Okay, we're going to get started with our next session. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies. It's my pleasure to have the Savara team with me today. To my direct left is Rob Lutz, COO. To his left is Matt Pauls, Chairman and CEO. And to Matt's left is Sid Advant, EVP of Technical Operations. Welcome, all of you.
Thanks very much.
As always, maybe for those who are less familiar with the Savara story, can you please give us a brief introduction about what you're working on for MOLBREEVI and then the catalyst flow over the next 12 months?
Yeah, sure. First of all, thanks, Andrew, and to Jefferies for the invitation to participate. We're glad to be here. We'll do quick intros, and per the question and request, we'll then provide a quick overview and then catalysts over the next 12 months. Matt Pauls, Chair and CEO of Savara. And Rob?
Hi, I'm Rob Lutz. I'm the Chief Operating Officer of Savara. I've been with the company for over two years now, and I've been working in the industry for well north of 20. We'll leave it at that.
Hi, everyone. Sid Advant, EVP of Global Tech Ops. I've been with Savara over a year and have been in the biotech industry for 30-plus years, both on the sponsor side and actually also on the CDMO side.
Thanks very much. Savara is an orphan rare disease company focused in the rare pulmonary space. It's a single asset company, and the asset is molgramostim inhalation solution. MOLBREEVI is the pending brand name. We have, last the middle of last summer, reported positive phase 3 data for IMPALA-2 for MOLBREEVI, which was a 48-week placebo-controlled trial of 164 patients enrolled for autoimmune pulmonary alveolar proteinosis, or today we'll refer to it as APAP. We'll talk in more detail about the results, but again, positive results on the primary endpoint of DLCO, as well as positive results on really all of the key secondary endpoints at different time points of 24 weeks and 48 weeks. Over the next 12 months, we will be resubmitting the BLA, and that will be in the fourth quarter of this year.
A more narrow timeframe will be provided as we get into the end of the summer, beginning of the fall. We will refile in the fourth quarter of this year. We anticipate priority review, and that would put U.S. PDUFA date in the middle of the year, in that range, plus or minus a couple of months.
Great. One big picture question before we dig into the latest news is, help us frame the peak sales opportunity for MOLBREEVI in this indication. How many patients in the U.S., and what do you think the price ultimately could be based on the data that you've generated and the unmet need here?
Sure. Thanks for that question, Andrew. In the United States, we have done multiple rounds of claims database analysis and have a high level of conviction and confidence that in the United States, there are at least 3,600 patients currently diagnosed with APAP. We are in the process of confirming those patients through personal outreach to the physicians, because of course, we know based on the claims database work whom the physicians are. We are confirming that those patients are currently still being treated by those said physicians. As of today, we have well over 500 patients confirmed. We have guided to an arbitrary number of a very healthy number of at least 1,000 patients that we have line of sight into by launch. Now that we have a little more time, of course, we will be driving hard to identify, confirm even more patients than that.
In parallel to that, in the same claims database analysis work that we have done, we also took the learnings from the 3,600 or so patients of the confirmed diagnosed, and we applied those machine learning kind of algorithmic characteristics of those patients to the full database. We believe there's probably at least 3,700 or so currently undiagnosed APAP patients. We think the market at a point of departure is probably double what the current diagnosed population is.
The price point?
Yeah, price point. We've done, again, multiple rounds of pricing research. In the United States, we've guided to a price range somewhere in the $300,000-$500,000 per patient per year. We believe within that range that there's probably real pricing power. While it's a broad range, we think that there's pricing opportunity there.
Okay. Maybe a couple of questions in the clinical data, and then we'll move to the BLA situation. Is, will this be a first-line therapy? How convinced are you this will be a first-line therapy if approved ultimately? Will this also be a chronic therapy? Based on the dataset that you've seen so far, what makes you convinced this will be a chronic therapy?
Yeah, thanks again for the question, Andrew. I think the way to look at autoimmune PAP is that this is, unfortunately for patients, we believe a lifelong battle that they're going to have. There's nothing that is curative. It is, by definition, autoimmune. How, why, when, where patients are afflicted with it, we don't really know. I think the way to think about what patients, diagnosed patients, would be eligible for therapy, we believe that all patients will be offered MOLBREEVI based on feedback that we've gotten from physicians. It actually is very logical.
If a patient is symptomatic enough to seek out a diagnosis and they feel bad enough to be able to hunt down this diagnosis, which can take 12 to 24 months, it's a long journey, there's something happening, whether it be breathlessness that's getting worse, chronic cough, lung infection that's not clearing, or a combination of all of the aforementioned. Patients are looking for not only a diagnosis, but something to help them feel better. Given the fact that we believe that MOLBREEVI has proven to address the pathophysiology of the disease, being defined as helping to turn on the gas exchange signal so that the alveolus starts to function appropriately and help the macrophages address the surfactant burden issue, we believe that patients are going to start on this early in the course of their disease.
Hopefully, it's going to help either slow down or the potential outcome for them down the road. Ultimately, patients, what they don't want to do is they don't want lung lavages. Lung lavages are not a chronic therapeutic answer.
Right. Along the way, you've actually shared some very long-term four- to five-year outcomes data on maybe a handful of patients. When can we expect to see more long-term data from your phase three open-label portion?
Sure. As a reminder, for IMPALA-2, we enrolled 164 patients in the 48-week placebo-controlled trial. 159 of 164 completed the 48-week portion of the trial. 159 of 159, so 100% of those patients rolled into the open-label extension, which is still ongoing. We extended it to 96 weeks. That is ongoing. You can expect more data in the future, of course, but we still have patients in the OLE.
Okay. So, then with the BLA situation, can you just remind us or tell us what exactly happened? Is this the FDA being more stringent, or is it some unfortunate oversight that you may have had that caused this RTF a couple of weeks ago?
Sure. Rob, do you want to take that?
Sure. Before we get into some of those specifics, Andrew, I just wanted to level set with everyone on what the background here with the refusal to file we received recently is. I'd like to start by what it is and what it isn't. It is related to CMC in-process confirmatory testing. Just to be clear, it's not related to the need for additional clinical trials, nor is it related to safety concerns. It's also not related to CMC inconsistencies or CMC issues. Let me take a step back and just give the background a bit here. We manufacture our drug substance, which then becomes turned into our drug product.
When we do that, at the end of the manufacture of the drug substance, it gets tested against a variety, a battery, if you will, of specifications to make sure it is what it is and it's appropriate for use, and we release it. We've been doing that consistently during the course of our clinical execution. We've been making the batches and consistently releasing them against these specifications. When you're shifting from a clinical stage program to commercial stages, there's additional scrutiny of your production process. We thought and believe that it was possible the FDA along the way would ask us for what's called in-process testing confirmatory data. That's where, beyond testing the drug substance at the end, in the intermediate stages, you also test to ensure that it's meeting specifications.
It's additional kind of extra processing tests that you do as you move to commercial stages. Given that we've consistently made the drug substance at the end, we are confident that the in-process testing will also show that we're meeting specifications and we go forward.
I see.
Now, let me just keep going if you would. The next step in this is we believed, and our external advisors advised us as well, that this in-process testing could be done and submitted potentially as part of the BLA review process. The FDA has significant established regulatory flexibility in CMC when you have an unmet need and breakthrough designated product like we have. We thought with that flexibility, we'd submit along the way. We were surprised recently when they came forward and required this information to be submitted as part of the original package upfront. That leads us to where we are today.
I see. And by inference, for you to say you're submitting Q4, this all should be done in, let's call it Q3?
Yes.
Okay. And remind us, you're working with CDER with a D, not CBER, with Pulmonology Division?
DPAC, yep.
Okay. Okay. You are scheduling a type A meeting. When exactly does that happen? When does that complete? When do you get back to the street on any updates, if any?
Yeah, sure. Within 30 days of the RTF, we will submit a type A meeting request. When you do that, you also submit the briefing package. That will be in the next few weeks. The agency will grant the meeting within 30 days after that. You will have meeting minutes within 30 days after that. Back up to last week, roll forward within 90 days from last week, we will have meeting minutes and be able to provide some additional clarity. Just to make sure that we're all aligned on what that is, it is, one, we have two drug substance partners. Our primary, which we've been talking about, is GEMA based in Argentina, who we've been working with for, I guess, the company's been working with them for almost 10 years.
They've produced over 15 clinical batches consistently and supplied both IMPALA and IMPALA-2 at scale, at quality, all of the above. In parallel to that, we are in the final stages of completing a tech transfer to FUJIFILM based in the U.K. Sid, do you want to just quickly talk through the tech transfer process?
Yep, absolutely. Thanks, Matt. As part of the tech transfer, we typically start with some of our development activities. Those have been completed. We then make sure that the process can actually run at scale. We have completed those activities as well. Where we are right now is from a PPQ campaign, upstream batches have been completed, three PPQ batches. We are almost two-thirds of the way finished with the downstream campaign. As part of the entire tech transfer, what we have to generate is analytical comparability. That all is ongoing. That converges in the third quarter completion.
Okay. And then, would you plan to still refile in Q4 with GEMA as the primary, or would you consider FUJIFILM as the primary supplier then?
It's to be determined. I think based on the delay, there now is this real opportunity to potentially make some choices about what the sequence is. Is it one first, the other second as a post-approval supplement if you want to continue to dual source? Would there be a scenario where you would file with both? Still to be determined. I think the takeaway here is we are now in a position, unfortunately, due to the blip that we've experienced, we are now in a position to be able to have what we believe to be some really interesting choices. It will be determined, the final choice will be determined based on the highest probability of success in filing as soon as we can. That's it, bottom line. Stay tuned.
In the hypothetical scenario where you filed both, does that double the risk, or does that half the risk?
It's still to be determined. Yeah. Again, I go back to we will make the decision based on highest POS, shortest amount of time. I think the important note here is that this team had the forethought to put in place and invest behind a tech transfer that is now in the final stages and provides high level of confidence for us on the near-term go forward with FUJIFILM.
To be clear, big picture, the basis of the RTF is not it does not support the notion that GEMA cannot be trusted or unreliable, to be clear.
Absolutely not. We have a high level of confidence in GEMA being able to be approvable. We stand by that. However, we are now in a position where we feel confident that we're going to have two drug substance partners that we have high level of confidence in. We think a high-quality fact pattern that we have to deal with.
Right. I know you want to move as fast as possible. Could you actually surprise the street and refile actually in Q3? Is that a possibility?
Fourth quarter.
Okay. All right. I guess maybe I mean, I wanted to ask, how are we so sure this won't happen again? I don't know what would you say to that if an investor were to say, how are you so sure there will not be an RTF again?
Yeah, this was a single issue for the RTF that's solvable. It's solvable in two ways. One is based on the data that we're producing at GEMA that was requested, will be completed August-September timeframe. That answers the question around the single reason for the RTF. In parallel, I should note, just as a side note, that as part of the tech transfer and move to commercial at FUJIFILM, all of these data that were requested based on the RTF, they're already being collected and accumulated at FUJIFILM as part of their SOP, standard operating procedure. We also have the answer to the RTF question at FUJIFILM.
I see. Maybe one more question on the tech transfer for FUJIFILM. When exactly did that start? You mentioned you've completed the upstream PPQ. There's downstream PPQ right now. Is there anything else left to complete this tech transfer?
We started the tech transfer process, I believe, in the beginning of 2024. We will be approaching about 18 months or so. Anything else, Sid, that you want to cover?
No, I think we basically will finish the downstream PPQ campaign and continue to generate all the analytical data that will support the comparability.
Okay. That's it?
Yeah. I'll also note that the tech transfer process is at the same scale as GEMA, 100 liters, and exact same process. Those are both very important as you're moving forward on a tech transfer.
Great. Okay. I think that's very clear then. Should you refile in fourth quarter, it gets accepted, like you mentioned earlier with the priority review amid 2026 PDUFA. Would you expect an adcom in the near term, in the meantime?
We have been planning for and will continue to plan for and prepare for an adcom if and until we're told otherwise. As the first therapeutic for this orphan rare disease condition, we think it's good form to be ready. We have already been in process of planning and prepping for it. We will continue to unless we're informed that it's not necessary.
As this US refiling is going on, you did mention MAA filings should occur year-end. Is that still on track? When can we expect other regulatory filings elsewhere?
Yeah. Europe and U.K., both filings will occur by the end of this year. They're on track. Other geographies, we haven't put a stake in the ground yet. By year-end, Europe and U.K.
Okay. You do have, however, buy-in from regulatory authorities worldwide that as long as this IMPALA-2 was successful, phase three, you can file. It's just you're just deciding when to file, to be clear.
Yeah. We believe based on the results of IMPALA-2 and, of course, the supportive nature of the IMPALA data, we are confident. We believe there's a path to approvability. We are endeavoring to get MOLBREEVI in the hands of physicians around the world as fast as we possibly can. We are driving hard.
Great. Maybe in the last five minutes then, let's go back to the commercial side of things. As I think about competition, there is another drug, Leukine, approved in Japan for APAP. What's to say they don't enter the U.S. to compete with you? If they do, how is your drug different exactly?
Yeah. I think the way to—let's talk a little bit about the differences. Let me just highlight from—so MOLBREEVI is a once-a-day, it's administered once a day versus alternative therapy of twice a day. It is delivered in a proprietary bespoke nebulizer that is high efficiency that's developed for MOLBREEVI, a large molecule to be delivered. I think the other piece here is look at the body of evidence. MOLBREEVI is the longest, deepest studied therapeutic ever in comparison. Forty-eight-week placebo-controlled trial with 164 subjects is by far the biggest and longest study ever in the history of APAP. I think the way to think about—I can't comment on—and I won't comment on regulatory probability of success of other therapeutics. I think the bar is very high. It was established via our program. That's IMPALA-2 and IMPALA. I'll leave it at that.
Yeah. Okay. You mentioned earlier in the comments, you do right now have line of sight to 500 diagnosed patients. Correct me if I'm wrong. Is that the case?
Over 500, yes.
Over 500. I have in my notes you did have line of sight to 450 as of January 2025. The original plan was to have 1,000 by the time this was approved in early 2026. It could be shifted by a little. Are you willing to revise your number of direct line of sight patients over 1,000 at this juncture?
If we had committed to having line of sight into at least 1,000 patients by launch at the end of this year, we surely better have line of sight into more than 1,000 patients. I am not going to say anything more than that. We have a small group of people who are, as we speak, out confirming patients on a daily basis. I think we are going to be in a place that there is going to be a significant bolus of patients that will be ready for therapy upon approval.
Right. I mean, bolus meaning if you truly did have 1,000 on a $400,000 net price, obviously you have pricing power. But just hypothetically, it's $400 million in first-year sales.
Yeah. I mean, I think it's safe to assume that that's probably a real stretch. The point is that when you were confirming that the patients are there and just stay tuned, I think the setup opportunity here is real. Meaning we know patients are ready for therapy. As a reminder, we have a significant number of patients in the open-label extension in the United States from IMPALA-2. We also have not talked details around numbers related to the EAP. There is an EAP that's up and running that's obviously highly regulated. It's being utilized. We know that the patient community is anxiously awaiting the approval of MOLBREEVI.
I see. Some investors wonder how many whole lung lavages are being done in the U.S. each year. Do you have a good number?
We don't. It's a very difficult procedure, rescue procedure to be able to kind of back into. I will remind you that in both IMPALA and IMPALA-2, lung lavage was allowed in an unrestricted manner. For example, there were no parameters around it. It was purely up to physician and patient decision and choice. In both of those trials, only approximately 10% of patients had a lung lavage. That's one way to look at it. It's a rescue procedure. It will always be there. That's a good thing for patients. We're just hopeful that with MOLBREEVI, they'll have the opportunity to have a chronic therapeutic and know that they always have a rescue therapy if they need it.
Great. Last 30 seconds. We've been talking about the diagnosed patient population. Like you said, there's an undiagnosed population, 3,700 in the U.S. possibly. You have an antibody test. When will you be prepared to share the number of patients that you found with that test?
Yes. As we get closer to launch, we think that that will make sense. We are currently in the process of working through a scale-up plan for our ILD clinic pilot. We believe that based on the dry blood spot test availability, the simplicity of it, and the scalability of it, that in the ILD clinics, there is an enriched patient population of undiagnosed APAP patients. We feel strongly about that. More details forthcoming.
All right. Thank you so much for your time and the updates. It was very clear. Thank you everyone for listening.
Thank you.