Good afternoon, everyone, and thank you for joining the 2025 HC Wainwright 27th Annual Global Investment Conference. I'm Dr. Jay Montgomery, an Associate Biotech Research Analyst at the firm, and I'd like you to please join me in welcoming Matt Pauls, CEO, and Braden Parker, CCO of Savara. Matt and Braden?
Thank you very much. Again, I'm Matt Pauls, Chair and CEO of Savara, and now joined by my colleague Braden Parker, Chief Commercial Officer. First of all, thanks to HC Wainwright for the invitation to participate today. We greatly appreciate it. Standard Safe Harbor statement and for your assessment regarding potential forward-looking statements. Savara is a single-asset rare disease company focused squarely in rare lung, rare pulmonary diseases. Our single asset, Mobrevi, or morgamostim inhalation solution, which we'll talk about in more detail, forthcoming part of the presentation, is being studied and soon to be resubmitted a BLA for autoimmune pulmonary alveolar proteinosis or autoimmune PAP. What is autoimmune PAP? Autoimmune PAP is a serious long-term chronic lung disease, and it's a disease of alveolar macrophage dysfunction. It's caused by GMCSF autoantibodies that block signaling of GMCSF and therefore reduce surfactant clearance.
When the movement of oxygen is blocked, surfactant accumulates in the lungs, and it causes a whole host of byproduct issues, which we again will talk about in the near term here. You'll see on the right-hand side that in the normal versus abnormal alveolus, the alveoli need surfactant to keep from collapsing. They just need to make, we need to make sure that there's the right amount of surfactant or homeostasis so that the structure is maintained, but there's not too much. As I mentioned, autoimmune PAP, it's a rare long-term lung disease, and the cardinal manifestation or symptoms of the disease are mainly progressive shortness of breath or dyspnea that just gets worse over time as surfactant burden and surfactant accumulates. There's also chronic cough, very often increased risk of lung infection that doesn't clear. Patients often feel fatigued and have decreased exercise tolerance.
Unfortunately for some patients, it progresses to fibrosis, and some patients, in fact, require a lung transplant. I want to emphasize that there are no approved drugs in the U.S. or Europe for autoimmune PAP, and there's really only one rescue procedure, which is an invasive procedure called whole lung lavage. Lung lavage is performed in very few tertiary centers or specialty centers. It's not standardized. Effectively, what a lung lavage is, is a patient comes in, they go under general anesthesia, it requires hospitalization. It's hours in length. It is effectively power washing of the lungs. Reducing the volume of surfactant in lungs by using 20 to 30 liters of saline to, again, power wash the lungs is a burdensome and very taxing procedure for patients. Most importantly, it doesn't address the underlying pathophysiology of the disease. It does not fix the gas exchange issue.
It is purely, for many patients, a temporary relief because you're reducing surfactant burden. Moving to Mobrevi, or morgamostim inhalation solution, it is a drug-device combination. It is 300 micrograms inhaled once a day. It is a novel inhaled biologic, and it's delivered through a proprietary eFlow nebulizer system that has been developed in partnership with our partner, PARI. It is optimized for a large molecule biologic like Mobrevi. PARI is a well-respected partner in the nebulizer manufacturing realm. In fact, they have five FDA-approved nebulizers based on this same eFlow technology. The nebulization time is approximately five minutes, and between setup, nebulization time, and cleanup, all in about 20 minutes or so once a day. Once a day, five minutes, 300 micrograms inhaled on a daily basis. In the middle of 2024, we announced positive results for our single global phase 3 registrational trial called Impala 2.
The primary endpoint, which was met, was change from baseline to week 24 in DLCO and measurement of gas exchange. The trial design was a 48-week placebo-controlled trial, but the look back on the primary endpoint was to 24 weeks. The DLCO was statistically positive at 24 weeks. DLCO was also maintained statistically positive at 48 weeks. There was durability of effect in addressing the pathophysiology measured by DLCO, which is the gas exchange measurement. There were also other key secondary endpoints that were either statistically significant or nominally significant, including the St. George’s Respiratory Questionnaire at week 24. Also, the SGRQ or St. George’s Respiratory Questionnaire activity score at week 24. At week 48, exercise capacity as measured by the treadmill test was also nominally significant.
We believe that both DLCO, a surrogate endpoint measurement, is supported, we think clearly, by SGRQ total activity and exercise capacity at various time points between 24 and 48 weeks. Safety and tolerability, low discontinuation rate of only 3%. None of those discontinuations were due to drug-related adverse events, very well tolerated. Importantly, of the 159 subjects who completed the 48-week placebo-controlled portion of the trial, all 159 rolled into the open-label extension, so 100% of patients. These results, Impala 2, were just recently, in the last month, published in the New England Journal of Medicine. The prior study, the phase 2-3 study, Impala, was also published in the New England Journal of Medicine, and that occurred in the fall of 2020.
Both Impala, as well as most recently, Impala 2, were published in the New England Journal of Medicine. There is also a published case series of five APAP patients who received Mobrevi through single-patient access. These patients had a mean duration of therapy over four years, and prior to taking Mobrevi, four patients had at least one whole lung lavage. Fortunately for these patients, after post-treatment, zero patients required a whole lung lavage after greater than one year of Mobrevi. The long-term effect on this cohort of five patients has been long and sustained and rather remarkable. Regulatory and intellectual property timelines: the BLA in the U.S. will be resubmitted this December. Assuming a 60-day review prior to filing and if priority review is assigned, that would put PDUFA in the August timeframe of 2026.
In the EU and UK, the MAA will be submitted in the first quarter in both the EU and UK, and there is potential approval in the first quarter of 2027. In the United States, Mobrevi has orphan drug designation, fast track designation, and breakthrough therapy designation. In Europe, orphan drug designation and both innovation passport and promising innovative medicine designation in the UK. If approved in the U.S., there will be regulatory exclusivity afforded Mobrevi of 12 years, and we are also prosecuting some patents globally. There is also an exclusive license on the eFlow nebulizer system with PARI for Mobrevi and APAP, and a pending joint patent application with PARI for the drug-device combo.
From a commercial perspective, Braden and team have done really great work over the last couple of years, including launching a disease state awareness campaign here in the United States, both for physicians as well as patients. Almost two years ago, just under two years ago, we launched APAP ClearPath, which is a no-charge third-party testing program in the U.S. It was originally launched with a serum-based test. We then evolved it into a dry blood spot test. This free, no-charge third-party testing program is available in the U.S. as a dry blood spot test and serum if one chooses. The dry blood spot test is a few drops of blood in a card. It's mailed into the lab, and within seven days, the physician receives results on whether the patient is positive or negative, and if positive, the titer level.
Based on market research that we've done across stakeholder audiences, physicians, payers, and patients are all very interested in the potential of Mobrevi, assuming that it is approved. Physicians are, you know, over 80% pulmonologists are keen to prescribe Mobrevi, regardless of severity of the disease. Payers intend to cover Mobrevi, and our pricing corridor, although it says $3,000 to $500,000 annually here, it's actually, we've narrowed that down to a pricing corridor of $400,000 to $500,000 per patient per year in the U.S. We believe there's real pricing power here. Patients are very interested in the potential for Mobrevi. The question is, how big is the opportunity? The autoimmune PAP/Epi literature has a range of, at the low end, 6 per 1 million to the high end of 26 per 1 million. A pretty broad range.
In the United States, we recently, again, Braden and team recently conducted a revised new U.S. claims data analysis. The previous work that was done in 2023 suggested that there were approximately 3,600 or so APAP patients in the United States. Our new claims database analysis actually suggests that it's about 50% bigger, or there's 5,500 or so identified patients. You'll see on the right-hand side the rigor that was conducted related to the claims data analysis. We really made sure that we tortured the data and are highly confident in the 5,500 identified patients. What's the difference between the 2023 analysis and 2025? Pretty significant, although the lines covered are about the same. In the newest elegant data set, it had both open and closed sources, and the data capture was about three times greater in the most recent analysis compared to the previous analysis.
These data also, by the way, there could potentially be a little bit of upside given the fact that it was not projected for the total U.S. population. We currently have four market development managers out in the field as we speak, and they are doing confirmatory work, what we call line of sight, and gaining line of sight into patients whom, through the physicians who do the diagnosing and treatment, just confirming that those physicians do have, in fact, those patients. We're on track to, by year-end, be in the 1,000 or greater patients' line of sight. Bottom line is we're out, we have boots on the ground, and we're out ensuring that the claims data analysis is holding up nicely, and it is. We're looking forward to continuing to gain line of sight on patients. In Europe and UK, the opportunity also is very real, as you'll see.
Between the EU4 and UK, over 5,000 patients estimated as the total addressable market. I will also highlight that there are currently 62 patients in Europe that are enrolled in the Impala 2 open-label extension. A well-organized, well-structured APAP market. We will be driving forward to get the MAA in both UK and EU submitted in the first quarter. A real potential exciting opportunity in the EU and UK. From a financial perspective, we have guided to having cash into Q1 2027 with $146 million on the balance sheet as of the end of the second quarter. We have strong investor support and are a well-covered company. In summary, both the near and the long-term opportunity for APAP in the U.S. specifically is sizable, with what we believe to be a real robust opportunity of 5,500 or so identified autoimmune PAP patients in the United States.
Again, an attractive price point range of $400,000 to $500,000 between regulatory exclusivity and a patent estate that's being prosecuted. We believe that there's real potential upon approval for Mobrevi to generate durable long-term revenue here in the U.S. and also in EU and UK and potentially Asia-Pacific. With that, I thank you all for attending. I guess we do have a couple of minutes for questions if there are any. Yes, please.
Hold on. I'll get ready. CEO from HC Wainwright PA.
Hey, can you elaborate on the corporate reasons for HC Wainwright?
Numerous team members live in the area. It's a great corridor for both biotech and pharma talent acquisition. Thanks.