Hello, everyone. Good morning. My name is Li Chen. Welcome to the H.C. Wainwright Global Investment Conference. I'm an Equity Research Associate. Now I'd like to welcome Rob Lutz, Chief Operating Officer of Savara, a clinical-stage biotech company focusing on rare respiratory diseases. Rob, please go ahead.
Thank you very much. Appreciate it, and welcome, everybody. As it was said, I'm Rob Lutz. I'm the Chief Operating Officer of Savara. I'm joined today by Dave Lowrance, who's our Chief Financial Officer. Did that just change? Am I okay?
Yeah.
Great. Awesome. We'll jump in. So, in the Safe Harbor slide here, please take note of our information and background. Next slide, please. This is a summary of our team. As you can see, we have a deep executive team with significant experience in operating a biotech company. Next slide. All right, so just as starting with a little summary, so Savara is focused on a single inhaled biologic called molgramostim, which has completed a successful global phase 3 program in APAP.
We'll talk about it in a second. It's a rare interstitial lung disease. The BLA submission for the drug is expected in the first half of 2025. We believe the global commercial potential is significant, with 5,000 patients in the U.S. diagnosed, and pricing at perhaps $300,000-$500,000 per year per patient, consistent with rare disease analogues. It's also worth noting that as an inhaled biologic, molgramostim has potential for durable long-term revenue, with biosimilar competition being unlikely.
Okay, next slide. Thank you. All right, a little background on APAP first. APAP is an autoimmune disease of the alveolar macrophage. In APAP, neutralizing antibodies to granulocyte-macrophage colony-stimulating factor, or GM-CSF for short, are produced, thereby decreasing alveolar macrophage function, which results in an accumulation of surfactant in the lungs over time. Next slide.
This surfactant accumulation decreases gas exchange in the lungs, resulting in progressive breathlessness, cough and sputum production, lung infections, decreases in oxygenation, fatigue, decreased tolerance for exercise, and can even result in fibrosis and lung transplant. Unfortunately, even lung transplant is just a temporary fix because the GM-CSF antibodies remain and cause surfactant to build up in the new lungs. There are no approved drugs for APAP. The only treatment option is a procedure called lung lavage.
Next slide. Lung lavage, which is pictured here, is a barbaric procedure where patients basically have their lungs power washed in an operating room. On the right, you can see the result of the power washing starts with a gunky, surfactant-filled fluid and ultimately gets clearer and clearer with multiple, you know, liters of fluid going through.
The procedure is traumatizing for the lung, as you can imagine, and requires percussion to loosen the surfactant, so it often leads to stays in the ICU and/or complications, including rib fractures, pneumothorax, and hydrothorax. Sadly, lung lavage is also a temporary fix. The surfactant buildup returns since the treatment does not address the root cause of the surfactant buildup, which is the lack of GM-CSF in the lungs. Next slide, please. The symptoms of APAP, which we discussed, significantly impact a patient's health.
Research shows that APAP patients have significantly higher rates of comorbidities and greater need for healthcare interventions than matched peers, as illustrated in a series of boxes on this slide. Next slide, please. Our proposed treatment for APAP, molgramostim, is recombinant GM-CSF in a liquid formulation that is nebulized and delivered straight to the lungs in an attempt to replace the GM-CSF that is eliminated by the neutralizing antibody.
We pair molgramostim with a customized nebulizer that we are sourcing through an exclusive contract with our partner, PARI. PARI is a well-established nebulizer manufacturer with five FDA-approved nebulizers on the market. Next slide, please. Now we'll turn to the results of our recent phase III clinical trial, IMPALA-2. IMPALA-2 was a phase III double-blind, two-arm, placebo-controlled trial. The primary endpoint was DLCO, which stands for diffusion capacity of the lungs for carbon monoxide.
We measured that at week twenty-four for the primary. DLCO is a well-established measurement of lung function. The trial remained blind through week 48, test for durability, but again, our primary endpoint was at week 24.
We also measured multiple secondary endpoints to confirm the clinical benefit beyond DLCO. Measures we tested included SGRQ, which is the St. George's Respiratory Questionnaire, which is a we'll talk more about it, but it's a well-known measure in COPD, originally to look at lung function and the effects of lung disease. We measured that at weeks 24 and 48. We measured SGRQ activity, which is a subscale of the SGRQ, focused obviously on activities, also at weeks 24 and 48.
And thirdly, we measured exercise capacity using a treadmill test with a modified Bruce protocol. We also measured this at week 24 and 48. Next slide, please. First, we'll look at the patient disposition from IMPALA-2, and I point out a couple of things in particular. So first, discontinuation in the double-blind period was 3%, five patients in both arms combined.
You'll see there were two discontinuations in the treatment arm. Neither was considered drug-related. Secondly, we saw 100% of patients who were eligible decided to continue into the open enrollment, open label extension after a full year of the trial. And third, you'll note we screened 286 patients to ultimately randomize 164. So 122 were ineligible for the trial, didn't pass the screening. Most of those who were ineligible had a DLCO above the 70% DLCO maximum.
We consider this a sign of unmet need in APAP, as even patients with higher than 70% DLCO scores wanted to be in this year-long trial, where they had a 50/50 chance of being on placebo for a year. So we, again, just to summarize, we had many patients interested in this trial, even though they didn't make the cutoff. Next slide, please. Here we present a little background on the demographics between the treatment arms. It was well-balanced and fairly benign in terms of interest, so we'll move on to the next slide.
On this slide, we present the data on our primary endpoint. First, to orient, on the left, you'll see a line graph with DLCO measurements of the two treatment arms at various time points, showing the 95% confidence intervals. On the right, you'll see a bar graph showing the results for each arm at weeks 24 and 48, and a bar graph showing the least squares mean differences, as well as the p-value of the differences.
If you look at the p-values, you can see that molgramostim was superior to placebo on the change from baseline in DLCO at both weeks 24 and 48. And with those p-values, both results were statistically significant. Next slide, please. Now, looking at our first secondary endpoint, SGRQ total, we can see here that the change from baseline SGRQ was statistically significantly better at week 24, as you can see on the right with the p-value, and the positive trend continued at week 48.
You can see both in the, in the p-value and with the line graph. It is worth noting that IMPALA-2 was not powered for any of the secondary endpoints, so seeing significant results at week 24 and 48 was gratifying to us. Slide. Now, moving on to SGRQ activity as another secondary. Again, one can see the separation of the molgramostim treated patients from the placebo arm. The change from baseline on SGRQ activities was nominally stat sig at week 24, and the positive trend continued at week 48.
Lastly, in terms of the secondaries, you can see that with exercise capacity, the treatment arm separated from placebo, and at week 48, exercise capacity for the treatment arm was nominally significant compared to the placebo arm. We had not measured exercise capacity using this test previously, so we're very pleased to see these results and believe this demonstrates and supports.
In general, all the secondary endpoints generally support the idea that the DLCO measurement of gas exchange also demonstrate clinical benefit to the patients in the respiratory questionnaire and in exercise capacity. Here, we're gonna share a little data on lung lavage.
Just as a backgrounder, lung lavage was permitted as a rescue therapy in IMPALA-2 , so we were able to measure what happened when principal investigators and their patients had an opportunity to use lung lavage as a rescue. First thing to note is it was not widely used, so only 10% of patients across the whole trial were given at least one lung lavage, and this is consistent with what we found in the first IMPALA trial, so it's not widely used. So because of that, there's not enough data to draw a significant conclusion from the data.
But that said, we're pleased to see there were fewer lung lavages directionally in the molgramostim arm, with 7.4%, versus the placebo arm, where there were 13.3% of patients who had a lung lavage. Next slide, please. Now, turning to safety and tolerability. Overall, the molgramostim-treated patients saw roughly similar levels of treatment-emergent adverse events as the placebo patients saw.
So in our mind, nothing particularly remarkable stands out here. If we go to the next slide, if we look a little more detail in terms of specific adverse events, the AEs that were somewhat more common in the molgramostim arm, although not particularly common, were COVID, nasopharyngitis, and diarrhea. And as a reminder, there are only two discontinuations in the treatment arm of the trial, and neither of those were considered drug-related.
So this slide is a summary of our efficacy data across multiple types of data, including the impact of molgramostim versus placebo on the pulmonary gas exchange, on respiratory health-related quality of life, on patient functionality, and surfactant burden. We're basically just breaking down some of our key data points in those four categories, which are relevant to clinicians in practice and ultimately to the way the drug is working.
I should point out that we've added some additional data on this slide that was recently shared at the European Respiratory Society, ERS, just on Sunday. In particular, we announced that the disease severity score, which you can see in the second row there, improved significantly more in the molgramostim arm compared with placebo. Disease severity is measured through a combination of patient symptoms and partial pressure of oxygen.
We also shared responder data for DLCO and SGRQ versus placebo at various thresholds. These, again, support the top-line data analysis that we had already announced and we went through. In addition, we shared new data on the burden of surfactant as measured by ground glass opacity from chest CT scans. The change from baseline on ground glass opacity was significantly improved in the molgramostim-treated arm versus placebo at week 24.
And it's worth noting that there's nothing on week 48. We didn't measure ground glass opacity or take CT scans at week 48. So it's not that we're leaving the data out, it didn't. We don't have the data. So bottom line, this additional data we announced at ERS continues directionally to show support for what we saw on the top line, and overall supports the direction of the drug is working in APAP. Next slide, please. All right, turning to background on the regulatory.
As I mentioned before, we're working diligently as hard as we can to submit the data as soon as possible. We've announced publicly that our BLA will be in the first half of 2025, and as a reminder, from an exclusivity point, with a biologic in the U.S., we would expect to have 12 years of regulatory exclusivity.
In the EU, we would expect 10 years, given the orphan drug designation, and we're also building a patent estate to provide additional protections, and as we talked about earlier, with an inhaled biologic, there's always the question of when and whether you'd have biosimilar competition anyway. Now we'll turn to the commercial background.
In terms of published literature on epidemiology, there are two studies, primarily, one in Japan and one in the U.S., that showed a similar diagnosed APAP prevalence of about 6-7 per million. However, and as expected with a rare disease like APAP, where you have no approved drug treatments, additional study in Japan showed that with more intense use of antibody testing to look for APAP, diagnosed prevalence in one area, one prefecture, reached 27 per million, or about 4x the original diagnosed prevalence.
As you can see in other rare disease, you know, rare diseases, when you develop a treatment and bring attention to a disease, you often find more patients. That looks like that's possible here in APAP. Next slide, please. To further the analysis, we reanalyzed some claims data in the U.S.
We identified 3,600 diagnosed APAP patients in the U.S. today, so that's approximately more like 10 per million, 10 or more, and then we also used machine learning to identify an additional 1,400 patients, so 5,000 in total, that are highly likely to have APAP but just haven't been diagnosed yet, so they have all the same background, taking the same meds, seeing the same doctors, et cetera.
Look very, very similar in everything, but they don't have the diagnosis yet, and partly, as you can see, that's because it's a long journey to get diagnosed, so it's typically months of hard work to get diagnosed, and, you know, takes a lot of fighting through the healthcare system, so not surprising when you have a rare disease.
We've heard this over and over in rare diseases, people aren't looking for it, so you have to fight through, and it takes a long time to get a diagnosis. So we'll ultimately try to help with that. Next slide, please. So how are we helping? To raise awareness of APAP, we've launched a disease awareness campaign in the U.S., and in the U.S., we've also begun to offer a no-cost GM-CSF antibody test that's readily available now in the U.S., and we're planning to launch that in the EU as well this year.
We're trying to bring attention to, to the disease and offer a way to diagnose that's even easier and free for patients and their physicians. Next slide. All right, so this slide gives an opportunity to provide an overview of the molgramostim commercial opportunity as we see it. To summarize, there's a high unmet need for a safe and efficacious drug treatment for APAP. We've talked about the only option right now is lung lavage. It's not great.
Epidemiologically, we believe there are 6- 10, roughly 6- 10 patients per million currently diagnosed. So in the U.S., that'd be the 3,600 we talked about, and we believe with the no-cost antibody test and disease awareness efforts, that can grow meaningfully, as witnessed by the additional epidemiology literature that suggests there could be as many as 4x as many patients with the disease actually than are diagnosed today. We believe pricing would be consistent with rare disease analogs.
So for example, in the U.S., we believe pricing could be in the $300,000-$500,000 per patient per year range. As we talked about, we believe we could have a durable revenue stream with minimum of 10-12 years of exclusivity, plus, you know, the, the potential that there'd be no biosimilar competition in the long run. Lastly, we believe we can access the APAP opportunity with an orphan disease like commercial infrastructure.
For example, in the U.S., we believe a 15-30-person field-based team could successfully reach the APAP market. Next slide, please. All right, that's the commercial story. Turning to the financials. Next slide. We're well capitalized at the moment, $215 million in pro forma cash and cash equivalents. That pro forma includes cash from the balance sheet on June 30th, plus the proceeds from our July 2024 equity offering, and we've guided that that cash will last through 2026.
And you can see here we've got coverage, including our friends at H.C. Wainwright. Thank you for having us here and inviting us to this, and they're amongst our analysts. Next slide. And that's the basic story. This is a rehash of the summary. So thank you. I think we have a few extra minutes, three extra minutes, so we're happy to take any questions if there's any.
Q&A session, if anyone has questions. If not, thank you for the great presentation, and have a good rest of your day.
Great. Thank you. Thank you all. Appreciate it.