Savara, what you're trying to achieve, what your program is, and then milestones over the next 12 months would be helpful.
Yeah. First of all, thanks, Andrew, and to the Jefferies team for the invitation to participate. Savara is a single-asset rare disease company focused squarely in the orphaned rare pulmonary respiratory space. The single asset is Molrivi, which is molgramostim inhalation solution. We have, in the summer of 2024, reported positive phase three data for the treatment of autoimmune PAP or autoimmune pulmonary alveolar proteinosis, a rare lung disease. We are in the process of tidying up the BLA for submission next month and have guided to submitting MAAs in both the E.U. and U.K. in the first quarter. In addition, we are just on the other side of a recent kind of dual-pronged financing strategy, so very well financed, pro forma currently about $264 million on the balance sheet. An exciting time to address what we believe to be a significant underappreciated unmet need in the aPAP population, both in the United States as well as Europe and the U.K. In the proverbial homestretch, so to speak, with fingers crossed, U.S. launch in probably the August or September timeframe next year.
Thanks. As we think about the aPAP market, maybe talk to us what you think the peak sales opportunity for Molgramostim inhalation solution could be. How many patients in the U.S.? Why are you so confident in that number? What could be the price?
Sure. While we won't get into guidance related to peak sales, we will provide a sketch here for consideration. Let me tackle, first of all, the EPI literature and the current corridor there, and then I'll turn it over to Braden to talk in more detail about pricing as well as market size. In the EPI literature, the current range around diagnosed prevalence at the low end is approximately six or seven per one million. The current literature high end is about 26 per one million. That's relevant because it fits very nicely into what our current estimate is based on claims database work in the United States. Braden.
Yeah, as Matt mentioned, there's quite a range in the published literature for the epidemiology of this disease. We wanted to put a finer point on that by doing a US claims data analysis. We had done one a few years ago, and we thought it was time to refresh that. Using a different data set this time, a much larger, more comprehensive data set, we embarked on this analysis. That data set has both open and closed source data, which results in roughly 100 billion records that we went through. We're very fortunate in the autoimmune PAP market that there is a specific ICD-10 code for PAP. Autoimmune PAP is 90% plus of it. It's a very good marker for the size of the overall US market. When we did this analysis, we uncovered over 6,100 patients with a PAP diagnosis.
Taking the 10% haircut for autoimmune PAP, you come up with roughly 5,500 patients in the U.S., which, as Matt mentioned, would put you in the 15-16 patients per million range or kind of right down the middle of the epidemiology. We have a very high degree of confidence in these data because we did try to reduce the risk that often people see with claims data. First of all, all patients were tokenized to ensure that they're unique and there was no double counting. They had to be active in the system from January of 2023 through the first half of this year. We know they're alive and active because they've had claims in the system during that time period.
To make sure that there was no misdiagnosis or miscoding, they had to have either multiple codes in the system or a code and markers of autoimmune PAP, whether that's symptomatology or visits to pulmonology or referrals from pulmonology, which would be consistent with the disease as well. For all of those reasons, we have a high degree of confidence that 5,500 is the floor in this market. Because of the range that Matt mentioned, we think there is upside there. In terms of price, I think that was the other part of your question. Sorry, Andrew.
No problem.
We have done previous payer research as well. Not surprisingly, in rare disease, payers are not very familiar with many of these rare diseases. Autoimmune PAP is no different. When you educate them on the disease, they understand the burden of illness. When you educate them on the clinical data for Molrivi, they are impressed with it. We identified a pricing corridor between $300,000-$500,000 per patient per year, which we have since narrowed to $400,000-$500,000 per patient per year because we do think there is pricing power in this market with the strength of the clinical data now being published in the New England Journal of Medicine. Within that pricing corridor, we expect full coverage of the drug with typical prior auth criteria to access.
Great. With 5,500 diagnosed US patients, you're very confident in that number. You used to provide numbers on undiagnosed patients. What do you think that number is?
We did not this go around with our claims database analysis do any kind of machine learning or AI against it. I think it's safe to say on a couple of fronts, we think that 5,500 is the floor because, first, there was no projection on the rest of the U.S. population. This claims data set represents about 300 million lives. The most recent U.S. census data, I think, has the U.S. population at about 340 million. You could potentially get a few hundred more on top of the 5,500. Importantly, because of the range that Matt mentioned in the literature, we think there is significant upside as well.
Yeah. I think to add to that, you know, when you look at the EPI literature and if you were to convert the 25 or 26 per one million, you know, clearly the 5,500 gets you much more up into the 9 or 10,000 range. I'll also add that given the fact that there has never been a chronic therapeutic approved in the United States, E.U., or U.K. for aPAP, and if you think about the hallmark cardinal symptoms of the disease, chronic cough, progressive breathlessness that gets worse over time, lung infection, those are pretty nonspecific. We think, in fact, that there are many, many patients undiagnosed that are, for example, being seen in the ILD clinic setting and are in need of attention and potential diagnostic testing.
Okay. Maybe one last question around the overall big picture. Compliance discontinuation rates, those do affect peak sales assumptions. What are your expectations around those two variables?
Yeah. In IMPALA-2, which was a 48-week placebo-controlled trial, 164 patients were enrolled. 159 completed the 48-week placebo-controlled trial. Of the 159 who completed it, all 159 roll over into the open label extension. I think you take that and then you look at the safety and tolerability profile and data based on the IMPALA-2 trial. It's clear that there is not a safety signal and that Molrivi is well tolerated. That's all very important for obvious reasons, mainly because this is a disease of auto, it's autoimmune. It's probably lifelong for most patients. Most patients who are diagnosed and treated with Molrivi probably will need the therapy for most of their lives.
I'll just add, Andrew, that there are a couple of other factors that we think will play well into strong compliance and adherence. Most notably, the nebulizer itself. First of all, Molrivi is once daily, which is very convenient. The nebulizer itself is very easy to use. The nebulization time is only three to five minutes per day. When you add in setup to clean up, maybe 20 minutes a day as well. Those factors combined with all the things that Matt had mentioned, including the safety tolerability profile, we think sets up well for strong adherence and compliance.
Thank you. In the meantime, you're on track to resubmit the BLA in December. That would imply potential FDA acceptance in February of next year. Why are you confident you will not get an RTF this time?
Yeah. The RTF issue, the reason for the RTF was one distinct reason, and that was based on some manufacturing-related control data intra-batch production at our longtime drug substance partner in Argentina. In parallel, over the last 22 months, we've started a tech transfer to Fujifilm based in the U.K. On the heels of the RTF, we were able to approach the agency and gain alignment to pivot through our analytical comparability protocol that was in place through the tech transfer at Fujifilm. We're confident that we were able to navigate through the RTF issue because by making the move to Fujifilm, we address the single RTF issue because they do the sampling and the data are already available. We are in the process right now of gathering the analytical comparability data and are right on track for submission in December and have great confidence that it will be filed and our base case is priority review. You are correct. That would put us in the pursuit, like I mentioned earlier, about August or September of next year.
Thanks. Let's just say it did get accepted. I feel like the work my team has done is CRLs 50% of the time are due to CMC manufacturing. Can you reassure us that would not be an issue?
We are confident that the CMC strategy via Fujifilm is rock solid. I think it's important to note that for all companies, any and all companies that are in the regulatory process, that until your drug is approved, it's not approved. Just keep driving hard and pushing forward. We have great confidence that we're going to be able to get Molrivi in the hands of physicians in the United States next year.
Okay. How do you envision the front page label to say, is it simply for aPAP patients or is there some kind of narrower indication, for instance?
Yeah. While we can't speculate on what the ultimate label would be, I think it's fair to assume that for patients with a diagnosis of aPAP, they will be eligible for therapy. Most of this really comes down to payer adjudication. Braden, you want to comment on payer adjudication?
Yeah. I mean, I think that, again, the payer audience is unfamiliar. When you do educate them, they can see the clinical benefit as well. What we've heard time and again from payers is really that they will default to the treating physician as to who's qualified or not qualified to get therapy. We have a great degree of confidence that to the extent that you can have a good reimbursement environment, we should be in that area.
Okay. Great. Maybe let's shift to market preparedness. Good luck on the re-filing and resubmission and so forth. To level set things, it seems like you, congratulations on getting more cash. Has your strategy around launching US, ex-US changed? Do you think you can do these launches yourselves?
Let me tackle ex-U.S., Europe and U.K. first. We'll file the MAAs in both Europe and U.K. in the first quarter. The plan, the base case, is to go it alone for a few reasons. One is the market opportunity in Europe and U.K. is real. It's also a, relatively speaking, well-constructed market. We know the reference centers. We know the key physicians and KOLs. We know where the patients are being diagnosed and treated. It's a real opportunity, one. Two, strategically, given some of the current ongoing policy-related issues that we and others are trying to navigate regarding MFN and tariffs, it makes a lot of sense for us to continue to plan to go it alone and maintain full control over Molrivi. I think third of all, we can do it. We can do it in a capital labor-efficient manner and maintain full value and control. Finally, we have the balance sheet to support it. That is the base case in ex-U.S. In the U.S., I'll defer to Braden to talk about market preparedness.
Yeah. I think we're in a great position, given the recent funding, to go deeper in our investments, bring on the market development team early, which will eventually become the sales team. We already have the leadership of that team on board and some regional directors who are out there knocking on doors and profiling accounts already. This gives us the opportunity to bring on the rest of the team and perhaps a fuller team than originally discussed. We're looking at approximately 30 customer-facing folks, maybe with a few reimbursement folks thrown in there as well. This gives us the opportunity again to do a lot of the work. Typically, with these rare disease launches, you would hire the field force contingent upon approval, and then they're going out trying to learn their accounts and profile their accounts.
Here, we're going to be well ahead of that game since they'll be on board early, which gives us an opportunity to really hopefully exceed expectations at launch by doing that work early. We've got an awareness campaign that's been out now for a couple of years, both on the physician side and now on the patient side as well. Of course, we have the testing program out there as well, which is our long-term commitment to the aPAP community.
Thank you. Speaking of expectations, you've been adamant to the street that you'll have line of sight to 1,000 patients when you launch. I mean, literally, was it last month or this month you're at 900? Isn't there going to be—how do we reconcile that you're going to find 100 more in the next eight months?
Yes. Let me be clear. We will clearly exceed expectations on the line of sight number. The number was originally created with our original timeline for the approval. We never decided to change that. When the timelines changed, just because we wanted to continue to aggressively make sure that we're profiling the market as much as possible. That number will change. We'll have significantly more by the time of approval. Keep in mind, even with the 1,000 number, that is well more than what we need in the early part of this launch to have an incredibly successful launch. We are very confident that we'll continue to profile and confirm patients leading up to and exceeding probably the 5,500 at some point.
Thanks. Within the line of sight, the number of patients you found, what proportion of those are coming from the ICD-10 codes you are mentioning versus the blood tests that you have diagnosing the undiagnosed patients, I guess? Maybe even your EAP program. Is there a breakdown you can provide?
Yeah. On both EAP as well as the no-cost dry blood spot antibody testing program that we have propped up and has been up and running now for a couple of years. We're not talking specific numbers just because it's one of those situations that it's never really enough once you start going down that path. Suffice it to say that there is demand for the EAP program, and there is utilization of the dry blood spot tests in the US, and it's growing. We look forward to, at the right time, sharing more detail there. Let me take the first part of the question, take it from kind of a different direction. I think one of the things that you, the question we get often is who will be eligible for therapy upon approval, mild, moderate, severe, and how do we think about that?
How we think about it is reflective of what we've heard from physicians. That is, if a patient is diagnosed with autoimmune PAP, regardless of symptomatology, they should be offered Molrivi. It makes a lot of sense. Even mildly affected patients should be considered for therapy. This is an autoimmune disease. It's not going away, probably not going away. This is all about reducing surfactant burden as quickly as you can and for as long as you can. The earlier that patients start on therapy, the better. Remember, when patients become very severe, they often will have to go into the hospital for a lung lavage, a barbaric rescue procedure, which is effectively the power washing of one's lungs.
Now, while we can't right now assert that Molrivi will prevent that, what is logical is that the earlier you start to reduce surfactant burden, the better, especially with a therapy like Molrivi, and again, based on safety and tolerability data from the IMPALA-2 trial, that you have an opportunity to intervene in the disease much earlier. We know for sure patients want to do everything they can to avoid a lung lavage.
Thanks for clarifying. Yep. Again, one more time, line of sight well over 1,000 upon launch. On a $400,000, let's just say net price, that's $400 million. You're saying in the first year, all of them should be on the drug?
We are not saying that. We want to be very, very careful to set appropriate expectations. I think the way to think about it is, Andrew, the line of sight work that the team are doing is kind of old-school orphan rare disease market prep. It's confirming, identifying, building relationships, getting the market ready for an approved therapeutic like Molrivi. Now, how many patients start on therapy at launch? What's the bolus? What's the shape of the curve? This is, for us now, especially on the other side of the financing, an opportunity for the market to speculate on what they believe that to be. We are just going to continue to tell our story and what we believe to be the potential for solving a real unmet need for the aPAP community and ecosystem. We are not signing up for that, but stay tuned.
All right. Very good. In terms of IP patent protection, as we think about the tail value, last question, Molrivi, can you walk us through that?
Yeah. Thank you for that question. Molrivi is an inhaled biologic, so large molecule in a nebulized delivered via nebulization. In the United States, based on BLA approval, assuming that, would afford 12 years of regulatory exclusivity. In Europe, U.K., with orphan drug designation, it would be 10 years. However, what's important to note, beyond that we have a couple of patents. We have a joint patent drug device combo that's being prosecuted globally in partnership with Pari, our partner, and also a formulation patent that's being prosecuted. Setting those aside, we also have the nebulizer's proprietary agreement and nebulizer that we have a long-term agreement with Pari, our nebulizer partner. We have the nebulizer locked up. We have 12 years of regulatory exclusivity in the U.S., 10 in Europe.
Beyond that, probably is going to be pretty difficult for anyone to ever develop a biosimilar for a nebulized inhaled large molecule biologic. We think the terminal value on this is significant and the revenue potentially way beyond the 12 years in the U.S., for example.
Yeah. Me too. Okay. That is all the time we have. Thank you so much for the updates. Best of luck. Thanks again for listening.
Thank you.