We're gonna get started with the next session. I'm Andrew Tsai, Senior Biotech Analyst at Jeffries. Thanks for joining us. And it's my pleasure to have the Savara team with me. To my direct left is Braden Parker, Chief Commercial Officer. And to his left is Matt Paul's Chairman and CEO. And to Matt's left, Brian Robinson, EVP of Medical Affairs, is that correct? Okay, well, thank you for joining me today, team. So there are some people who may be less familiar it with the Savara story so can you just give us an introduction about the the company um talk about morbidity where you are at milestones over the next 12 months and then we can go from there
yes thank you Andrew and thanks to Jeffries for the invitation to participate we appreciate it I'm Matt Paul's chair and CEO of Sivara. Sivara is a orphan rare disease company, single asset, Mulbrevi, which is a novel inhaled biologic for being currently under review at the FDA for a rare lung disease called autoimmune PAP. So, it's autoimmune pulmonary LVLR proteinosis, and we will refer to it as APAP for the remainder of the presentation. It is an autoimmune disease, lifelong chronic disease that Dr. Robinson will talk in more detail about, but suffice it to say that it is a disease at a very basic level of surfactant burden and surfactant buildup in the lungs, which causes pretty significant issues related to breathing quality of life, and given the fact that it is autoimmune, that it is more often than not a lifelong disease. Currently in the United States and in Europe and the UK, there is no therapeutic approved. There is a rescue procedure of arguably last resort called whole lung lavage. And when patients, their dyspnea and, you know, breathing and quality of life get significantly bad, if they're able to find a physician and an institution that would be willing to effectively power wash their lungs to mechanically remove the surfactant for arguably, again, and short-term relief, then they may elect to undergo that. But that is that procedure, that rescue procedure, holomophage, is surely not the answer to the kind of, you know, a chronic therapeutic approach to addressing autoimmune PAP. Most recently, we reported that we had $203 million on the balance sheet. And in parallel to that, we've also, from a cap stack, you know, cap structure and capitalization strategy perspective, have, upon FDA approval, a royalty agreement with RTW that would be a $75 million capital infusion. And we've also, in parallel, arranged a $75 million debt facility at our discretion with Hercules. So up to $150 million in non-dilutive financing upon FDA approval. PDUFA date is November 22nd, so we're within the six-month window. And we have a high level of confidence and conviction in path to approval in November. So it's a very exciting time.
Great. Thank you. And so maybe to start framing the market opportunity for this indication, remind us the total addressable market, how many patients are there in the U.S. alone, and why are you convinced in that number?
Yeah, thanks for the question, Andrew. So when you look at the literature, the epidemiology and the literature, you get a wide range from six patients per million all the way up to 26 patients per million. We obviously wanted to put a finer point on that, so we've done over the years some claims database work, and most recently leveraging the VIVA database, which represents over 300 million lives, over 100 billion records with open and closed source data. We're fortunate in that there is a specific ICD-10 code for PAP. Autoimmune PAP represents 90% plus of all PAPs. So when you look through that data set, we identified 6,100 patients with a PAP code. So about 5,500 patients when you take the 10% haircut that have autoimmune PAP in the U.S. And we feel very confident in that number for a number of reasons. First, every patient was tokenized within the data set, so we know there's no duplication. Secondly, they had to be active in the system within a recent period of time. so some type of claim had to come in so we know that they're alive and then finally to reduce any kind of miscoding error we had a number of clinical criteria that we applied to the data set as well leveraging a third-party company and that gives us great confidence in the 5,500 now in the context of the published literature that would represent about 16 patients per million so right in the middle of that range that I noted earlier so that we believe is the floor now in the US market and we'll see how high it goes
from there. Great and then I ask you every time too on price just to make sure nothing's been changed but what are you thinking about the pricing bookends
on a net basis? Yeah so we've I appreciate the question every time and I will give you a similar answer which is we've identified a pricing range of four hundred to five hundred thousand per patient per year for this product and And within that range, we have a high degree of confidence of coverage and coverage to typical prior auth criteria, no real concern about budget impact from payers. So we feel that that is a nice sweet spot for this product to extract value, but also to gain access for patients.
And just to double down on the ultimate use case of this product in the, you know, people People can understand if a patient's moderate or severe with APAP, the question is mild. Why would this be used in mild patients as well if it was approved?
So I'll take that and ask my colleagues to opine as well. So I think, you know, what we've heard from physicians and most importantly from autoimmune patients is that, you know, if a patient is symptomatic enough to have been or are currently diagnosed with autoimmune PAP, they are, even if deemed mild, you know, from a symptomatology perspective, they're impaired enough that they went on the journey to figure out what was going on. And this is a disease that clearly can, you know, can kind of wax and wane. But what doesn't change is when you're diagnosed with autoimmune pap, you're diagnosed with autoimmune pap. So let's talk about the patients that maybe at this moment in time have milder symptoms, right? Maybe their dyspnea has stabilized, it's still impaired, but it's not getting worse for a short period of time you know what what again feedback we've gotten from patients as well as physicians is what they're very keen to do is to try to do everything they can to prevent patients from going from mild to moderate right patients any patient that has had gotten worse you know bad enough to have a whole lung lavage never wants to have another whole lung lavage so i think the way to think about this is that if you can if you can get to patients as early in the course of disease as possible and hold them there right that is a great thing so that's why again the feedback from physicians and from patients is that even if deemed mild they want and should be considered for starting on Mul Brevi as soon and as early as possible.
Makes a lot of sense. Yeah, and so maybe talk about the ultimate compliance discontinuation rate of this product. What, for instance, what did you see in the phase three studies on those rates? But you also just shared open label extension data, ATS, a couple weeks ago or so. So maybe talk about how you're thinking about those rates because that can affect sales each year absolutely
so let me give a little framework and then I'll turn it over to dr. Robinson so when we launched Impala to first patient in was in June of 2021 so we launched a rare lung disease global phase three trial right in the midst of COVID and daring man you know and or maybe fortunately it worked out really well but at the time it was a little nerve-wracking. We fully enrolled it on time, actually over-enrolled it on time during the pandemic. We targeted 160. We enrolled 164, a 48-week double-blind placebo-controlled trial. So in the midst of the pandemic, we over-enrolled this rare lung disease trial where patients raised their hand and wanted to be included in a 48-week double-blind placebo-controlled trial where they had a 50-50 chance of getting nothing for a year, right, with the hopes that at the end of that they would be able to get, you know, Mulbrevy in the open-label Of the 164, 159 completed the 48-week portion of the trial. and all 159 or 100% of those patients rolled over into the open-label extension. Brian, do you want to talk about the open-label extension?
Yeah, sure, Matt. But I just want to go back to one question that you had, Andrew, regarding mild patients. One of the things that's important to consider is that, by nature, autoimmune PAP puts patients in an immune-compromised setting. And because of that, patients are susceptible to opportunistic infections. So this is yet another reason that's important to treat mild patients. I just think that's an important point to be made. But to answer the question about the open-label extension, as Matt said, 159 patients went into the open-label extension period. And we just reported at ATS last month the first 48 weeks of the open-label extension where those 159 patients entered that phase of the study. And in that study, there were nine patients that dropped out of the study. It's important to note that these nine patients dropped out not because of treatment-related adverse events or lack of tolerability. There were a variety of reasons why patients dropped out, including patients moving and things of that nature. So the retention rate is significant. And it's, you know, I think it's because patients feel better and do better and are able to breathe. So that's a key part of what happened, what we've seen in the first 48 weeks of the OLE.
That's great. So that's two years for some of these patients. That's right. Okay, very good. And so now the application is being reviewed by the FDA. You recently got an extension from the FDA fairly early on post-acceptance. So what exactly happened here, and why should we feel that your application is okay and will be approved ultimately?
So it was a very general correspondence from the agency, just stating that they were giving us a three-month PDUFA extension. Unrelated to, you know, there was no comment around safety, efficacy, or manufacturing at all. So just very generalized direction. And that was it.
Wow. So the positioning is, it sounds like it's an FDA bandwidth situation. It's not something related to, I mean, if it's not safety, efficacy, CMC, what else could it be, was my line of question.
No, fair question. And I don't know. All I know is that there was no mention of safety, efficacy, nor manufacturing, one. And I can't nor I shouldn't speculate on, you know, bandwidth, et cetera, with the agency. You know, I do think when you look at precedent analysis that over the last, you know, few years, especially with applications that have priority review, the six-month review versus a standard 10-month review, Um, you know, it, it, it, it hasn't been uncommon for there to be, um, uh, you know, a three month, uh, PDUFA extension.
Okay. Uh, no problem. If you don't want to answer it, I do get asked. So I'm just very curious. Absolutely. There's a, you know, it was triggered by an information request by the FDA. What was exactly that request that triggered this whole ordeal?
So there wasn't anything named specifically that was the reason for the three-month extension. It really was just a very general communication that said we're going to need more time to review the application. And so, therefore, we're extending your PDUFA date by three months. That was it.
Thanks. You're welcome. And then at the same time, though, as it's being reviewed, we're not necessarily out of the woods just yet, even though the precedents would support approval. Like, if the FDA wanted to reject it, I think they could have waited for the original PDUFA and issue a CRL for it. I don't know. But anyway, you know, CMC side of things, sure, you got it. You know, the original, there's an RTF originally with the first supplier, but you've essentially resolved it, but at the same time, there is still going to be inspections with the second supplier. So how should we feel or why should we feel confident that CNC inspections will be okay for this review?
Yeah, I think the way to think about this is, you know, look again at the journey over the last year And, you know, coming out of the RTF, getting alignment with the agency around the analytical comparability protocol was step one, and we did. Two was then produce the data to support the analytical comparability protocol with, you know, Fujifilm, which we did. That then supported the BLA resubmission. because but for that, we wouldn't or couldn't have, you know, resubmitted the VLA. So we did, and it was accepted. And so it's under active review. I think, you know, as a reminder on this tech transfer process, you know, this is a, while it's a biologic, It's a pretty elementary, kind of basic biologic and tech transfer process, non-glycosylated. It's the same capacity, so it's not a scale-up. It's really just taking the same process and same capacity and moving it to Fuji. They're a world-renowned partner, and they have a lot of experience in, you know, tech transfer and, you know, and we're at the biologic center of excellence for them in the UK. So we have a high level of, again, confidence that we have a path to approval in November across the application, you know, the BLA that we submitted.
Yep. And then at the time of the acceptance earlier this year, did the FDA happen to confirm no adcom is needed explicitly?
Yes. So they did, and we disclosed that previously, that they did express that there was at that time no plans for an advisory committee, and that was when they accepted and filed the BLA.
Great. And come November, let's just say it is approved, which I think will be the case, what are you hoping the front page label to read specifically? The front page label claim is it for APAP full stop? Nothing, not a skinny label by any means. Is that the expectation?
We anticipate that it will be for the treatment of autoimmune PAP.
Yeah. And then on, I mean, as I think about the precautions, safety section, I mean, is there really much to mention on that side of things, too?
Fortunately for us, and most importantly for patients and physicians, is that if, you know, with the large body of data now, So based on Impala 2, which is the largest autoimmune PAP trial in the history of autoimmune PAP. And then the supportive trial, the Impala trial, the, you know, really proof of concept phase 2-3 trial. If you look, there's no safety signal, and tolerability is remarkably good. And I think that is evidenced by, you know, the retention rates of patients staying, you know, on drug and in both trials.
And let's just say, again, you're approved in November. When are you prepared to launch specifically?
Yeah. So if you think about timing, you know, the end of November, you're into the end of the year, holiday period, et cetera. we're really orienting everyone around drug being in the channel and kind of getting the engine turned on in the first quarter and then like every other orphan rare disease launch especially a first mover like Mulbrevy in autoimmune pap you know that first quarter you're you're you're adjudicating you know patient start forms you know prescriptions you're working you know really on a manual basis of getting patients you know through through the you know payer and reimbursement process and then you you know the goal here is you launch and you know the beginning of the first quarter and then you know the
second quarter you hit with great momentum yeah and so you used to share a nice data point on how many patients are ready to go you call the direct line of sight and those a thousand as of December and you've mentioned that it would be significantly higher by the time you're approved so if I did a thousand on a 400,000 net price that's already 400 million in year one understood that, you know, Q1, you know, you're adjudicating, but should this be a bolus in Q2,
Q3, Q4? Yes, I'll have Braden comment, but let me set this up a little bit. I think the way to think about, so line of sight was in response to the buy side suggesting that while the ICD, you know 10 code and you know claims database work that we did is helpful you know they there was recommendation that we do confirmatory work around those patients and so we sent an arbitrary number of a thousand we went out and confirmed them they're there and our conviction and confidence and not only a path to approval in November is is high but our conviction around the market um uh and the market size is um is is high so we've already brought on our 23 person sales team they're out every day finding patients you know getting them you know ready and doing market development work um obviously market development work until approval um so non you know non non-promotional but um just doing general market development disease state awareness work and it's very clear in conversations with physicians that autoimmune patients are they are being diagnosed and they're in dire need of you know some approved therapeutic so Braden you want to comment yeah I think
you stated it well I mean we have a high degree of confidence in the market opportunity from the claims database work and the way you operationalize a launch is you take those data and you leverage it as targeting information cutting territories as Matt mentioned we have 23 rare disease specialists on board already and they're out there profiling accounts they're knocking on doors they're confirming that the patients and the claims that came in from a location the patient's still being actively managed at that location by that physician or they may be at a different location or being actively managed by a different physician so with the time that we have now between today when the in the field force came on and potential approval in November you know they're doing that work such that when knock on wood if we're fortunate enough to have approval that they'll know exactly where to go in the early stages but it's important to remember that and Matt's mentioned this that there's a process of patients coming in to get assessed by their physician again by the prescription actually being written and then adjudicating that claim and then early on in the launch there's no policies in place you're doing that in a very manual basis so there's going to be some time between you know when patients are identified and prescribed to when they actually get on drug as well and that's part of the process that you'll start to see in early 27 and
beyond okay and I I looked at the consensus numbers for 2027 I think it's like 70 million I mean maybe that's 150 patients if they started on day one it's not going to be the case of but like my question to you is it let's just say 300 patients were needed in 2027 you feel very confident about that you know
No, I think so consensus, which you highlighted, we think is, you know, a manageable expectation. And I'll leave it at that.
Very good. And so bigger picture, how should, you know, are there any precedents or launch analogs you've been thinking about that could be similar here of a situation?
So on a nonspecific basis, the answer is yes. This is a team, you know, this group of people and many others on the Samara team. We are firm believers in precedent analysis, right, and keeping our eyes and ears open about what has worked and what hasn't. And there have been numerous recent orphan rare disease launches that we've taken great learnings from. So, for example, I think the way to think about it is, you know, what will be the, you know, pre-launch metrics that we're going to, you know, talk through, talk about, what are going to be the post-launch metrics, and we're being very, very thoughtful about what those are and when and why. You know, we appreciate that the market is going to want and need some metrics to be able to anchor on, but I also, you know, feel strongly that, you know, we need to be really choiceful about, you know, what direction we point everybody in and, you know, kind of pace and pulse that over time.
Thank you. And so interestingly, as we think about ex-US, I think in the UK side of things, the Mulberry could be approved in Q4 of this year as well. And then I think EU, it could be approved in Q1, 2027. So do you intend to launch in those regions by yourselves in 2027?
Well, so the EU and UK strategy at a very high level is, given some of the policy-related issues that our industry is dealing with, for example, MFN, the point of departure is really do no harm to the U.S. launch opportunity. Now, in parallel to that, it's very critical that we continue to move the Mulbrevy applications forward in both Europe and UK, which we are, And because there are, you know, a significant number of patients, autoimmune patients, in dire need of a chronic therapeutic like Mulbrevy in both of those, you know, geographies. So we'll continue to drive them forward to approval. In parallel to that, do the baseline work, especially around some of the HTA prep that we know will be valuable regardless of the MFN kind of clarity or lack thereof that may be forthcoming. And then we'll sort out timing related to launch once we have additional clarity. We do intend to launch in both the EU and UK on our own because we can. We have a team that's been there and done it. We can do it in a very capital and labor-efficient way. But timing is still to be determined based on, you know, again, clarity around or additional clarity around the policy-related issues.
Yeah, okay. And then bigger picture strategy question. Lifecycle management for mobile review. any intention to expand to other indications or any intention to bring something from the pipeline and introduce that as you're launching?
So life cycle management, we're keeping the market as well as the organization squarely focused on autoimmune PAP. We have a ton of opportunity, huge opportunity and a ton of work to do related to autoimmune PAP. So that doesn't mean that we're not evaluating other potential opportunities around life cycle management. It just means that right now when you think about capital deployment as well as energy focus, it's about autoimmune PAP. The second part of the question is, you know, stay tuned because success with Mulbrevy in autoimmune pap is going to create great you know great optionality for the organization but we must be successful and we will be with mulbrevy great thank
you very much for all the updates and good luck on the PDUFA later this year so thank you