Sedana Medical Aktie

Hello, and welcome to today's FinWire broadcast presentation with Sedana Medical.

[Operator Instructions]

With that said, I'll hand the floor to you. Please go ahead.

Thank you for the introduction, and a warm welcome to our Q1 report 2026. Sometimes the development of a company is shown best in quarters where you're facing some headwinds or adverse conditions. We have been through such a quarter in Q1 with significantly less patients in intensive care units in several of our main markets and also a nationwide strike that is affecting our operations in Spain.

So for the first time since the year after COVID-19, we are seeing a slight sales decline. But despite all of these factors, we have delivered a positive EBITDA on the group level and double-digit EBITDA even in our ex-U.S. business. And of course, I prefer quarters where things go a bit more in our favor or the market environment is at least neutral, but this Q1 really demonstrates that all the work we have done in transforming Sedana Medical into a fully customer-focused company with a very lean backbone and cost structure is now really paying off.

So let's jump right in on Page 3 with the highlights of the quarter and the progress against our 3 priorities: sales growth, profitability and our U.S. journey. Starting with sales. Last year, we reached a new all-time high with SEK 200 million net sales for the full year 2025. That was a good result, but also a very unusual pattern that we saw during the year with 2 very different halves of the year. In the first half, we sold for SEK 107 million. And in the second half, we sold for SEK 93 million. So the first half was 15% higher than the second half.

This follows the pattern we have seen in ICU occupancy last year with a very long and severe flu season with a lot of ICU patients in the first part of 2025, but then low levels from May on all the way to the end of the year. So for this year, this means that we are up against an unusually strong comparator in Q1 and Q2, while the comparator in the second half of this year will be lower. And against that comparator, we had sales of SEK 53 million in Q1, which is an improvement compared to Q4 2025 and still the second best quarter we've ever had, but a slight decline of 2% at constant exchange rates compared to Q1 2025.

Despite that sales decline, we are looking at a profitability situation that I am very pleased with. Group EBITDA was positive with 3% in reported numbers, would have been 5% without the FX headwinds in the quarter. And our ex-U.S. EBITDA was even double digit with 10% in reported numbers or 11% at constant exchange rates. And again, this really shows that we are capable of delivering good bottom line even when the market is going against us. And conversely, once we are looking at a more favorable market conditions again, and we will be back to growth, our profitability has the potential to scale very nicely, thanks to our healthy gross margins.

Gross margins were at 71% in the quarter, which is flat compared to last year, but this is also masking the full truth here because both our lower-margin businesses, so distributor markets and our contract manufacturing represented a higher share of sales this time, which had a negative gross margin effect. But in reality, we are now enjoying significantly lower cost of goods for our main device following the acquisition of Innovatif Cekal, and that has a very positive effect on our gross margin. And we had SEK 81 million on the bank account at the end of the quarter, which will be enough to get us to the U.S.

Speaking about the U.S., this should be actually our last quarterly report before our U.S. submission. Everything is on track. We're still aiming to submit the dossier midyear. And with our 2 successful clinical trials with our Fast Track Designation and a positive pre-NDA meeting, we're very much looking forward to taking the next steps towards approval. During the quarter, we also kicked off our Early Access Program with the first U.S. patients now being treated at Vanderbilt University before the actual market authorization.

If we move to Page 4, please. You see all the work that we have done over the last years condensed in one picture. Starting with the year 2022, the year after COVID-19, when we incurred the biggest loss in the company's history. That was the time when we made it a priority to reach profitability outside the U.S. before launching in the U.S., and we started a turnaround program in which we fundamentally changed how we invest our money. So we made significant cuts in everything that is noncustomer-facing and administrative in nature. Our Swedish headquarter, for example, operates now with less than half of the number of people. And part of that freed up cash, we have then reinvested into strengthening the sales team. So we are much more focused on commercial execution today. We're much more customer-centric as a company, and we have more people in the field overall.

But also here, we've applied a very disciplined and differentiated investment approach where we increased spend in countries that are meeting our profitability targets and show good momentum, but we also cut back rigorously where that is not the case yet. And now you can see the results on this slide, we saw a consistent improvement of our bottom line and actually a bottom line that improved faster than sales grew. So every year, so far, we've been able to do more with less.

We reached EBITDA profitability for the full year 2025 outside the U.S. and now we are looking at double-digit ex-U.S. EBITDA margin and a positive group EBITDA in Q1, which makes this Q1 the best quarter from a profitability perspective that we've ever had.

As you will see on Page 5, this puts us very well on track to deliver on our financial targets for the year. We guided for mid- to high single-digit full year ex-U.S. EBITDA, and now we started the year with 10% or 11% at constant exchange rates. And we also said that we would aim to approach even group level EBITDA breakeven this year, and now we stood at positive 3% after Q1 or 5% at constant exchange rates. And as every year, we are likely to see some seasonality around these numbers, but we are very confident to meet our guidance for the full year.

Then let's look at the performance per region. Let's start with Germany on Page 6. When you have a 15% sales decline in a country where your ambition is to grow sales, you obviously have to analyze very, very closely to what extent this performance is explained by external market factors, but then also very quickly focused back on what you can actually control and what you can change to turn around the trend. The short answer here is that this quarter was heavily influenced by a very different situation in the ICUs during this quarter in Germany compared to last year with significantly less patients being treated.

I will show you the data around this on the next page, so you can more easily calibrate our performance. But internally, we have not spent much time at all complaining about the adverse market conditions, but instead focused on things within our control that will accelerate growth and make us more immune against quarters with low ICU occupancy. So for example, we have strengthened our leadership team with a new colleague who comes with a very impressive track record in growing sales, who will be working across all of our countries actually, so not just Germany. We are working on a territory realignment in Germany to allow for even better focus on high potential accounts, which are typically those who are already customers but don't use our products as much yet as their patient demographics would suggest.

We know that our customers in Germany cover around 70% of ventilator beds in Germany. So this is where most of the growth potential sits. We are also investing more in sales training since many of our field force colleagues are former ICU nurses. They are excellent clinically and probably better than most field forces actually when it comes to clinical skills that are active in intensive care, but there's more we can do in optimizing sales techniques to complement those clinical capabilities. With all of this going on, we will hopefully see the impact, especially in the second half of the year when the comparators, as I said, will become more normalized again.

On the next page, you see a comparison of how the flu season 2024, '25 and the flu season '25, '26 have translated into ICU admissions. It would be obviously wrong to say that there was no flu season this year. There absolutely was, even one with quite high incidents. But what is relevant for us is how many of these patients are becoming so severely sick that they need ICU care and need to be mechanically ventilated. There are different data sources for hospital admissions, ICU occupancy and so forth.

We have analyzed all of them, and we know that the best correlation with our sales is the data you see here. This is Robert Koch Institute reporting weekly numbers of ICU admissions with severe acute respiratory infections. And here, you see those data for this flu season in dark blue compared to the previous flu season in light blue. And what you can clearly see that on average, there were less ICU admissions in Q4 2025 and in Q1 2026 than the year before.

Around the turn of the year, there was a brief period when it looked like this season could become worse than the previous one, and there was also a lot of press coverage around this, as you might have seen. But eventually, we never reached the peak from last year and the decline started much earlier. Bottom line was that we had 22% lower level in Q4 and 15% lower level in Q1. Now our Q1 sales in Germany were affected a bit by a mix of both of these because we typically see a few weeks lag until higher or lower ICU occupancy translates into higher or lower orders. And when the ICUs are more empty, then ICUs tend to order less and also later, which is exactly what happened in Q1. And what came on top here is that this, I would say, mini peak in the end of 2025.

During that period, we had some larger orders come in just before year-end in anticipation of a really bad season, which then didn't materialize and affected reorders in Q1. So that explains why we had a 15% lower sales in Q1. But again, quarters like this will happen. There will also be quarters that go the other way. But in both cases, our focus must be on what we can control. There's nothing we can do about ICU occupancy. So we need to become as independent from this as we possibly can through strong execution and beating the market through some of the initiatives I've been talking about.

On Page 8, you see the performance of our other direct markets. We grew 7%, which is less than the numbers that you're used to. A major factor here is that the country where we typically see most of our growth come from. So Spain was affected by nationwide doctor strikes. Since January, doctors across specialties actually went on strike for 1 week every month, protesting for better working conditions and also better pay. And from what we can see, a resolution of this conflict does not seem very likely in the short term as the demands are quite a bit beyond what the government will be able to accept and the strike weeks have actually already been scheduled into the summer. And during these strike weeks, what happens is that ICUs operate at minimum capacity.

For us, it has been very difficult to get access to customers. We cannot schedule trainings. We cannot follow up. So that's what's been affecting us in the first quarter. What's very, very positive in all of this is that we still saw growth in Spain during the quarter, not maybe as much as previously, but still solid double-digit growth, which shows the strength of the business we've really built here and the resilient demand even with reduced sales pressure during those strike periods.

France and the U.K. were not fully able to compensate for the Spanish shortfall in the U.K. because the numbers are overall still quite small and in France because we are currently going through a planned restructuring, which has resulted in reduced field presence. The restructuring has the goal to accelerate our growth in France and ideally turn the country into the next Spain, and the measures are progressing well. What's worth mentioning also in France is an important win with AP-HP. AP-HP is a network of 38 university hospitals in and around Paris, where our pharmaceutical Sedaconda (isoflurane) has so far been blocked.

So until now, these hospitals -- and again, we're talking about 38 university hospitals, so big potential could either not use inhaled sedation at all. That was actually most of them or only with sevoflurane. And as you probably remember, since the SESAR trial, we've seen a decline in sevoflurane accounts, especially in France and generally a shift away from sevoflurane to isoflurane. So now these hospitals are open for business for us, which is a tremendous growth opportunity for our French team.

With Germany being a bit weak in Q1, these countries now represented more than 40% of our core business, so excluding the contract manufacturing business, which is a huge shift compared to the situation only a few years ago where we essentially had Germany and nothing else. So even with a slower growth quarter like this one, the development in our other direct markets remains a great success story.

Positive development also in our distributor business on Page 9, with 23% growth. We've laid a lot of groundwork last year with a much stronger focus on key partners and also a cleanup, I would say, among low-performing partners. This is now showing results. Our prioritized partners are performing well, and we also see good growth in Saudi Arabia, where we have been awarded a tender last year. You know that the sales in that business are a bit more volatile than in our direct markets. But with these achievements, I'm expecting solid growth for the full year as well.

Then let's go to the next page and switch gears to the United States. As you know, the U.S. is our largest growth opportunity that becomes very, very visible when you compare the addressable market in the direct markets where we operate today with the addressable market in the U.S. We have estimated the U.S. market potential for our products to be around SEK 10 billion to SEK 12 billion, which is 3x the European potential of our direct markets today. So in other words, the day we will hopefully receive approval in the U.S., our addressable market would instantly quadruple.

The higher potential in the U.S. is because of a high number of ventilator beds, a different medical practice that favors intubation and mechanical ventilation more than in Europe and also an overall higher price level, even though we have not yet built in higher prices into that addressable market number here. So that may represent additional upside.

Let's go to Page 12, please. It goes without saying that we are very convinced of the benefits of inhaled sedation that we have seen over many years in hundred thousands of patients. So it will be very, very exciting to bring this therapy to the U.S. when it comes to the right launch approach, we continue to believe that we can create the most value if we launch ourselves in the U.S., capture more of the upside, generate proof that this therapy can be successful in the U.S. and make money in the U.S. while maybe over time, keeping the option open to complement our presence with a partnership if we deem that to create even more value.

This strategy will create the most value because the large addressable market that I've been talking about is quite concentrated with less than 5,000 hospitals in the U.S. that have intensive care units and the number of high potential hospitals is much smaller than that. So we can go for a relatively targeted launch approach, building around the great network of KOLs and supporters that we already have in place, thanks to our clinical trials.

We also see a very good product market fit, for example, of the proven opioid reduction that our therapy has shown to provide in all of our studies so far, for example, because a reduction in the ICU length of stay is generally an effective driver of adoption in the U.S. and also, for example, because the guiding thought behind existing treatment guidelines that they have in the U.S. So things like fast wake-up, early mobilization, early ICU discharge are quite in line with some of the characteristics of inhaled sedation with isoflurane. So lots of excitement about the U.S. with the submission coming up very soon.

So let me hand over to Peter to take us through our progress in the U.S.

Thank you, Johannes. So our preparations for NDA submission are on track. We have our 2 U.S. pivotal studies that showed that the primary endpoint was met, and we did not see any new -- there were no new safety signals in any of these trials. And based on the timing of the study, we expect a good level of differentiation with our primary and key secondary endpoints and also the pharmacokinetic and pharmacodynamic profile of isoflurane. As you know, we have a Fast Track Designation with the FDA, and we had a successful pre-NDA meeting with the FDA in the end of 2025. We have the Early Access Program that is ongoing, and we are expecting to submit our NDA to the FDA in the middle of this year. And the standard review time after 2-month validation is 10 months. In the case of priority review, it's 6 months.

There are also medical affairs activities ongoing in the U.S. where some are driven by investigators. For example, we have only this spring, we have 3 inhaled sedation reviews published by 2 by trial investigators and 1 by an institution that was not part of our trial with a positive view on inhaled sedation and sort of preparing the market and it is completely independent from us. We also have investigators from the U.S. trials presenting at major congresses, both in Europe at the ISICEM Congress in Brussels, and Jeremy Beitler presented inhaled sedation and the U.S. preliminary data. And we have also investigators presenting at the Society of Critical Care Anesthesiologists in Montreal, early May and at the American Thoracic Society in mid-May in Orlando.

We're planning to organize a clinical Scientific Advisory Board in Q3, and this will be focusing on target population, patient categories where inhaled sedation is considered to bring -- provide most value. We'll also be looking at the science -- available science, the current data and discussing with advisers about what's available and what might be additional research that they consider to be relevant. And we'll also be discussing implementation and training such as education curriculums and continuing medical education activities to include when inhaled sedation is launched in the U.S.

And if we move to the next slide, Slide 13. So looking at the trial results, our secondary endpoints showed some benefits. And the most important one is our first key secondary endpoint, where we found that there was a greater opioid reduction with isoflurane in both our trials. And this was also confirmed in our European trials, both the Sedaconda study and the IsoCOMFORT study showed the same pattern of opioid reduction. There is a pharmacological explanation to this.

The consequence of reduced opioids is that dose-dependent side effects can be expected to be reduced side effects such as constipation, respiratory depression, iatrogenic withdrawal syndrome, delirium, also interestingly, a large U.S. cohort studies demonstrated that the opioid dose during mechanical ventilation, the very measure we showed reduction with isoflurane, that dose is -- correlates with the likelihood of development of persistent opioid use in the year after ICU discharge in nonsurgical patients. So that makes an opioid reduction even more attractive in the U.S.

The studies demonstrated also fast return to wakefulness. Almost 80% of patients receiving isoflurane were awake within 60 minutes after the end of treatment. And we know that with IV sedation, especially after deep and prolonged IV sedation, long and unpredictable wake up times are common. And this implies -- impedes the workflow in the ICU, a long time to wait to be able to do neurological assessments or to extubate patients. It leads to patients having to go for CT scans to investigate if there's anything else than sedation that lies behind poor wakefulness. And so this is also a unique aspect of isoflurane, which is rapidly eliminated by the airways.

We did see some nonstatistical trends that are reassuring and potentially beneficial for uptake in the U.S. So for example, numerically lower mortality in both the 2 U.S. studies despite this being a novel potent therapy. Investigators use this and in both studies, we're talking about 4% to 5% lower mortality, 30-day mortality in the 2 trials. And then we have some other potential benefits. And all of these things are nonstatistically significant will be subject to discussion with the FDA if they merit placement in the label, but we saw on average 1 ICU-free day more with isoflurane in the U.S. trials together with our European trial and also the U.S. trial alone. And this, of course, is one ICU-free day more means a lot for patients, for families and also for health care in terms of work and cost.

The pharmacological features of isoflurane imply that there's minimal metabolism that elimination is via the airways and completely independent of renal and hepatic function. And those are functions that are impaired in somewhere between 1/3 and 50% of mechanically ventilated ICU patients. So the features alone of the therapy explain a lot of the benefits that we are seeing in our trials that will be unique the day we launch.

And on the next slide, Slide 14, we can see the U.S. map, where you see the trial sites from the INSPiRE-ICU studies. We have interacted with many of these investigators still. Some are in the Expanded Access Program and some are advisers or part of advisory board ahead. And there is interest and looking forward to the time that inhaled sedation will be launched. Many of them clearly wanted to speak about inhaled sedation and that, of course, will be possible the day we launch.

If we move to the next slide, Slide 15. As Johannes mentioned, our Early Access Program has started and the Early Access Program is FDA granted us the possibility to give away our products to hospitals that are struggling with difficult sedated patients when intravenous sedation fails or when there are significant risks with IV sedation for the patient. And this EAP is open to all interested hospitals in the U.S. And besides helping these patients that are struggling and that at risk of adverse events, the Early Access Program brings value because it includes the use in a broad range of conditions, including such that were not studied in our trial, for example, patients on heart-lung machine, on ECMO, just one example.

It implies that inhaled sedation, the practice, the experience that has been gained in the trial sites will not be lost and that is, of course, an advantage the day the therapy will be launched. There will be units that have proficiency and expertise that we can leverage at launch. And for us, it's also an opportunity to practice all the aspects of implementing the therapy in a U.S. hospital. And currently, we have 9 hospitals that are interested in the EAP. So we're adding on new hospitals. Currently, we have Vanderbilt University Hospital that has treated the first patient, and we have 2 more hospitals that are going live as we speak.

We move over to the next slide from there. So that's Slide 16. And here, I hand over to Johan.

Thank you, Peter. Yes. So if we switch focus to our financial results for the quarter, starting with net sales, and Johannes has already discussed these aspects here, but just to reiterate the main points. So our net sales for the quarter was SEK 53.4 million. That's 7% down relative to the same period last year or 2% lower if we look at it in constant exchange rates. And as Johannes described, sales decreased in Germany, 15% excluding exchange rates, largely driven by the low ICU occupancy rates that we saw during the period.

Other direct markets saw some growth, 7% at constant exchange rates, which is good, but we've seen higher growth rates in recent quarters. Johannes described the dynamics there as well. Despite the strike in Spain, there is still a good growth contribution from that market in these numbers.

On the distributor market side, sales increased by 23% at constant exchange rates. And we saw contract manufacturing sales of SEK 2.7 million for the quarter, which is quite an increase compared to the same period of last year. That's mainly due to timing effects in the comparator period of last year, phasing effects during the year 2025 essentially. If we look at gross profit, we report SEK 37.8 million for the quarter. That's down slightly from SEK 40.7 million in the same period last year. But importantly, as Johannes also pointed out already, the gross margin remains stable at 71% for the quarter.

What we see here is still that we have a positive effect from the reduced cost of goods for our main product, the Sedaconda ACD. That's a result of the acquisition and was essentially one of the key rationales behind the acquisition of our supplier in Malaysia. And -- but in Q1 this year, this was offset by the mix effect of having a relatively large share of contract manufacturing sales and also, to some extent, distributor sales in the overall sales mix for us.

So the -- for example, the contract manufacturing part of sales was 5% in Q1 of this year compared to only 3% in the comparator period. EBITDA for Q1 2026, SEK 1.8 million. So positive group EBITDA, 3% group EBITDA margin, ex-U.S. EBITDA for the same period, SEK 5.1 million, also an improvement to 10% margin -- EBITDA ex-U.S. What we see is that we are able to continue to reduce our OpEx. So in this period, Q1 2026, it came in at SEK 43 million, which is down from SEK 46 million in the same period of 2025.

And this is really a proof that we are able to continue to find efficiencies in the organization and really limit cost increases that you would be expecting given the fact that we are growing sales, but we're able to really contain costs in a good way, which enable us to show this improving EBITDA while having these market headwinds that Johannes has described in the first quarter of this year.

At the bottom of this slide, you can see how our organization has developed. So at the end of Q1 2026, we had 130 colleagues in the Sedana Medical Group compared to 126 at the end of Q1. So this includes both regular employees, part-time factory operators in Malaysia and also consultants. So I think what's also important to note when we think about the cost savings that we're able to do in the organization is if we exclude Innovatif Cekal, our contract manufacturing or our manufacturing site in Malaysia and look just at the organization, excluding those colleagues, we see that the number of employees and consultants at the end of Q1 2026 was 80 compared to 86 at the end of the same quarter of last year. So there, you can see the way that we've further streamlined the organization, in particular, in the sense of a leaner headquarter over the past year.

On the next slide, we have our cash flow and available funds. So cash at the end of the quarter was SEK 81 million compared to SEK 91 million at the start of the year. And the change in cash here, as you can see, is negative SEK 10 million, and that's really mainly driven by investments in intangible assets of SEK 13 million, which is in turn, mainly U.S. related as we prepare for the NDA submission at midyear. Cash flow from operations during the quarter, positive SEK 3 million compared to positive SEK 6 million in the same quarter of last year. So I continue to see a positive cash flow from operations. The reason why it's slightly lower than the comparator period is mainly due to increased inventory.

Cash flow from investing activities in Q1 2026 of minus SEK 14 million, down slightly from minus SEK 17 million in the same period of last year. And again, this is driven by U.S. CapEx related to the NDA submission preparations. So total cash flow for the quarter of minus SEK 12 million, same level as the first quarter of last year. And we expect CapEx to remain at the new and lower level over the coming year. And really, once we're through the FDA review period, we expect really quite limited R&D-related CapEx beyond that period. So we expect to be sufficiently financed to achieve U.S. approval.

And just to point you to the charts briefly on the right-hand side of this slide, where you can really see how the reduced cash burn that we've seen in recent quarters has contributed to shoring up the cash position as we now also have reported SEK 81 million for the end of Q1 2026.

On the next slide, as usual, you can see our main shareholders at the end of the period. We remain thankful for the support that you provide. And we've also noted an increased holding by a few of the largest shareholders in recent months, which is, of course, very appreciated. And also, I'd just like to add that this is my last quarterly earnings call as CFO of Sedana Medical. So I would like to take this opportunity to thank all our investors and analysts for great conversations and interactions over these past several years. So thank you and look forward to staying in touch in the future.

And with that, I will hand the word back to Johannes.

Yes. Thank you, Johan. So on that last point, we will have Johan around until approximately mid-June. His successor is already gearing up to take office around that same period of time. And of course, before that, we will ensure a smooth and successful handover.

But now to wrap up this presentation before we head up -- open it up for questions, and we look at the last page, I see 3 big reasons to believe in Sedana Medical's success. Number one and the foundation of it all is a therapy that makes a difference for critically ill patients every single day. We help them wake up faster, recover faster, communicate with their families earlier and leave the intensive care unit earlier eventually and with several hundred thousands of patients in more than 1,000 hospitals around the world treated and more than 1 million sedation days under our belts, we can safely say with some confidence that we are living up to our purpose of improving life during and beyond sedation.

And every ICU patient has a life that is worth getting back to and no one should be in the ICU longer than necessary. So true patient benefit and cost saving for the hospital as well. Number two, we have a growing and profitable core business in Europe and now even showed positive EBITDA on a group level in Q1. This provides proof of concept that we can make money with this therapy and of course, a stable platform for the U.S. launch as we had aimed for all along.

And number three, we're now getting closer and closer to the U.S., which one day should become our largest market as we would quadruple our addressable market upon U.S. approval. And with 2 successful U.S. studies that Peter has talked about, the Fast Track Designation from FDA, the Early Access Program that is underway, there is a lot of positive indicators. So we are hoping that inhaled sedation with isoflurane will benefit also U.S. patients as an approved therapy in the very near future.

With that, thank you very much for listening, and we will now open it up for your questions.

[Operator Instructions]

But now we can start with you, Johannes, Johan and Peter and all the written questions that you received.

Okay. So let's go through those.

So we got a question from Scott Wright. So Scott, thanks for submitting that question. It says, what are Sedana Medical's key growth drivers and strategic priorities for Q1 2026.

I can see this question was submitted in the first minute of the call. So I'm hoping that the call has answered those questions already, but maybe in very brief sales performance, difficult quarter in Germany with the sales decline because of less patients in the ICU, lower growth than usual in other direct markets due to the strike in Spain. And on the other hand, a strong quarter in both distributors and contract manufacturing, overall a 2% decline.

But what's really standing out, I think, about this report is that nevertheless, we delivered a positive EBITDA on group level. And in terms of priorities, we are big believers of focus. So we are focused on 3 priorities always. One is sales growth. The second one is getting to profitability and the third one is getting to the U.S. And over the last years, as you've seen in the call, we've made very good progress across all these priorities.

Then I will move to the questions from Mattias. Thanks, Mattias, for submitting those. The first one, I'll hand over to Peter. Keen to hear any feedback from professionals at Vanderbilt University so far.

So we do not have any formal feedback in terms of protocol or results from the patients, but only before the Expand Access Program, they were very enthusiastic about using inhaled sedation in this very patient group. So the feedback has been positive.

All right. I'll move on to the next. What -- how long does it take to reap the benefits of the initiatives you are taking in France and the U.K.

So we are making interventions at different levels. One is kind of across all of our countries with new sales leadership, intensified sales training a refresher on how to ensure we focus our activities on high potential accounts and don't spend too much time on lower potential accounts and so forth. All of that is being implemented while at the same time, we're also making structural changes, for example, in France. And the beauty about sales is that you can see the effect of these things relatively quickly, meaning after a few months, you know whether things are working or they're not working. So I'm very optimistic about especially the second half of this year.

Again, there's a bit of an imbalance in how last year has looked from a sales perspective with a very, very strong first half last year, which we're now up against as a comparator and then a weaker second half. So in the second half, with all the things we put in place and a more realistic comparator, I think we will see numbers that are closer to what we're used to.

So then there's another question from Mattias. What would you -- would you perceive the Q2 comparator quarter in Germany as even more difficult to face? I would guess that the high number of admissions in Q1 2025 helped sales for Sedana in Q2 with a lag.

Yes, that is true. So there's a lag of a couple of weeks in between what we see in the ICU in terms of patient numbers and the orders. The quarter 2 last year in Germany was the strongest one from a sales growth perspective. So we grew 19% in that quarter. So we are again up against a tough comparator in Q2. But then similarly to what I said on the company level, we, in the second half are facing an easier comparator, I would say, the difference between the 2 halves of the year in Germany was even more pronounced than on a company level. So on a company level, first half was 15% higher than the second half in Germany, that same number was 19%. So 19% higher sales in Q1 than -- sorry, in the first half than in the second half, which is a quite unusual pattern. So yes, Q2, a tough comparator, but after that, it's going to get better.

And then there's an additional question from Mattias. One additional ICU-free day shown as potential benefit. Why is that? Is it something you can do to prove inhaled sedation -- to prove inhaled sedation is numerically favored by 1 day over standard of care?

So if you talk to customers that have been using our therapy, I think what they will tell you is that all these benefits go hand-in-hand. So patients wake up faster, they are extubated faster, they recover better and faster, and that then eventually leads to them also leaving the ICU earlier. And based on our European trial, we had our post-hoc analysis showing a 3.5-day difference. And now in the U.S. studies, we also saw a consistently better ICU-free days for isoflurane compared to propofol, but we found 1 day difference. And the difference here that is important to note between the studies is in the German study, the European study, doctors were allowed to leave patients on isoflurane beyond the 48 hours of study duration.

So we had patients that were on isoflurane for the full length of sedation and we had patients that were on propofol for the same period of time. So we were comparing apples with apples essentially, and that gave us a 3.5-day difference. In the U.S., the way the study was agreed with the FDA, everybody was switched back to propofol after 48 hours. So essentially, we are comparing one group that was on propofol throughout with a group that was on isoflurane for maximum 48 hours and then propofol afterwards. So that naturally leads to a smaller difference, but I still think intuitively, it's quite impressive that with a change of the sedative for 48 hours maximum and everything else being equal, you still get these patients out of the ICU for a day earlier on average.

So that, I think, is going to be a key element of how we will be commercializing this drug, not necessarily to the clinical stakeholders only, but also to the purchasing groups and the more administrative parts of the hospitals.

Then there is a question from Johnny. What is the estimated total cost of the Early Access Program? So we've not disclosed exactly what that would cost. The way to think about it is we are supplying the products free of charge. So these are not commercial sales, but we are providing them for free. Of course, not -- the cost to us is, of course, much lower than it would be to a customer because we only book the cost of goods. So the more patients we have in the program, the more expensive it will become. But in the grand scheme of things, it's not going to move the needle too much.

But at the same time, as Peter was describing, it's a very effective way for us to get hospitals up and running before the actual approval. It's a way for us to test our processes. It's a way for us to find our way around internal -- hospital internal processes and so forth. So it's a well-made investment from that perspective, I think, even though we don't disclose the exact amounts.

Then there's another question from Peterson. Thank you for that as well. How do you see your pricing possibilities in the U.S. if approved?

Nice to see the great savings with Sedana therapy, but not so conclusive in the trials. So there's kind of a general and a more specific answer to that. Generally, what you see in the U.S. is that the medical device prices are quite a bit higher than in Europe for different reasons. Differences can be different in different segments of the market. But if you look at sedation therapies, for example, sometimes the U.S. pays double or sometimes even triple of what is the case in Europe, that's no guarantee that we will see the same for our therapy, of course. But I think the way to think about it is if -- even if we can only talk about one only "1 day, 1 additional ICU-free day." An ICU day in the U.S. costs between $5,000 and $11,000 depending on the exact care setting.

So there is a significant saving by using our therapy. As a reminder, the NICE, National Institute for Health and Care Excellence in the U.K. has confirmed a health economic benefit of GBP 3,800 compared to using intravenous sedation and that is per patient. So also a quite significant savings, so quite in line with potentially an even higher saving in the U.S. because everything is more expensive in the U.S. So that will be a very powerful argument, especially since in the U.S., hospitals are much more effective in understanding the P&L impact of introduction of a new therapy on their own P&L. So they're much more trained to look for differences in length of stay.

Those were the questions that I have received through the chat here, but I also see that there's a hand raised on the phone as well.

Yes, there is a number ending with 771. Please introduce yourself.

This is Filip from Pareto. So I just had a few questions today, but I'll take them one by one. So firstly, perhaps on the strikes in Spain. So if you could elaborate a little bit, has that mainly affected the usage of the device to -- you talked about this minimum capacity. So I guess that means fewer patients during the quarter. So is it mainly that? Or is it more the ability to further penetrate the market with sales activities that have been -- have had the highest impact?

Yes. Filip, thanks for the question. That -- it's a combination of both. So this is a nationwide strike across all specialties. So it's not ICU specific. It's doctors in Spain complaining about working conditions, 24-hour shifts, the pay, of course, and so forth. And I think if you follow the news a little bit, I think this must be probably the largest strike in health care that Spain has seen in a long time, and there's talk about, I think, 1.5 million medical appointments that have not happened that should have happened because of that strike and so forth.

So overall, big impact on the country. The way it affects us in these weeks, so again, 1 week every month where they're out of business, it's, of course, patients are still being treated in the ICU, but at like -- at a reduced capacity. So less patients overall. So unless it's totally necessary, people will not be in the ICU. And the main impact for us is that our salespeople cannot do their daily job. So there's no doctors to talk to during that week. You cannot come for trainings because there's no time for that. If you're starting up accounts, there's no way to follow up and be with the teams to help them treat patients because overall, just the access is very, very restricted. So it's both less patients, but also mostly the access that is the problem for us. But again, despite that, I mean, we have essentially Spain was on strike for 1 in 4 weeks every month, right?

So 25% or so of the time was not effective in that sense for us. And still, we were able to deliver growth, which I think is also -- there's a very positive message in that as well. Now of course, we're hoping that these strikes will be over quickly, the way it looks right now, it's more likely that it will take some time because the demands and what the government is ready to offer is still very far apart.

Okay. Yes, that makes very good sense. So the kind of limited ability to like get back to growth in Q2 as well? Or do you see it could go into Q3, Q4 as well or...

Well, now this is pure speculation. Q2, probably we will see a similar situation also because these -- the weeks have already been scheduled. So the doctors already know when they will be on strike. So recommendation is not to get sick while on vacation in Spain. At some point, I guess, one of the parties has to move and the comments -- like the comments you get from people who are closer to this than I am is that since doctors get less money during the strike weeks, at some point, the demand will have to become more realistic from a perspective of what the government can meet. So probably we will see the same in Q2 and then Q3 will hopefully be solution mode more than strike mode. But again, speculation because I can't look into the future.

Then just a question on the gross margin. So 71%, which is in line with last year and then back at levels that you had before the acquisition. So you covered the reasons, the product mix, but can you say what the gross margin would have been if you would have had the same mix as last year?

Well, we typically don't provide that type of granularity on the gross margin. But I think one guidance that perhaps could be useful to you as an analyst would be to say that the contract manufacturing margin that we have is roughly half of what we have for our core business. So then, of course, if we have 1 quarter such as Q1 2026, where the contract manufacturing accounted for 5% of total sales instead of like last year, 3%. Of course, that has a bit of an overall headwind for the gross margin.

All right. Then perhaps another question to you, Johan. I don't know if you want to answer this, but the increase in inventories, you talked about that a little bit, and I saw it in the report as well. So are there any like specific effects of this? Are you increasing the inventory ahead of the U.S. launch? Or is it to have some buffer for potential supply disruptions with everything that's going on at the moment?

Yes. So it's 2 things really. One thing is that, as you know, we are continuously working with trying to find improved efficiencies and lower prices in our supply chain. When you make changes there temporarily, you might need to increase your inventory to have a bit more buffer when, say, you -- basically, you make changes to the supply chain essentially. So that's part of it. And then another part is actually that when we were in negotiations with our supplier in Malaysia leading up to the acquisition, we draw down inventories that we are now replenishing to some extent at this point. So it's not yet any inventory buildup ahead of the U.S. So it's more sort of temporary corrections.

Great. And then I think the last question that I have around potential publications from the results, the U.S. results. Are you expecting any sort of publications in the near term?

Yes, I can answer that. So not in the near term, but they are in the process of being submitted for publication. That, of course, is a little bit unpredictable depending on sort of the impact level you aim for and review time, et cetera. But we do definitely expect to see them published well before launch.

So there are no more questions at this time. So I give the word to you for some closing remarks.

Yes. Thank you very much for listening. Thank you very much for the good questions and discussions, and I wish you a nice afternoon.

Hello, and welcome to today's FinWire broadcast presentation with Sedana Medical. [Operator Instructions]

With that said, I'll hand the floor to you. Please go ahead.

Thank you for the introduction, and a warm welcome to our Q4 and full year report 2025. This report stands out for me in a very positive way because we delivered on an ambitious goal that we set for ourselves.

Coming out of the COVID-19 pandemic and being faced with a sharp revenue decline and the biggest loss in Sedana Medical's history in 2022, we committed to the goal to reach profitability in our core business before we launch inhaled sedation in the U.S., because we believe that it was essential to build our U.S. expansion on a stable, cash-generating platform to demonstrate proof-of-concept, but also to help finance the launch investments in the U.S.

Now a few years later, I'm proud to say that we have delivered on that ambition, and we have reached a positive EBITDA in our ex-U.S. business for the full year 2025. This is the first time for Sedana Medical in its history as a listed company.

So let's jump into the slides on Page 3, which shows our progress in our 3 priority areas: sales growth; profitability; and the U.S. On the sales side, we've ended the year at SEK 200 million, which represents a year-over-year growth of 16%, excluding exchange rate effects. 12% out of this 16% was organic and the remaining 4% stemmed from our contract manufacturing business in Malaysia. This marks an all-time high in sales for the full year and also our Q4 numbers are the highest we've ever had with SEK 52 million.

On the profitability side, as I already said, we are proud to report a positive EBITDA ex-U.S. for the year of 3% and 8% for the quarter. And also on the Group level, we've improved our EBITDA by 12 percentage points for the year, which is very good to see and even had a slightly positive Group level EBITDA in Q4, amounting to 0.1%.

Also, the gross margin looked good in Q4 with 73% as we now see the cost of goods improvement in our main device come through as a consequence of the acquisition of our supplier in Malaysia. And the end of year cash balance was SEK 91 million.

If we look at our progress in the U.S., the big achievement for the year 2025 is that we have made several important advances to reduce the risk associated with U.S. approval. Both our pivotal trials met their primary endpoint and showed no new safety findings, and also the secondary endpoints offer several potential ways to reach differentiation, both in terms of clinical benefits and also on the health economic side for hospitals.

We were also encouraged by the FDA authorizing an early access program, which allows us to treat patients even ahead of the official marketing authorization. And we also had a very positive pre-NDA meeting with the FDA in Q4, during which the FDA confirmed that the efficacy and safety data that we have collected appear appropriate to submit the NDA, which we're now working towards and as previously communicated, expect to complete midyear.

The next page shows all the work we have done over the last year's condensed in only one picture. You can see how sales dropped after COVID and in line with that, the EBITDA loss 2022 grew to SEK 83 million. And as a reaction, we started a turnaround program in which we have really fundamentally changed how we invest our money. We have made significant cuts in everything that is noncustomer-facing and administrative in nature.

Just to give you an idea, our Swedish headquarter operates with less than half of the people today. And part of that freed up cash we have then reinvested into strengthening the frontline team. So we are much more focused on commercial execution today. We are much more customer-centric company, and we have more people in the field.

But also here in the field, we have applied a very disciplined and differentiated investment approach where we increased spend in countries that are meeting our profitability targets and show good growth momentum, but we also cut back fairly rigorously where that is not yet the case.

And this slide summarizes quite nicely the results. This year, for the first time, we show a positive ex-U.S. EBITDA for the full year. And also on the Group level, we have consistently seen good improvements. And if you compare the pace of sales growth with the pace of bottom-line improvement, it also shows that every single year we have done more with less, so growing sales while simultaneously reducing the cost.

If we then go to the next page, Page 4, with this very positive outcome, we've also met our financial target for the year. We guided for low to mid-single-digit positive EBITDA ex-U.S. We landed on 3%. There was some exchange rate headwinds during the year to our P&L. And without those, it would have been 4%. And based on that, we have updated our guidance now for this year. When it comes to ex-U.S. EBITDA, we will continue to grow that and expect to deliver positive EBITDA in the mid to high single-digit range now. And also on the Group level, we anticipate further improvement and actually get closer to breakeven for the full year.

What could potentially affect that Group level target is a potential acceleration of the upcoming FDA review. So if we were to get priority review, for instance, then it becomes clear that the launch in the U.S. may happen earlier, then we will, of course, also start building up in the U.S. earlier, which may then impact the Group level target. If that happens, would, of course, clearly be a luxury problem to have.

Then let's look at the sales performance per region on the next page. Thank you. The strongest growth we have once again seen in our other direct markets, so our direct markets outside Germany, which delivered 32% growth for the full year and 31% growth in the quarter, both numbers excluding exchange rate effects. The growth was once again led by our Spanish team, which has shown really fantastic growth for the last years and has actually quintupled sales since 2022. That was again the case in Q4 based on a very strong execution, but also based on a strong network of believers and opinion leaders in the customer side.

And what has worked really well in Spain is that we do not just have the academic key opinion leaders who are oftentimes not treating so many patients anymore, but we have a lot of what we call bedside ambassadors. So oftentimes younger doctors who treat a lot of patients, see the benefits of inhaled sedation in real-life, and not just in studies and who are at the same time very, very influential for their peers. So other doctors who seek advice on the best treatment options.

And what the Spanish success story really also demonstrates is that very focused approach targeted at establishing inhaled sedation as a standard therapy in select high potential hospitals and then building from there is the most effective way to reach rapidly increasing adoption. And that's a model that we are trying to replicate in other geographies, of course, as well.

In the U.K., we were unfortunately hit by a temporary staff absence during part of 2025, which in a small team leads to quite significant reduction in field presence. So we could not continue on the strong growth path that we had just seen the year before, but instead had a rather flat development. What happened here besides the staff absence was something you often see when you have reduced resources, but still have a lot of incoming demand from potential new customers. You run into the problem that a lot of time is taken up by responding to potential new customer requests and you neglect a little bit to maintain and nurture and drive the growth in your existing customers or customers that you've just opened the year before.

And we've suffered a bit from this phenomenon in 2025, but now have the team fully staffed again and are also focusing our energy on the right balance again between new customers and existing customers. What's also helping a bit in the U.K. is the MHRA has now approved our pediatric indication as well, which provides some upside as well. So -- And Q4 already looked better than the previous quarters, and we saw some good solid growth again.

In France, we continue to see a quite split performance with isoflurane customers performing very well, but in customers that are still using our device with off-label sevoflurane, we continue to see sales decline following the SESAR study. Overall, this has resulted in a almost flat development for the full year, which is obviously not good enough. So the plan for France is quite self-evident, focused on switching remaining sevoflurane users to isoflurane and focusing on commercial execution, of course. And there, we are making good progress.

If you look at the SESAR clinical trial sites, which you would imagine are the hardest nuts to crack given the SESAR results, more than 60% of those hospitals are today using isoflurane. So the conversion is progressing well, and I'm hoping for a good year 2026.

Overall, I see our other direct markets, obviously, as big success stories. Only a few years ago, Sedana Medical was essentially Germany and not much else, but now we've really built a business in these countries that represents 35% of our core business sales already, and we will see that share continue to grow with Spain continuing on a strong trend, and U.K. and France finding their way back to strong growth over time.

Then we move to Page 7, please, and have a look at our largest market, Germany. Here, we have a very mixed picture for 2025. It's almost like we had 2 completely different halves of the year. The first half was great with 13% growth in local currency, and we were very happy that the sales acceleration plan we had implemented was showing good impact. But then the picture in the second half looked very different with a sales decline of 7% in local currency. And in Q4, it was minus 6%, as you see on the slide.

So what has happened here? We are always fully focused on what we can control, which is commercial execution and look for ways we can improve that. But the truth is we did not do things massively different in the second half. The team is fully staffed and is executing according to plan. But what you will see on the next page in just a second is that we had very different levels of ICU occupancy during the 2 halves of the year with considerably less patients in the second half, which has impacted our performance.

Now it's tempting to simply blame the performance on external factors outside our control and simply trust that the markets will swing in our favor again. But for us, that's, of course, not good enough. So we have to accept that sometimes the market goes against us, sometimes it will go for us. But for us, that's even more reason to double down on commercial execution, maximize time in the field, be very sharp in our targeting where we spend our time and be as impactful in every single customer interaction as we can be.

And one thing, for instance, we can actively work on is to improve our penetration in patient groups that are less subject to seasonal swings than respiratory patients. So for example, neurocritical patients, surgery patients or cardiac arrest patients, you see less of these seasonal swings compared to the respiratory patients.

And with 14% penetration in Germany, we still have lots of places to grow. So the customers we have today represent a bit more than half of German hospitals with ICUs. But since we focus on the high potential accounts, 70% of all ventilator beds in Germany are represented by our customers. So that also shows you where the focus has to be. The biggest opportunity lies in increasing penetration in existing accounts, while simultaneously opening a few high potential accounts where we are not yet present.

On the next page, Page 8, you see what I've already been touching on. So this is data from the Robert Koch Institute in Germany based on a representative sample of 67 Sentinel hospitals and shows the development of the weekly number of patients with severe acute respiratory infections that did require intensive care.

It's not perfect data as it's -- there are other patients in the ICU as well and the fact that they are in intensive care unit does not necessarily mean that they were incubated and sedated. But these are the majority of patients in the ICU, especially this time of the year. And therefore, this is a fairly good indicator of how our relevant market is developing.

And what you can see here is the typical seasonal pattern with more patients in the ICU during the winter months and less during the summer months, but you also clearly see the differences between the seasonal patterns in 2024 and 2025. So between January and end of April, beginning of May 2025, we had a long and quite strong flu season in Germany. And that time, we had 12% more respiratory ICU patients than the year before. But then it flipped. And between May and December, with the exception of, as you can see, maybe 2 weeks, we had considerably less respiratory patients in German ICUs, 25% less over that period, which is obviously very significant.

And now again, in the first half, we grew 13% because usage in the hospitals were high and then reorders usually come earlier and also customers tend to order more. But when the usage then declined from May with less patients, hospitals were still working down their inventories built in the first half and orders came later and tend to be smaller. So that's why we saw that sales decline in the second half of the year.

Now we will have these swings from time to time. But as I said before, it should not distract ourselves from keeping the focus on what we can control.

Then let's move on to Page 9 and look at the distributor business. At first glance, it looks like a rather boring year with 4% growth. But during this year, we have done a lot of good work under new leadership for that business that will lay the foundation for future growth. We are now much more clear where to focus, and which key partners to really support, and how we are much more professional in the performance dialogues with our partners and also hold lower performing partners much more accountable. So for example, we terminated also contracts with 5 distributors during the year that were not meaningfully distributing, to be more focused.

So with that, sharpened focused, I'm looking forward to a hopefully successful 2026 in that business. And Q4 was already promising with a strong 44% growth versus the year before.

Let's go to Page 10 and switch gears to the United States. As you know, the U.S. is our largest growth opportunity. That becomes very evident when you compare the addressable market in the direct markets where we operate today with the addressable market in the U.S. We have estimated the U.S. market potential for our products to SEK 10 billion to SEK 12 billion, which is 3 times the European potential today.

So in other words, the day we will hopefully receive approval in the United States, our addressable market would instantly quadruple, and the higher potential in the U.S. is because of a high number of ventilator beds, a different medical practice that favors intubation, and mechanical ventilation more than in Europe and also an overall higher price level, even though we have not yet built that into the numbers here.

Let's go to the next page, Page 11, have a look at the status and the progress we have made during the year. If I compare to where we were going into the year 2025, it becomes very clear that we have taken several very important steps that contribute to reducing the risk associated with the U.S. approval. First and foremost, we received the results of our 2 clinical trials. We met the primary endpoint in both studies in the primary analysis as well as all supplementary and sensitivity analysis. There was no surprising safety findings and also the secondary endpoints came out such that we believe we will have compelling benefits to talk about both on the clinical and the health economic side, all, of course, subject to FDA review.

We are now in the final stretches of completing the dossier, which we are planning to submit midyear, and we are encouraged by the fact that the FDA saw enough value in our therapy to approve Fast Track designation and also authorize an early access program.

We also had a number of important regulatory interactions with the FDA during the year with the highlight being the pre-NDA meeting in the fall. We perceived the agency to be very collaborative, and constructive and helpful in their feedback, and we got confirmation from the agency that the safety and efficacy data we've collected in our studies seem appropriate for submitting the NDA, so we can now proceed towards that, which is, of course, very, very exciting.

And on the next page, Page 12, goes, of course, without saying that we are very convinced of the benefits of inhaled sedation that we have seen over many years in hundred thousands of patients. So it will be very, very exciting to bring this therapy to the U.S. And what this page shows is some of the potential benefits that we hope to be able to use in the U.S. What I have to make very clear, of course, here is that we are not yet approved. We have not even started the review process, which will come later this year. And things like the label we will receive are, of course, fully subject to the FDA's decision.

So what this page shows is things that we see based on our clinical trial results. We did, for instance, show in both trials that our patients had a higher reduction in opioids than that was the case for propofol patients. The reason that matters in the U.S. is that the U.S. is plagued with an addiction epidemic and there is a clear established correlation between how much opioids you receive in the hospital and how much opioids you get discharged, which then leads to the addiction risk. So less opioids in the hospital is a good contributor to avoid addiction.

But there's also very practical problems with opioids in the ICU, such as managing withdrawal and constipation, which you could assume you would see less of with less opioids being used.

What we also saw in the trial is that 75% of our patients were awake within 1 hour of treatment termination, which is in line with what we have in the European label, for example. Now this was not statistically better than propofol in the trial, as propofol patients also woke up fast, but physicians also often perceive long wake-up times in the range of many hours or sometimes days as a big problem in ICU. So fast and reliable wakeup is an important feature for a sedative.

Another important outcome we were very happy about was the mortality numbers. You remember that there was some noise around the SESAR trial last year, where the off-label use of sevoflurane was associated with higher mortality than propofol. Now in the study with isoflurane, so the right drug in our opinion, we did not see any increased mortality. On the contrary, we even saw at least a numerical advantage in favor of isoflurane of 4 and 5 percentage points in both studies, respectively.

Now the studies were not powered to show statistical significance here, but still this is very reassuring results and a clear contrast to sevoflurane results from SESAR.

On the health economic side, hospitals care a lot about the ICU length of stay as a shorter ICU stay in the DRG system means a better profitability on -- of that patient from the hospital's P&L perspective. We did see a higher number of ICU-free days for isoflurane in the European study and in both U.S. studies. On average, that effect is around 1 day based only on the patients that received isoflurane for a maximum 48 hours.

And for launch, when we are discussing with purchasing departments, we will have a full version of these data and for reference, 1 day difference, so saving 1 ICU day corresponds to USD 4,000 to USD 11,000 in the United States system.

It's also well established that isoflurane is eliminated almost exclusively through the lungs and metabolism is minimal. This means that, for example, the kidneys and liver do not get affected as they could be with IV sedatives. And what we see in Europe is that many doctors appreciate that feature and like using isoflurane in renally or hepatically impaired patients, and there are a lot of those patients in your typical intensive care unit, of course.

Next page, Page 13, shows the list of clinical trial sites we had in the clinical studies. You will see many familiar names such as Vanderbilt at Israel; Cleveland Clinic and others. And those centers form our support network for the U.S. already today with many of the key opinion leaders already actively speaking at conferences and working on publications.

Then let's move to Page 14, please, and the Early Access Program. So the FDA authorized an expanded Access Program for us. What that means is that patients who don't have a great alternative today, in our case, because they struggle with IV sedatives, so-called difficult to sedate patients can get access to our therapy already before market approval. And this is great news for patients and caregivers who are struggling with these patients, but it is also good news for us, because by the time of commercial launch, we will already have several hospitals trained and up and running, and we will have gathered a lot of learnings and tested our own processes, which will be beneficial for a successful launch.

We were working towards starting the program in Q4. Now we have moved that to Q1. But since the submission also had moved by a few months as a result of some extra homework from the FDA that we got in the pre-NDA meeting, hospitals will still have a lot of time to benefit from this program before the actual approval.

Let's go to Page 15 to briefly recap our strategic plan for the U.S. As you know, the U.S. is our largest growth opportunity. We've estimated the U.S. market potential for our products to SEK 10 billion to SEK 12 billion. So as I said, the market entry in the U.S. would quadruple our addressable market. We also see a very good product market fit, for example, because of the proven opioid reduction that our therapy has been shown to provide, for example, because a reduction in the ICU length of stay is generally an effective driver of adoption in the U.S., because the guiding thoughts behind existing treatment guidelines of fast wake-up, early mobilization, early ICU discharge are quite in line with some of the characteristics of inhaled sedation that our customers in Europe value already today.

And on top of that, we've already built a network of key opinion leaders in our clinical trial sites. So therefore, we continue to believe that we can create the most value if we launch ourselves in the U.S., capture more of the upside and generate proof-of-concept that this therapy can be successful, while over time, keeping the option open to complement our presence with a partnership if we deem that to create even more value.

Now let me pause here and hand over to Johan to take a more detailed look at our financials.

Thank you, Johannes.

So on Slide 16, you can see our financial results for the quarter in some more detail, and you can also see the positive development that we can show in terms of sales and gross profits over time in the charts to the right here on the slide.

So for the quarter, we reported net sales of SEK 52 million, which is up from SEK 49 million in the same quarter last year. So that's 5% increase in reported currency or 11% increase excluding exchange rate effects.

So we have organic growth, if we exclude our contract manufacturing business of 10%. And as Johannes has described, there is some differences between the core markets that we have. So as described, we see some market headwinds resulting from low ICU occupancy rates in Germany. So Germany decreased 6%, excluding FX for the quarter, while both the other direct markets and the distributor markets grew strongly. So 31% increase from the other direct markets, mainly driven by Spain, as Johannes has described already, and the distributor markets sales increased by 44%, excluding exchange rate effects. So this means that we are seeing a good, positive development also for our gross profit.

So the gross margin improved in Q4 by 3.2 percentage points to 72.7% and that results in a gross profit of SEK 38 million for the quarter. That's up from SEK 34 million in the same quarter last year.

As what we're seeing here, if we look at the gross margin improvement is that it's very much driven by the reduced cost of goods for our main product, the Sedaconda ACD, which follows from the acquisition of our main supplier in Malaysia, which was concluded at the end of 2024. So now in -- Over the course of 2025, we've seen more of that effect come through. And now in Q4 2025, specifically, we see a positive effect of 2.4 percentage points coming from this acquisition of the supplier, out of those 3.2 percentage points increase in total.

If we look at the OpEx, so total OpEx for the quarter of SEK 45 million, which is very much in line with the same quarter last year. So what we are basically seeing is that we continue to find efficiencies in our organization, and we're able to contain cost increases while we are increasing revenue, which is, of course, very encouraging to see.

And this means that EBITDA continues to improve for us. And that's, again, despite the market headwinds that we've seen during the second half of 2025, in particular, in our core market in Germany.

So for Q4 specifically, we report positive EBITDA even at the Group level, so slightly positive at the Group level compared to negative SEK 6 million in the same quarter of last year. And EBITDA for the ex-U.S. business, again, for the quarter is a positive SEK 4 million that can be compared to negative SEK 1 million in Q4 of 2024.

And that means that for the full year 2025, we report Group EBITDA of minus SEK 10 million, which is a clear improvement compared to 2024 when we had minus SEK 31 million. And at the ex-U.S. level, we now report EBITDA for the full year of SEK 6 million compared to negative SEK 17 million in 2024.

So finally, on this slide, and that's also as Johannes has already described, what we have been doing for a number of years now, and that was also very much the case during 2025 is that we are growing the business by reallocating resources to customer-facing functions, while we are streamlining support function and administration functions in the company, in particular, in the headquarter. So that, of course, means that we are shifting also where we see our headcount within the Group.

So at the overall level, it's relatively stable. So slight increase in total headcount during 2025 to 127 from 125 at the start of the year. But if we look at the company, excluding our contract manufacturing, our manufacturing site in Malaysia, we see a decrease in headcount to 77 at the end of 2025 compared to 87 at the start of the year.

So then we can turn to Slide 17, where we show our -- an overview of our cash position and cash flow. So starting with the cash position, at the end of the year 2025, we had SEK 91 million in the bank compared to SEK 112 million at the end of Q3. So this change in cash of SEK 21 million is mainly driven by investments in intangible assets of SEK 11 million during the fourth quarter, and that is mainly related to the U.S. NDA preparations.

Cash flow from operations during Q4 was negative SEK 5 million compared to positive SEK 7 million in the same quarter of last year. And the change there compared to the same period last year is that -- due to the fact that while we have an improving operating income, we have some negative cash flow effects from less interest received during the period and also changes in working capital where we have increased operating receivables and decreased operating liabilities to make that comparison to the same period last year.

Cash flow from investing activities for the quarter, negative SEK 13 million compared to negative SEK 55 million in the fourth quarter of 2024. So what this change reflects is the fact that we are now spending less on U.S. CapEx, again, related to the NDA submission preparations compared to 2024. And also, it should be noted that the comparator period here includes the cash flow related to the acquisition of Innovatif Cekal, which closed in late 2024. So that's negative SEK 25 million in the comparator period.

So that brings us to a total cash flow for the fourth quarter of 2025 of minus SEK 19 million compared to minus SEK 49 million in Q4 of 2024.

So we now expect CapEx to stabilize at this new and lower level over the coming year as we are now, as Johannes has described, in the final stretch before NDA submission, which is expected around the middle of this year, 2026. And we continue to expect to be sufficiently financed to achieve U.S. approval.

And then briefly on Slide 18, you can see our main shareholders as of year-end 2025, and we continue to be grateful for your support.

And with that, I will hand it back over to Johannes.

Yes. Thanks, Johan.

So before we go into the Q&A, let me just briefly wrap it up. I see 3 big reasons to believe in Sedana Medical's success. Number one, and the foundation of it all is a therapy that makes a difference for critically ill patients every day. We help them wake up faster, recover faster, communicate with their families earlier and leave the intensive care unit earlier. And with more than 100,000 patients in more than 1,000 hospitals around the world treated and more than 1 million sedation days under our belt, we can say with some confidence that we are living up to our purpose of improving life during and beyond sedation. And every ICU patient obviously has a life that is worth getting back to and no one should be in the ICU longer than necessary. So true patient benefit and cost savings for the hospital as well.

Number two, we have a growing and now profitable core business mostly in Europe. We've now had all-time highs in quarterly sales in 12 quarters in a row. And as we said in the beginning of the call, we are now at a point where that business is generating positive EBITDA, so provides a proof-of-concept and a stable platform for the future U.S. launch.

And number three, we are getting closer and closer to the U.S., which one day should become our largest market in terms of sales as we would, as I said, quadruple our addressable market upon U.S. approval with 2 successful U.S. studies, FDA Fast Track designation, and then Early Access Program kicking off and a positive pre-NDA meeting. There are a lot of positive good indicators. So we're hoping that inhaled sedation with isoflurane will benefit also U.S. patients in the near future.

So with that, thank you very much for listening up to this point, and we will now open it up for your questions.

Since there is no one on the line for questions, you can go ahead with your written question that you received.

Okay. So you sent those over. Just one second. We've actually got quite a number of questions here. So one is from Mike Ryan.

When do you anticipate full approval and launch in the U.S.?

So the time line is that we will submit the NDA midyear, so mid-2026. What follows then is a 2-month validation period where the FDA essentially checks whether we have ticked all the boxes that we were asked to tick. And this is also the period, for example, where they make a determination of whether we get priority review, yes or no.

So the Fast Track designation allows us to apply for a priority review. And in these 2 months, the FDA will decide whether we will get it or not. Should we get priority review, the review time for that would be 6 months. Should we not get it, the standard review period that applies is 10 months. And then, of course, it's subject to the FDA on how many questions they will come with. But my base case assumption is that we would get approval either early or in the middle of 2027, depending on whether we get a priority review, yes or no.

And then the launch will not be the next day because, for example, the approval will define the label and then there's some production lead time to put the last touches on the launch stock, but relatively soon thereafter. So we are expecting a launch in 2027.

So that was question number one.

Then we had a question, can you talk about intravenous versus inhalation sedation? What's your current penetration in different European markets? And what are the clear benefits that will drive penetration going forward?

So this is one of these markets since we are dealing with mechanically ventilated and sedated patients in ICU setting. It's a quite well-defined niche where there's limited publicly available data available. So it's not like you can buy data that shows Sedana has a penetration of X. But of course, we triangulate our penetration as well as we can in the different markets based on the number of sedation days you have in a country, and we put that in relation to the number of Sedaconda ACDs that we sell because that's a 24-hour device. So it gives us a good idea of how many sedation days our therapy was used.

In Germany, for instance, our 2025 penetration was 14%, so roughly one in 7 patients at any given point in time is sedated with inhaled sedation and 6 are still on IV sedation, which also gives us an idea of there's still -- even in our largest market today, there's still a lot of growth potential.

In the other European markets, the penetration is still a bit lower. But Spain, for example, is one where the trend points towards higher penetration than what we see in Germany today because, for example, indicators like the sales per account shows that an average Spanish customer already has higher sales today than an average German customer because they use the product more broadly in more patient populations.

And that is also to answer the question for how to increase penetration. That is the model that has worked the best for us. So pick high potential accounts, try to establish inhaled sedation as a mainstay therapy, not just as a niche therapy and then grow from there.

Next question comes -- this is anonymous.

The question is, can you talk a bit about competition? Who are your biggest competitors? Dexdor, Precedex in the U.S., midazolam [indiscernible], are they comparable since they are also easy to control?

So the drugs that are relevant on the intravenous side, I would say, is the top 3, propofol, midazolam and dexmedetomidine. What you see very often is that when you ask doctors what they're using, they will always say it's propofol and nobody is using midazolam because those are benzodiazepines with all the downsides that come with it. But when you walk through ICUs, you actually still in a lot of places see a lot of midazolam being used. So it's still around there.

And dexmedetomidine is used mostly for lighter sedation. But what is very typical is anesthesiologists like mixing cocktails. So it's not uncommon that they do not go with only one IV sedative. So it's quite normal for a propofol patient to also have dexmedetomidine mixed in or midazolam mixed in. And then if you have difficult to sedate patients, very easily you have a cocktail of maybe 5 IV drugs, which is one of the big advantages of the gas isoflurane, because you don't need that polypharmacy. So when we switch someone from IV sedatives to inhaled sedation, usually, it's enough to only sedate them with isoflurane.

And in terms of how comparable they are, so in terms of clinical data, we have most evidence versus propofol because our clinical trials have been head-to-head versus propofol. The Sedaconda study in Europe showed that isoflurane patients need less opioids, they woke up faster, there was more spontaneous breathing. So there's clear benefits versus propofol and also easier -- earlier ICU discharge.

There's less evidence versus midazolam, but there is a few older studies that show that those effects are actually more pronounced versus midazolam. So propofol is considered the better drug, if you like, compared to midazolam. And then dex is a little bit -- dexmedetomidine is a bit of a special drug that we use for light sedation. So it's not fully comparable one-to-one.

Let's see if we have more questions. No questions on the line. No, I think then we have answered all the questions.

So with that, thank you very much again. Wishing you a nice day. And handing it back to the moderator.

Yes, so there are no more questions now. So thank you for listening. And bye. Thank you.

Thanks a lot.

Hello, everyone, and welcome to today's Finwire webcast presentation with Sedana Medical. With us presenting today, we have the CEO, Johannes Doll; CFO, Johan Spetz; and CMO, Peter Sackey. We'll do a Q&A after the presentation. [Operator Instructions] And with that said, please go ahead with your presentation.

Thank you for the introduction, and welcome to our Q3 report presentation today. Let's dive straight in on Page 3 with the highlights of the quarter, please. Thank you. The short version of this report is this. If I compare to the analyst expectations ahead of the report, sales have come in lower than expectations, also lower than our own ambitions. But despite that shortfall in sales, our bottom line was actually better than people expected. Year-to-date, we are still showing a profitable ex U.S. business, and I'm very confident that we will deliver on our financial guidance for the full year.

And this is exactly what I am hoping you will take away from today's call. We have now reached a scale and put in place a cost structure that allows us to keep our ex U.S. EBITDA in the positive territory even when we have quarters like this one where market circumstances lead to no or quite low growth, because the truth is this, our business is subject to seasonal swings every year. And sometimes, the seasonal swings differ quite a bit between years. Sometimes this will be in our favor. And from time to time, as we see it today, we will see quarters like this one where we have much less patients with respiratory problems in the ICUs, which will then affect our sales.

What is important for me, though, is that we show consistent growth when we take a bit of a through-cycle perspective and look at longer periods than just 1 quarter. And also that we stay so disciplined on the cost side that lower sales quarters will not affect our goal of achieving positive EBITDA levels outside the U.S.

Looking at the numbers, we grew net sales by 7%, of which 1% was organic and the rest was contributed by our acquired contract manufacturing business. This is quite a difference, obviously, compared to the strong growth in the first half of the year. But despite the low growth, we still stand at 18% growth year-to-date, of which 12% is organic. And again, our ex U.S. EBITDA year-to-date is still positive with 1% and actually would have been 3% without the exchange rate headwinds that we had. So we are fully on track to deliver on our promise to show positive ex U.S. EBITDA for the full year. And with Q4 coming up, which has traditionally been a stronger quarter for us than the summer quarters, I'm quite confident that this will happen.

What we're seeing here is the result of the cost savings measures we have implemented, especially in our noncustomer-facing functions in the corporate headquarters and also the acquisition of our main supplier in Malaysia starting to show positive effects on the gross margin.

On the U.S. side, it's very exciting times now. We are gearing up for the upcoming pre-NDA meeting. Pre-NDA meeting is a formal meeting with the FDA ahead of the submission to create alignment on format and content of the submission, and to ensure we have ticked all the boxes that FDA has asked us to tick. If we receive positive feedback on all our questions, we can move ahead towards submission. The preparations are on track and are going full steam, but also if the FDA has further comments or requests, we will have a chance to address them ahead of the submission. So it's an important meeting to try and reduce the risk of delays or a possible rejection during the review process, which, of course, we want to avoid.

And looking at our U.S. endeavor overall, it's worth reminding ourselves that we have met the primary endpoints in both studies. There was no new safety signals. The secondary endpoint outcomes offer several results that we are hoping to convert into compelling label claims. FDA has given us Fast Track designation and have authorized an early access program, in which we are expecting the first patient to be treated this year. So it's, of course, always a bit advisable to be a bit humble in a process like this, especially when the FDA is involved, but the individual pieces are really coming together quite nicely.

So let's move on. Look at Page #4, please, which shows the longer-term sales development. You can see that we are now operating at sales levels that are higher than the COVID-19 years. And also this year, we are on track to set a new all-time high in sales. Even though Q3 was a bit soft in sales, it was still the best Q3 we've ever had, just like Q1 was the best Q1 and Q2 was the best Q2. Overall, in the first 9 months of 2025, we saw a sales growth of 18%, of which 12% came from the core business, and the remaining 6% were contributed by contract manufacturing revenue from Malaysia.

Again, the return to growth after the quite dramatic decline in 2022 following the COVID-19 period was a result of a quite decisive shift in how we use our resources away from noncustomer-facing functions into the front line. And just to illustrate, our headquarter team is now less than half the size compared to 2021. And instead, we have a much more forceful frontline team in our core markets.

On the next page, Page 5, you can see the effect on the bottom line. There is some cyclicality in our business with the winter quarters, Q1, Q4 being the strongest one sales-wise and the summer quarters showing lower sales and profitability. But you can see the clear trajectory of steadily improving EBITDA, both ex U.S. and on the company level. Again, we see a positive ex U.S. EBITDA year-to-date and also the group level EBITDA has improved quite well in the quarter, 8 percentage points, which actually would have been 11% without the exchange rate headwinds.

On Page 6. No change on how we see our addressable market. The market where we are active today represents a market potential of approximately SEK 3 billion to SEK 4 billion, and we see 3x the potential in the U.S. market, which we will talk about in just a minute. But it goes without saying that the U.S. could mean a step change for the company with a potential quadrupling of our addressable market once we have the approval.

And for the more short term, we have communicated a very simple financial target for the year, which is to deliver full year positive EBITDA ex U.S. in the low to mid-single-digit range. Year-to-date, we stand at 1% with the weaker quarters Q2 and Q3 behind us now, actually will have been 3% without the exchange rate, which gives me very good confidence that we will meet this target for the full year because, as usually, I would expect Q4 to be stronger than Q3.

If we then look at the performance by country, starting on Page 7 with Germany. Minus 9% in net sales is, of course, not what we want to see, especially not after our acceleration program has delivered good results in the first half of the year with 13% growth in the first half and even 19% growth in the second quarter. Year-to-date, we now stand at 6% higher sales than last year. So it deserves a closer look at what happened here.

So on Page 8, what we see here is data from the Robert Koch Institut. This is hospitalization rates for severe acute respiratory infections. This is not exactly our market, which is mechanically ventilated and sedated patients in intensive care, but it's a very relevant indicator, as a part of these patients will end up being relevant patients for us.

And what you see here is the comparison between 2024 and 2025. Both curves are higher in Q1 and lower in Q2 and Q3. And you don't have to be a visionary to predict that they will increase again in Q4. That is the normal seasonal pattern we see every year. But what's also quite evident here is that the yields are still quite different. So the flu season this year was more extensive and longer than last year, which has given us some good tailwinds in Q1 and Q2. But then the situation flipped and hospitalization rates have been significantly lower than last year since approximately May.

So if you look at Q3 in isolation, 34% less patients were admitted to German hospitals with severe acute respiratory infections. And Robert Koch Institut actually also publishes how many of these patients end up requiring intensive care. We don't have access to the raw data. So we can give slightly less accurate numbers, but also that group has decreased between 20% and 25% compared to last year.

We also collect our own data. So we're tracking a sample of hospitals, and that also shows that the ICU occupancy rate has decreased in Q3 compared to the previous quarter. The effect that this market development has on us after a quite strong beginning of the year is that less products have been used in intensive care during the end of Q2 and Q3, leading to later and then oftentimes also smaller reorders by many of our customers, which explains our sales decline.

The truth is we will have quarters like this every once in a while, because we cannot influence how the market develops. What's important from an execution perspective is that we stay focused on what we can control, and that is to maximize the time in the field, that is to focus on the right balance between new customers and increasing penetration in existing high potential accounts.

And these measures, by the way, are also exactly the measures that are going to be helpful in mitigating some of this volatility going forward. You will never be able to fully avoid it because respiratory patients are the majority of patients in the ICU, but expanding the use in more patient diagnosis, so we are less dependent on respiratory patients opening new accounts, so you're less dependent again and focusing on big university hospitals that are typically quite well occupied even when there's overall less patients.

In other direct markets, on the next page, we were up 22%, even though we saw some of the same market dynamics as in Germany, so less patients overall. The growth was once again led by our Spanish team, which has really shown fantastic growth over the last 2 years now. That was again the case in Q3 based on a good execution, but also based on a very, very strong network of believers and opinion leaders that the team has built on the customer side. And what's worked really well in Spain is that we do not just have the academic key opinion leaders who are oftentimes not treating so many patients anymore, but we have a lot of what we call bedside ambassadors, oftentimes younger doctors who treat a lot of patients, see the benefits of inhaled isoflurane sedation in real life every day and not just in studies, and who are at the same time very influential for their peers, so other doctors who seek advice on the best treatment options.

In the U.K., we were unfortunately hit by a temporary staff absence in the third quarter, which in a small team has a big impact because it leads to a quite significant reduction in field presence, so we could not deliver the growth that we were planning for. And when you have reduced resources, you often run into a typical problem that a lot of time is taken up by responding to the very good demand from potentially new customers, and you then have to neglect a little bit to maintain and drive the growth in your existing customers, and that is exactly what's happened in Q3 here. We have suffered from this phenomenon a little bit, but we'll soon have the team fully staffed again, and then also focus our energy on the right balance between new customers and existing customers.

What will also help a bit is that the MHRA has now also approved our pediatric indication in the U.K. as we now got some approval for the pediatric indication in all countries where we asked for it, which provides some upside as well. And in fact, we just went live in a new pediatric unit just this week.

In France, we continue to see a quite split performance with isoflurane customers performing very well, but in customers that are still using our devices with off-label sevoflurane, we continue to see sales decline following the SESAR study. Overall, this results in a rather flattish development, which is not good enough. So the plan for France is quite self-evident, focus on switching remaining sevoflurane users to isoflurane, and there we are really making good progress. If you look at the SESAR clinical trial sites, for example, which you would Imagine are the hardest nuts to crack given the seasonal results, 60% of those hospitals are today using isoflurane. So the conversion is progressing well.

Overall, I see our other direct markets or the direct markets outside Germany as a big success story. Of course, only a few years ago, Sedana was essentially Germany and not much else. Now we have built a business in these countries that represents more than 1/3 of our core business sales.

On the next page, on Page 9, we see our distributor business. This is the smallest part of our business, and you are right now used to seeing a bit of an up and down, because most distributor partners order less frequently and stocking effects tend to influence the order patterns more than in our direct markets. In Q1, if you remember, we had seen a decline in sales because we had a big order from South America falling into the comparative time frame. In Q2, then we were up 32%. And this time, we're relatively flat with a growth of 4%. And from an execution perspective, we are still pushing ahead with enhancing our focus and offer the best possible support to a few select key partners where we can jointly drive the most value.

Let's go to Page 11 and switch gears to the United States. Before I will ask Peter to take us through the details, let me briefly recap our strategic plan for the U.S. As you know, the U.S. is our largest growth opportunity. We have estimated the U.S. market potential for our products to roughly $1 billion, so SEK 10 billion to SEK 12 billion. So a market entry in the U.S. would instantly quadruple our addressable market. This is because of a high number of ventilator beds in the U.S., but also a medical practice that favors intubation and mechanical ventilation much more than in Europe, and also an overall quite attractive price level.

We do see a very good product market fit, for example, because of the proven opioid reduction that our therapy has been shown to provide, for example, because a reduction in the ICU length of stay is generally a very effective driver of the adoption in the U.S. more so than in Europe. And also because the guiding thoughts behind existing treatment guidelines such as fast wake-up, early mobilization, early ICU discharge are quite in line with some of the benefits of inhaled sedation with isoflurane.

And on top of that, as we've discussed before, Peter and his team have done a really excellent job in building a network of key opinion leaders in our clinical trial sites that are very support of our therapy and already very active speaking about inhaled sedation at different global conferences.

So we have a high market potential, a good product market fit, a KOL network you got to get started, and also an early access program that will allow hospitals to get trained and started before the actual approval. Therefore, we continue to believe that we can create the most value if we launch ourselves in the U.S., capture more of the upside and generate proof that this therapy can be successful, while then over time keeping the option open to either scale up ourselves and take it all the way or at some point to complement our presence with a partnership if we deem that can create more value.

Now with this, let's move to the next slide, and I will hand over to Peter for our U.S. and medical update.

Thank you. Yes. So as Johannes mentioned, we have the clinical trial sites that were very active in the trial, 31 different hospitals across the U.S. that enrolled 555 patients over the course of 2 years, and they continue to be very excited and interested in inhaled sedation, which, of course, is nice to see.

We can move over there to the next slide, please. So as Johannes alluded to, we are sort of on a good track towards our NDA submission with the 2 Phase III trials that both showed noninferiority for the primary endpoint and opioid reduction and other benefits that we know of when it comes to inhaled sedation such as fast time to wake up and positive data when it comes to ICU stay and mortality. And these studies are being prepared now together with the pooling analysis and it will be submitted early next year. And in parallel with that, we have the early access program that is being initiated, and we're looking forward to the pre-NDA meeting later this year, and we'll get guidance for the FDA on how they want to see the submission.

And if we move to the next slide. So the early access program, for those who haven't heard of it before, it's something that you get for patients that have a life-threatening condition and where the current therapies are not successful enough. And we have applied for this with the FDA and got a green light for providing a therapy free of charge to hospitals who request it. And the patient category is the difficult-to-sedate patient group, which is a patient group that occurs -- you see these patients with different kinds of conditions that are typically mechanically ventilated and with different background diagnoses, but do require high doses and different combinations of IV drugs. And in this scenario, inhaled isoflurane sedation has been shown to work clinically the most popular indication across all ICUs that use our therapy.

And this is something that we can do until we get a marketing approval, and it's open to all interested hospitals, expanded access program. And this, besides being something that's helpful for patients that are struggling to be comfortable and safe in the ICU, it also offers an opportunity for us to continue training physicians and ICUs when it comes to inhaled sedation. And that, of course, gives us a very good start at the launch, because these hospitals will be proficient and there will be experts in inhalation. And also, it's an opportunity for us to refine our training and the whole supply chain, et cetera ahead of launch.

And currently, we have 11 hospitals that have expressed interest, and we're taking them one by one. So we're working with the finalization of the contracts for the first hospitals and also have set up a supply chain for all our products, and we expect to see the first patients treated within the EAP before the end of this year.

We can go to the next slide, please. And so in par with this, we are driving a lot of medical activities around the globe, mostly focusing on Europe, of course. So a lot of different activities ongoing in its workshops, round tables, symposia and webinars that we've been running. And they've been one of the activities, of course, after the SESAR study in the spring was to educate people on the differences between off-label sevoflurane and on-label Sedaconda (isoflurane). And it's also been about diversifying from patient groups such as a difficult-to-sedate patient or respiratory patients to other patient categories that are intubated and require sedation.

And most recently, this week, we did a round tour in the U.K. where we met clinicians together with one of the authors actually of the SESAR study, who was also helping describe the difference between sevoflurane and Sedaconda (isoflurane) and also local ambassadors. So we met representatives from 10 different hospitals in London, Liverpool and Bristol.

And with that, I'd like to move over to Slide 16, which is you, Johan. Please.

Thank you, Peter. Yes. So on the next slide here, we present our financial results for the quarter in some more detail. So we report net sales for the quarter of SEK 41 million, which is up 4% in reported currency or 7%, excluding exchange rate effects. And if we were to exclude our contract manufacturing business in Malaysia that we acquired last year, sales would have been SEK 39 million, so down 2% in reported currency and only slightly up excluding exchange rates.

So as Johannes has described, we have seen low ICU occupancy during the summer months and through Q3, in particular, across our main markets. In particular, this was the case in Germany, as you have seen, where we saw sales decreasing 12% in the quarter compared to the same period last year. And excluding currency effects, sales were down 9%.

Our other direct markets performed better despite some of the same market headwinds. So overall, our other direct markets report growth of 18% in reported currency or 22% excluding FX. And as has been the case for some quarters now, the main growth engine in this group of countries is Spain. Our distributor markets showed essentially flat growth in the quarter compared to last year in reported currency, 4% growth if we exclude exchange rates.

On the gross profit side, we report close to SEK 30 million gross profit for the quarter, which is up slightly compared to a year ago. And if we look at the gross margin, we report 71.6% gross margin in Q3 this year. That's up from 71.2% in the same quarter last year. So what we're seeing with regards to the gross margin is that we are now experiencing the positive effect from reduced cost of goods for our main product, the Sedaconda ACD, following the acquisition of our main supplier in Malaysia, Innovatif Cekal, last year.

But important to note that at the same time, we have, of course, added contract manufacturing to our overall business, which introduces a slight headwind because, of course, the contract manufacturing business has a lower gross margin than our core business. So important to be aware of that. But of course, over time, as we've discussed previously, we expect the positive effect on the gross margin to dominate, and we're well on track on realizing that.

If we look at EBITDA in Q3, we report for the group minus SEK 5.6 million EBITDA. That's an improvement by SEK 3 million compared to a year ago. And if we look at EBITDA ex U.S., which is what we base our full year financial target on, we report a negative SEK 1.7 million for the quarter despite the market headwinds that we are experiencing. So a clear improvement also there by slightly more than SEK 3 million compared to a year ago. So we are seeing a good reduction in operating costs in this quarter compared to a year ago. And we continue, of course, to look for cost savings and find efficiencies where we can find them, especially in our headquarter functions to be able to continue to reallocate resources as much as possible to the front line.

And if we look at the size of the staff, that has increased. So a bit counterintuitive to show these kind of cost reductions at the same time that we increased the staff quite a bit, but that's a function, of course, of the acquisition of our new manufacturing facility in Malaysia, which is behind the increase in staff.

And then on the next slide, we can look more closely on our cash flow and cash situation. So cash at the end of the quarter stood at SEK 112 million compared to SEK 131 million at the end of Q2. So the change in cash position is negative SEK 19 million for the quarter, and that's driven very much by our U.S. CapEx. So as you know, we are still spending money in the U.S. in preparation of our NDA submission. If we look at the cash flow from operations for the quarter, negative SEK 1.1 million. That's a pretty significant change relative to a year ago when it was negative SEK 29.3 million.

So if we break that down, we have cash flow from operations before changes in working capital, which has improved to now being negative SEK 4.7 million for Q3 this year compared to negative SEK 9 million last year. And then in addition to that, of course, we have some cash flow resulting from changes in working capital. So that includes, as you know, changes in inventory, changes in short-term receivables and short-term liabilities, which then add up to the remaining delta there in the cash from operations this year relative to last. But clear improvement, which is important, of course, in the cash that we're generating from our operations in Europe.

Cash flow from investing activities for the quarter, negative SEK 15 million compared to negative SEK 37 million in the same period last year. So that change or the reduction in CapEx is very much a reflection of the fact that we're now spending significantly less in U.S. CapEx, but there is, of course, some U.S. CapEx remaining related to our NDA submission preparations, and we expect CapEx related to U.S. now to stabilize at this new and lower level over the coming several quarters going forward. So a clear difference, of course, to what you've seen in recent quarters and especially the recent few years when the U.S. clinical trials were up and running. So total cash flow for the third quarter of this year of negative SEK 17 million compared to negative SEK 67 million in the same quarter last year. And in terms of liquidity management, we still have over half of our remaining cash in U.S. dollars, and we continue to expect to be sufficiently financed to achieve U.S. approval.

And then on the next slide, we have our current shareholder list and, of course, continue to be thankful for the support and hope to continue to engage with all these partners going forward as well.

With that, I will hand the call back to Johannes.

Thanks, Peter and Johan. We've arrived at the last slide here. For me, I see 3 big reasons to believe in Sedana Medical success. Number one, and the foundation of it all is a therapy that makes a difference for critically ill patients every day. We help them wake up faster, we help them recover faster, communicate with their families earlier, and leave the intensive care unit earlier.

And with more than -- or actually several hundred thousand patients and more than 1,000 hospitals around the world treated and more than 1 million sedation days under our belt, we can say with some confidence that we are truly living up to our purpose, which is to improve life during and beyond sedation. Every single ICU patient has a life that is worth getting back to after ICU and no one should be in the ICU longer than necessary. So true patient benefits and cost savings for the hospital as well.

Number two, we have, as you've seen, a growing core business mostly in Europe. We've had all-time highs in quarterly sales now in 11 quarters in a row, and we are now at a point where this business is generating positive EBITDA, so provides proof of concept and also a stable platform for a future U.S. launch.

And number three, as we've discussed, as you have heard, we are getting closer and closer to the U.S., which one day should become our largest market as we would quadruple our addressable market upon U.S. approval. With 2 successful U.S. studies, FDA Fast Track designation and an early access program kicking off, there are a lot of positive indicators. So we are very confident that inhaled sedation with isoflurane will benefit also U.S. patients in the near future.

Thank you very much for listening, and we will now open it up for your questions.

[Operator Instructions] The first caller in, we have Filip from Pareto.

I've got a few questions here, but I'll take them one by one. So the first one is about Germany. So you had quite strong headwinds here from the market. But if we look beneath that, how has the underlying progress been? So I'm thinking more about increased penetration rates, et cetera.

Yes. So that's a very good question. And it's not always easy to differentiate between market circumstances and execution. So sometimes when you have market headwinds, it's a little too easy to blame everything on that and then you forget about the execution. So you know, of course, that after the last year, we have focused a lot on execution in Germany. We've put in place an acceleration program, which has shown good results in the first half. In the first half, we grew 13%. So these were things like making sure we spend as much time in the field as possible.

Let's make sure we spend the time with the right customers, so the ones that we can we can grow the most. Let's also make sure we have the right balance between opening new customers and increasing penetration. So all of these things have been going on since the beginning of the year, and we're seeing good progress with it. And of course, it's quite striking that the same team doing the same things has grown 19% in Q2, and then it has been shrinking 9% in Q3. So it's very obvious that the main contributor to this performance is -- or the difference in performance is the market. But of course, we need to be fully focused on execution as well. So overall, there's nothing to be concerned about on the execution side. We will carry on, but at the same time, not lose focus on the execution.

Yes. Okay. And then I also noticed, based on the data you showed on Slide 8, that last year, 2024, there had already been an uptick in the ICU patients, while it has remained flat this year. So is it possible to give any sort of indication around the start in Q4 if the headwinds have remained or have eased?

Yes. So if you were to -- so these data are publicly available, right? So you can basically update them every week. What we have seen in October is a bit of a continuation. So in 2024, you see that these respiratory infections, hospital admissions have started to increase. We are not fully seeing that to the same extent yet as we're still a little bit behind. But for what is worth my own sentiment from -- the ICUs seem to be filling up. So we see the normal seasonal increase, even though it's maybe a bit weaker than last year.

Okay. Good. Then a few questions around the pre-NDA meeting that you have upcoming. So firstly, do you have a specific date for it yet? Can you share whether it's early or late in the quarter?

Yes, it's relatively early in the quarter. So we will get updated on that reasonably soon.

Okay. And is it possible to also share a little bit more details around what you will be discussing. So I'm thinking mostly around like what sort of risk you see related to the topics that you're going to discuss, potential things that could come up that could have an impact on the submission time line.

Yes. So the very idea of a pre-NDA meeting or at least how we are using it is to reduce the risk, because the one thing that we want to avoid is we submit a file and then we get sent into an extra round, either causing delays or a complete response letter, as you've, of course, seen too many examples of, especially in Sweden lately. And that we want to avoid. So we have asked very concrete questions that is around the format, the contents, the presentation of the data and so forth in the file.

An example is the pooling analysis that the FDA has requested. So we are presenting what we've done in the feasibility studies, which of the endpoints we have pooled the results and so forth and trying to get confirmation that this meets the expectations. And the hope is that with positive responses on these questions, we have reduced the risk of the submission and can follow our time plan.

So things for the preparation are progressing according to plan. But even if you have a scenario where the FDA has more requests or they want things differently or they have maybe additional wishes that they didn't have before, then it's also much better to have a chance to address that before the submission, because then you will put in a better file and you avoid delays and additional costs further on. So you used that in your question yourself, it's a risk-reducing meeting.

Yes. All right. But you're also going to talk about potential Fast Track benefits, right? So I was just also curious around like what are the arguments for and against you receiving any sort of those benefits?

Yes. So the decision of -- so we have Fast Track designation from the FDA. What that means these days is mostly that we have a little bit easier access and it's easier for us to communicate with the FDA. And unlike maybe what you hear in other places, our experience is a very constructive and good dialogue. So that's the main benefit now. But when it comes to the review, we have the right to apply for priority review, which would reduce the review period from 10 months to 6 months, which is, of course, a big benefit. That is a decision that the FDA will take.

We will apply for this with the submission. So when the file goes in, you put your application. And then, as you probably know, the submission is followed by a 2-month validation period where the FDA is checking whether the file is complete, whether it makes sense for them to review and so forth. And as part of that validation period, they also take a decision on whether the priority review is granted yes or no. And if it is granted, then you get a PDUFA date in 6 months. And if it is not granted, then you follow the standard time line of 10 months. This is a decision that the FDA takes.

An argument for receiving it is that this is a therapy that at least we believe and, based on the Fast Track designation, also the FDA seems to believe that brings potential benefits to U.S. patients, and it's worth bringing this therapy to the market faster. Arguments against could be anything from capacity constraints to complexity of the file that needs more time. So this is really a decision that we cannot influence. But of course, we will try to put the best case forward.

Okay. Perhaps just a question around the pooling analysis, which is now completed, if I understand correctly. So my question is, have the results aligned with your expectations? Have there been any surprises, so to say, or...

Yes, I can answer that one. So no, I would say there haven't been any surprises. Just to mention, at the time when we were requested to consider pooling of our efficacy endpoints with the SED001 study, that was a positive surprise to us because we knew the results from SED001, which were in favor of isoflurane. We didn't know the results of the U.S. study. So you could say, it was a sort of insurance to be able to pool in those data in case any of the U.S. study didn't show a noninferiority or didn't show opioid reduction or there was something else that didn't turn out the way we had expected. And now they did. So in some sense, you could say that part of the sort of excitement about having getting to pool SED001 with the U.S. studies was sort of neutralized by good data from the U.S., but the other aspect is the possibility to get better power and more precision in the estimates and also to look at subgroups.

And where those analysis are just dropping in now as we speak. And to date, there have not been any unpleasant surprises. I think that the data show that our treatment does pretty much the same if you're in Europe or if you're in the U.S. And that, of course, is a very robust statement for us to make to the FDA.

Okay. Have there been any positive surprises or any of the endpoints that have tilted into significance?

No. No new -- sort of no bad nor good news. I'd say we have a stronger case now that we have pooled the data and can look into the subgroups. So I would say, for example, looking at subgroups, looking at opioid reduction, for example, when you look at the pooled data, you see that all subgroups have opioid reduction. And that, of course, is very valuable because it shows that it's not just one patient group, for example, surgical patients that benefit from having isoflurane. It's all kinds of patients, old and young and very sick and more healthy patients. So I would say, in some sense, I would say, it's reassuring, I would say. No big surprises in any direction, but reassuring the data when you look at the pooled estimates.

Okay. And we'll move on to Mattias from SEB.

I will stay with the previous question here for a bit and ask if you can share anything on mortality or ICU-free days or anything around the pooling analysis?

Yes, those are areas that will be quite useful. So I mean, the health economic endpoints such as ICU-free days, that will make for a very, very useful publication, right? Because we had very consistent results between the European study and the 2 U.S. studies. We saw less time in the ICU across the board, more ICU-free days. So if we have a publication based on -- here we pooled 3 randomized controlled trials in Europe and in the U.S. and you're saving -- or you have 1 more ICU-free days or 1 point, whatever it will be in the publication. And that translates into, depending on the situation, between $5,000 and $11,000. That is, of course, a very powerful tool that you can use with procurement departments in hospitals.

So that's an example where the pooled analysis will be translated into a very valuable publication besides the fact that, hopefully, it will also contribute to the FDA seeing this as a very robust data for approving the drug. And the same approach goes for mortality, of course, as well, if there's a way for us to build that into a publication, that can be very supportive for the launch.

So while you answered that you do not see any positive nor negative surprises, it is still possible that something could come out of this analysis that support those statements? Or how should I...

If you have a publication showing a day difference in the ICU length of stay, maybe that's not kind of a traditional FDA outcome that will make the difference between getting approval or not. But we all know that the approval and the clinical benefits alone is not what is going to drive the uptake, and people are going to look at the health economics in the U.S. much more. So maybe it is not surprising in that sense because we knew that our therapy will reduce the time that patients spend in the ICU, but that doesn't make the message less powerful. So that will be an important tool when we launch.

So I could just add to what I said, I maybe didn't spell it out enough when I responded, that there's nothing new. If you look at the results from Sedaconda study and you look at the individual U.S. studies, for example, you will find that ICU-free days are more for isoflurane, not statistically significant. And that means, obviously, that when you pool the 3 studies, you will find similar results. And that, of course, is also very reassuring. And as Johannes was alluding to, even without statistical significance, you can have something that's clinically significant or significant from a health economics perspective.

If we talk about mortality, for example, we had a 5% difference in mortality in one of the U.S. studies, 4.3% difference in the other study, which favor isoflurane. So overall, I mean, we are very happy with the results. Even though many of them maybe are not translatable into a label claim, they will be very useful when we launch from a medical affairs perspective and from a health economics perspective.

Okay. And just as a follow-up on the pooling analysis, when is it possible that we can see the results? Or how will this be presented?

The pooled results are not results that we normally post on sort of clinical trials or anything like that. But there is an intent to liaise with an academic center and make a publication out of the pooled results. So that will be peer-reviewed publication, which I think is the strongest way that we can present the data.

Perfect. And then if you look at the U.S. submission, it sounds like everything is intact. Could you maybe speak a little bit about the time after submission? You talked on previous questions quite in detail about this, but it sounds like maybe you can have the product launched towards the latter parts of 2026? Or is it rather 2027 that you see likely for the product to be launched in the event of an approval?

Yes. I mean, as we have discussed before, it's always -- if you are in an FDA process, it's always, to some extent, speculation to talk about approval times and launch time lines, right? What I can say is if everything goes optimally, so pre-NDA meeting goes perfect, we have alignment on everything, we file the submission as we have planned, and then get Fast Track or get Priority Review or a 6-month review time and that goes well, then there's a scenario where we would get approval towards the end of next year, which is very soon. It is, of course, a very nice scenario, but it's also part of the truth that we are fully in the FDA's hands. And unforeseen surprises can come up. We're trying to mitigate them as much as we can. Of course, as I've said, we're trying to derisk this as much as possible before submission. But it is possible, yes. The base case assumption is probably a launch in 2027.

Then I want to follow up a little bit on Germany, if that's okay. If it is clear to you that you are taking market share in Germany with growth of sort of 5% to 6% in local currencies, if you look on 2024 and this year, I'm also asking if you could talk about the scope to further increase the market shares in Germany in coming years? And what sort of brings you comfort that it is not sort of the market shares that we are looking at in Germany? I think that would be helpful to cover on this one.

Yes. So we communicated these penetration levels on a yearly basis. The reason for that is that there's no perfect data that gives us exactly the size of the market that we operate in. So you would need the number of patients in intensive care that are intubated and sedated. And you can get things like how many patients are in the ICU, but you don't know how many of those have a tube in their throat and how many are just not receiving ventilation or are receiving noninvasive ventilation. So there's no perfect data there. So if we were to communicate this on a quarterly basis, there's a bit of a risk of not being precise enough. So that's why we do this on a yearly basis. We are seeing progress. Last year, the penetration was 13%. What we mean by penetration is how many days of all the sedation days in Germany was our products used. That's around about 13% last year. We see an increase this year.

And to your question, how high can this go, or have we reached a ceiling? We do, also in Germany, even though it's maybe a bit more mature market than other markets, we do see quite substantial regional differences. And some regions are upwards of 20% penetration and even more and some are much lower than that. And then you see hospitals that have 50% penetration, some have 80% penetration. So there's no reason to believe that 13% should be the limit. So what I usually like as a proxy is if you can reach certain penetration levels in a region, so individual hospitals is something else because you will always have outliers, but if you can have penetration of whatever, 25% in an entire sales territory in Germany, which can easily be, I don't know, EUR 2 million sales or so, that gives you an idea of what should be achievable as a national average as well by transferring best practices and making sure we have the same good execution and continuity in the sales rep position. So 13% is definitely not the ceiling.

I think that's a good answer. And then lastly, sorry for having a lot of questions, around the lower costs in the quarter, if those can be extrapolated. I know you have seasonally higher costs in Q4 typically. But in general, sort of should we expect cost to be sort of stable or slightly down, excluding the U.S. OpEx, of course? Or how do you see it?

Yes. No, that's fair. The one thing to think of -- so we have worked or continue to work on our cost structure in the first half of the year, and we see some of these efficiencies come through in Q3. What you have in Q3 is a vacation period, so then the activity level is typically a bit lower. So there's less conferences, less travel. So that shows a little bit. So sometimes you have -- if you look at historical years, you will see that the cost level in Q3 is often a bit lower, but it is also a function of us having continued to work on the cost structure.

Okay. And that concludes the Q&A. Thank you very much, Johannes, Johan and Peter for your presentation and answers. And thanks to everyone for joining this Finwire presentation with Sedana Medical. And I wish you all a great rest of the day. Thank you.

Thanks a lot. Have a good weekend when it comes.

Hello, everyone, and welcome to today's presentation with Sedana Medical. With us presenting today, we have the CEO, Johannes Doll; CFO, Johan Spetz; and CMO, Peter Sackey. [Operator Instructions] And with that said, please go ahead with your presentation.

Thank you for the introduction, and welcome to our Q2 report presentation. I know that some of you are taking a break from your summer break to be with us, which we appreciate a lot. So thanks a lot for taking the time with us today.

Let's start on Page 3, please. The first half of 2025 is over, and it was a very successful period for Sedana Medical. We have had new all-time highs in sales. Q1 was the best, Q1 we've ever had and Q2 was the best, Q2 we've ever had. We're looking at a positive year-to-date EBITDA in our ex-U.S. business and are on track to achieve our financial target. And in the U.S., we've received positive clinical trial results. We got an Early Access Program approved and have FDA Fast Track Designation. So overall, many reasons to be proud of the progress we have made during these 2 quarters.

Let's dive into it. Q2 sales landed just under SEK 50 million, a year-over-year growth of 27%, of which 21% were organic growth and 6% came from contract manufacturing revenue stemming from our newly acquired manufacturing plant in Malaysia. And what really stands out this quarter is that we had excellent performance in our main market, Germany, with 19% growth, which I'm very happy about because, as you know, we've been working hard to reignite growth after having a slightly lower growth year in 2024 with only 5% growth. We saw slightly lower growth in our other direct markets this time, but still 22% up and 32% growth in our smallest part of the business, the distributor markets.

Another highlight we've just communicated is that the results of our paediatric study was published in the Lancet. The paediatric study overall is a real success story, in my opinion, after we initially got quite negative reaction on the stock market when the data were published. But since then, we've received approval for kids in 13 countries. We have received a total of 3 extra years in data exclusivity and market protection and now this publication in one of the most prestigious journals.

The good sales performance translates into further improvement of the bottom line, where we have seen a steady improvement all the way since 2022 through a lot of focus on commercial execution and at the same time, streamlining our cost base and noncustomer-facing functions. In Q2, the ex-U.S. EBITDA was in balance around the 0 point, and year-to-date, we're looking at 4% positive EBITDA, excluding exchange rate effects, which is fully in line with also our financial target for the year, which is to achieve positive ex-U.S. EBITDA in the low- to mid-single-digit range.

I'm really looking forward to also the second half of the year because we will see the full effect of our newly acquired manufacturing plant on the gross margins, which we have started to partly see now already in Q2.

On the U.S. side, we had several very good news as well. Early in the year, we had communicated that we've met the primary endpoint in both our pivotal trials and that the safety looked good also. And now we also know that the secondary endpoints have turned out positive with, for example, a greater reduction in opioid dosing than propofol, fast wake-up times with more than 75% of patients being awake within 60 minutes after treatment and also trends towards better mortality versus propofol and, for example, more ICU-free days in both trials.

Apart from that, we are following our plan and still expect FDA filing in the first quarter of next year. And even before that, in the fall, we expect the first patient to be treated under our Early Access Program.

Let's move to Page 4, please. Looking at the longer-term sales development, you can see that we are now operating at levels that are higher than the extraordinary COVID-19 years. And also this year, we are on track to set a new all-time high in sales. In the first half, we saw a sales growth of 22%, of which 17% came from the core business and the remaining 5% are contract manufacturing revenue from Malaysia.

Again, this is a result of a quite dramatic shift in how we use our resources away from noncustomer-facing functions into the front line, just to illustrate that our headquarter team is now approximately half the size compared to when I started in 2021. And instead, we have a much more forceful frontline team in our core markets.

On Page 5, you can see the effect on the bottom line. There's some cyclicality in our business with the winter quarters, so Q1 and Q4 being the strongest ones sales-wise and the summer quarters showing lower sales and profitability, but you can see a clear trajectory of steadily improving our EBITDA, both ex-U.S. and on the company level. With ex-U.S. EBITDA around 0% in Q2, we see a SEK 4 million positive ex-U.S. EBITDA since the beginning of the year, which excluding currency effects is 4%. And also on the group level, we see a SEK 12 million improvement compared to last year.

On the next page, Page 6, no change on how we see our addressable market. The markets where we are active today represent a market potential of approximately SEK 3 billion to SEK 4 billion, and we see 3x that potential in the U.S. market, which we will talk about in just some minutes. For the more short term, we have communicated a very simple financial target for the year, which is to deliver full year positive EBITDA ex-U.S. in the low- to mid-single-digit range, positive, of course. Year-to-date, we stand at 4%, which gives me good confidence that we will meet this target for the full year.

As usually, I would expect Q3 to be a little lower sales-wise, just from a seasonality perspective, and then we'll hopefully have a stronger Q4. And again, for the full year, we should meet our target.

If we then look at the performance by country, starting on Page 7 with Germany, you know that we had a little bit of a mixed year last year with a very strong Q1, a very weak Q2, then a solid Q3 and a flat Q4. And overall, all of that led to a full year growth of 5%. We had an explanation for that as we did not have a stable team, especially in the second half of the year with some turnover in the field force. But of course, we were not satisfied with this level of growth in our main markets, and we launched a sales acceleration plan in response.

And now we are 6 months later and can see 19% growth in Q2, admittedly compared to a slightly weaker comparator quarter last year, and also 13% growth year-to-date. And I'm very, very happy with the progress we've made. The team is fully staffed again. The new colleagues have been onboarded successfully. And in general, we have improved our focus on high potential accounts. We have improved our commercial effectiveness, and it's great to see the passion and motivation that we have in the team.

We will likely not see 19% growth in every quarter from now on. Again, Q2 last year was a bit weak, but we are definitely on the right track and 13% penetration of the market potential that we saw during last year is definitely not the ceiling. On the contrary, I think we still have some very good growth potential in Germany.

On the next page, and our other direct markets, a lot of the positive things I have said about Germany are also true for our Spanish team, which has really shown fantastic growth for several years now. That was again the case in Q2 based on a good execution on the ground, but also a very strong network of believers and opinion leaders on the customer side. And what has worked really well in Spain is that we do not just have the, let's say, academic key opinion leaders who are oftentimes not treating as many patients anymore, but we have a lot of what we call bedside ambassadors. So oftentimes younger doctors who really treat a lot of patients, see the benefits of inhaled isoflurane sedation in real life and not just in studies and who are, at the same time, very influential for their peers, so other doctors who seek advice on the best treatment options.

The reason that the overall growth rate in our other direct markets is this time a little bit lower compared to what we've been used to in the last quarters is a less good performance in France and U.K. this quarter.

In France, we have some execution issues that we need to address where we have not managed to spend as much time with growth customers as we had planned to, but we also see some effect of the SESAR trial, which is different from all other countries. It's not an effect across the board, but actually, we see a very differentiated picture where our customers who use our Sedaconda isoflurane have grown quite well, but customers that still use off-label sevoflurane with our devices have dropped in sales. And overall, for the first half, we are only slightly above last year's level. So we're still growing, but very little, which is not good enough. So the plan for France is quite self-evident. We need to fix the execution issues and at the same time, really double down on switching remaining sevoflurane users to isoflurane because it's the better treatment for patients, but also better for the sales.

In the U.K., we've seen a temporary sales decline in the second quarter, which, of course, we don't want to see either. Here, the reasons lie in specific circumstances in a few specific customers. For example, we had to temporarily halt delivery in an account that didn't pay the invoices or we're dealing with personnel changes on the customer side that have affected the use of our therapy. But the good news here is that we have several important new accounts lined up for go-live in the second half. So I'm expecting a return to growth quite soon. And hopefully, this will turn out to be only a small bump in otherwise a steep road ahead.

Overall, for the other direct markets, we still had 22% growth in the quarter and 37% in the first half. So clearly, still the fastest-growing part of our business.

On Page 9, we see our distributor business. This is the smallest part of our markets in the first half, approximately 7% of our core business sales and you're by now used to seeing a bit more of an up and down because most distributor partners order less frequently and stocking effects tend to influence the order pattern a bit more than in other direct -- in our direct markets.

But last quarter, we had seen a decline in sales because we had a big order from South America falling into the comparator time frame. This time, we are up 32%. And from a strategic perspective, we're still pushing ahead with enhancing our focus and offer the best possible support to a few select key partners and have a more light touch support model for others.

With this, let's go to Page 10, and let me hand over to Peter to talk about our paediatric publication and then, of course, the U.S.

Thank you, Johannes. So earlier this week, the paediatric IsoCOMFORT study was published in the Lancet Respiratory Medicine which we're very pleased about. The results of this paediatric study are as earlier communicated that isoflurane was non-inferior to intravenous midazolam, the only approved IV sedative for paediatric action in the time to extubation and more predictable extubation and also reduced opioid consumption compared to midazolam.

And the conclusion in the study, which is our conclusion also is that this supports the use of isoflurane-based inhaled sedation as an alternative to intravenous midazolam. And that was also the conclusion that was made by the competent authorities in Europe that approved the new paediatric indication for children between the age of 3 and 17, which is what we studied. So isoflurane is now approved. Sedaconda is now approved in 13 European countries.

And besides approving the therapy for children, we were also granted 1 extra year besides the 2 years that are normally given when the paediatric investigational plan has been executed is that we got an additional year because this was considered to be a superior therapy versus available therapies. So that was also very gratifying.

And the fact that this paper was published in the Lancet Respiratory Medicine is a quality stamp, I would say, on our study and on the results and will be helpful in the dissemination of our main clinical benefits of isoflurane and [indiscernible], both in the paediatric ICU world and in adult ICU world.

So the main -- the 3 main sort of differentiating factors when using an inhaled isoflurane is that it's always effective as a sole sedative, it's opioid-sparing and it's associated with rapid and predictable wake-up.

So with that said, we'll move over to Slide 11, which is the U.S. trial. As you know, this was a trial that we completed last year, and we read out the results this year and posted them on clinicaltrials.gov. The 2 studies were identical studies, INSPiRE-ICU 1 and 2 that we ran together with clinical investigators in 31 clinical trial sites across the U.S.

Let's move to the next slide. So there was a lot of enthusiasm during the trial -- during the trials, I should say. As I mentioned, the 2 identical trials evaluating the efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD, comparing that with standard care propofol. So 235 patients were randomized in each study and the primary endpoint was the percentage of time at target sedation level, assessed with the Richmond Agitation Sedation Scale.

And the key secondary endpoints were opioids, time to wake-up after sedation, cognitive recovery after sedation and the proportion of time with spontaneous breathing. And what we found was that isoflurane was non-inferior to propofol with regards to the primary endpoint. And we also have looked at the safety results, and they indicate tolerability and no new safety signals compared to what is known for isoflurane for anesthesia and for ICU sedation from our European trial.

Let's move over to Slide 13. When it comes to the secondary endpoints, just a brief view of what we have seen so far. These are data that have not been peer-reviewed, not published anywhere else in clinicaltrials.gov. But what the data tell us is that with isoflurane in the U.S. setting, opioids could be reduced compared to baseline more with isoflurane than with propofol with a reduction of approximately between 30% and 40% in the 2 studies. And why is this important?

Opioids have many dose-related direct side effects that are well recognized in the ICU, and they include constipation, respiratory depression, withdrawal, delirium. But there's also an association between the dose of opioids given during mechanical ventilation and the risk for persistent opioid use in the year after ICU discharge. So an opioid-sparing sedative may bring other benefits than what is seen in the ICU.

When it comes to the fast return to wakefulness, there was not a statistically significant difference between isoflurane and propofol in the 2 studies. But as Johannes mentioned earlier on, in both trials, it was clear that isoflurane was associated with the wake-up of approximately 3/4 of the patients within the first hour, and that is similar to what we found in the Sedaconda study and what we also have in our European label about wake-up. And this is clinically a very valuable feature.

Short and predictable wake-up implies that neurological assessments can be done with greater certainty than when there's risk for accumulation of drug. It means that patients may need to go for CT scans less frequently if you can feel confident that the drug is out of the system very quickly and also potentially can impact mechanical ventilation duration, ICU length of stay in a favorable manner.

And we know that with prolonged intravenous sedation, wake-up times can be very long and unpredictable, especially in patients with multiple organ failure, and these patients are very common in the ICU. We did find a trend towards lower mortality with isoflurane with a 5-percentage-point difference in both studies. And this is something that, of course, is a very good safety evaluation in parallel with the adverse event reporting that would indicate the safety of this therapy. And that's something that's important both for -- of course, for patients, for health care providers, but also for various committees and organizations that evaluate a new therapy.

We also noted, if you look at the 3 studies that we performed in adults that in average, there's 1 ICU-free day more in isoflurane patients than those receiving propofol for up to 54 hours. And this, of course, is something that is a valuable aspect when it comes to looking at the cost versus survival. And that may be a beneficial sort of aspect when we will be looking for access in U.S. ICUs.

And then finally, the general feature of isoflurane is well known and is in line with the clinical results, namely that metabolism isoflurane is minimal and is not required for elimination of the drug. And this means that in patients with renal dysfunction, hepatic dysfunction, this drug will not accumulate despite impaired such functions.

And I'd like just to move over to next slide, to Slide 14. Now we are in the waiting -- working hard with our submission for the NDA and the FDA review. In waiting for this, isoflurane can be used in the U.S., thanks to the Early Access Program that the FDA have approved.

And the Early Access Program is for difficult to sedate patients when intravenous sedatives cannot help the patients be at the targeted sedation level despite maximum doses -- maximum tolerated doses. This EAP is open to any hospital that's interested. They will be receiving our products free of charge. The benefits of the EAP are, of course, that patients that are difficult sedate can receive an efficacious therapy in waiting for approval.

Besides that, from our side, it's beneficial because it allows clinicians to use isoflurane in some patient populations that were not part of the clinical trials, for example, patients on ECMO or neurocritical care patients. It means that there will be continued use of inhaled sedation, isoflurane sedation during the review process. And that also means that hospitals and physicians will gain expertise and proficiency that we can leverage at the time of our launch.

And it also is an opportunity for us to develop all the different tools and have optimized the supply chain, et cetera, at the time of launch. And we currently have 10 ICUs that have expressed interest in the EAP. So we're working on contracting and supply chain in order to facilitate start of the EAP in the fourth quarter of this year.

And then we go to Slide 15. And I believe that's your slide. Back to you, Johannes.

Yes. Thank you, Peter. Just to reiterate, the U.S. is clearly our largest growth opportunity. We have estimated the U.S. market potential for our products to be somewhere in the area of $1 billion, SEK 10 billion to SEK 12 billion, which is 3x as much as in our current direct markets combined. And this is because of a high number of ventilator beds, but also a medical practice that favors intubation and mechanical ventilation more than in Europe and also an overall higher price level that you see, even though that is not built into that number yet.

We see a very good product market fit, for example, because of the proven opioid reduction Peter just talked about, for example, because a reduction in the ICU length of stay is generally an effective driver of adoption. And for example, because the guiding thoughts behind existing treatment guidelines, so fast wake-up, early mobilization, early ICU discharge are quite in line with some of the benefits of inhaled sedation with isoflurane.

On top of that, Peter and his team have done an excellent job in building a network of key opinion leaders already in our clinical trial sites who, as you have seen, have some of the premier names in the U.S. hospital landscape that are very, very supportive in giving advice, but also supportive of our therapy and already very active beating the drums for inhaled isoflurane sedation in different global conferences.

So if you put these pieces together, a high market potential, a good product market fit, a KOL network that is eager to get started and positive results from the trial, then it's quite clear that we continue to believe that we can create the most value if we launch ourselves in the U.S., capture more of the upside and generate proof of concept that this therapy can be successful in the U.S. ourselves, while then over time, keeping the option open to complement our presence with a partnership if we come to the conclusion that, that would create even more value over time.

Now let's hand over to Johan for some more details on the financials before I will close it off, and then we can open it up for your questions.

Thank you, Johannes. So if we turn to our financial results for the quarter on Slide 16, starting with the sales. So to reiterate some of the points made earlier by Johannes, we report net sales in the quarter of SEK 50 million, which is 21% above last year or 27% above last year if we exclude currency effects. And also, if we exclude the recently acquired contract manufacturing, our revenue would have been SEK 47 million, which means 21% growth organically if we exclude both M&A and FX, so 21% growth if we look at that. And it's driven by, in the quarter, very much a good performance in Germany, 19% growth in local currency as our acceleration plan is showing clear effects.

Other direct markets report continued good growth, albeit a bit slower than in recent quarters, 22% in local currency in Q2. And as Johannes pointed out, mainly driven by Spain. And we have our distributor markets where sales increased 32% in local currency. And then as you know now, we also report contract manufacturing revenue, and that was SEK 2.7 million in Q2 2025.

Gross profit for the quarter, we reported SEK 35 million, which corresponds to a gross margin of 70.2% which can be compared to 70.5% in the same quarter of last year. So steady gross margin at slightly above 70% continues to be the case for us. We are experiencing cost increases for materials and other key components. But as we have communicated previously, we continue to expect to see a positive gross margin effect from the integration of the acquisition of our supplier Innovatif Cekal in Malaysia during the second half of this year. So we still expect that to come through more clearly in our gross margin as we move forward from here.

Looking at EBITDA, we report EBITDA in the quarter of negative SEK 4 million, which is almost SEK 10 million better than the same period of last year. And also, if we look at EBITDA ex-U.S., we report a similar year-over-year improvement in the quarter so that we're now very close to breakeven also for Q2. And as Johannes pointed out, Q2 and Q3 are seasonally our weaker quarters. So good to see that we're close to breakeven also in Q2 ex-U.S. So again, compared to negative SEK 10 million in Q2 last year for EBITDA, excluding U.S.

So what you can see in our numbers is that we have been able to combine the sales growth that we are reporting with actually reducing overall OpEx slightly in Q2 this year compared to last year. So this year, we're at SEK 45 million compared to SEK 46 million last year. And of course, that translates into the EBITDA improvement, which we expect will continue going forward as we continue to grow, of course, and remain very disciplined on the cost side going forward.

The group has grown in terms of staff on the back of the acquisition of our Malaysian supplier in late 2024, and we are now 131 colleagues in Sedana Medical, including consultants, and that can be compared to 89 a year ago.

Then if we move to the next slide to take a look at our cash flow and cash position. We can start with the cash position. At the end of Q2, we had SEK 131 million in the bank, which is SEK 34 million lower than at the beginning of the quarter. And the 2 main drivers of the change in the cash position is mainly CapEx and U.S. CapEx related to our preparations ahead of the submission in the U.S. And we also have an effect of negative -- a negative effect from changes in working capital of minus SEK 10 million in the quarter.

But if we look at them in a bit more detail, so starting with the cash flow from operations in Q2 2025 was negative SEK 12 million. And again, a big driver of the negative number here is changes in working capital. So the cash flow from operations outside of U.S. has improved in line with the EBITDA development, but total cash flow from operating activities has been negatively affected by changes in short-term liabilities, negative SEK 6 million and also changes in short-term receivables, which had a negative effect of SEK 3 million in the quarter.

And I can add there with regards to the short-term liabilities that those SEK 6 million include an adjustment payment related to the sellers of our Malaysian supplier Innovatif Cekal during the quarter of SEK 3 million. So half of that change is related to that acquisition, which was as per the purchase agreement with the sellers.

So looking next at cash flow from investments in intangible assets in the quarter was negative SEK 17 million. And again, that's driven by U.S. CapEx related to the NDA submission and other operations. This is significantly lower than the same quarter last year when we had SEK 56 million of CapEx. And we expect this new lower CapEx level to remain sort of the level going forward here in 2025, so significantly lower than in 2024.

As you know, our clinical trials were completed in 2024, and that results in a significant reduction in U.S. CapEx this year compared to last.

So adding this all up, we have total cash flow in the quarter of negative SEK 31 million. And then there is a bit of currency effect as well to get to the full change in the cash position. But again, of that reduction in cash, SEK 10 million is due to changes in net working capital.

In terms of liquidity management, we continue to have a large part of our available funds in U.S. dollars. So still above 60% of our cash is in U.S. dollars, reflecting the fact that that's where the most of the cash outflow will continue to be going forward with, of course, leading up to the submission and thereafter as well.

We continue to have no external long-term debt in the company, and we expect to be fully financed to execute on our strategic plan.

Next slide, we have our updated shareholder list, and thank you for your continued support, as always.

And with that, I will hand back to Johannes.

Yes. Let's have a look at our last page. Let me wrap it up and recap the Investment case for Sedana Medical. As you know, our business model has the advantage of having a good chance for attractive profitability over time because we continue to see good gross margins of 70% and up with some upside now from the Innovatif Cekal acquisition.

So by definition, we can become quite profitable as a business when we reach scale. And at the same time, our customer base are intensive care units, so a relatively small concentrated target group that can be covered with reasonably low operating expense levels locally. And we already have proof of concept that, that model works in our main market, Germany, where the majority of ICUs are already our customers. The team is generating very attractive EBITDA margins on a local level already, and we see very good growth momentum also outside Germany. And while we're not at the same scale yet, almost all of our countries contribute positively with good local profitability by now.

So now it's all about reaching more scale, convincing enough hospitals to use inhaled sedation with isoflurane more broadly and achieve profitable growth that way. And for this task, we have convincing clinical and health economic data on our side, showing that patients really benefit from inhaled isoflurane sedation and that hospitals can save money versus the previous standard of care. And we have still lots of places to grow in Europe, as we have discussed and hopefully also soon in the U.S. where we have Fast Track Designation, the positive clinical trial outcomes and also the FDA authorization of our Early Access Program.

So all very positive signs towards a future U.S. business and still a balance sheet that allows us to execute our plan with no debt and SEK 131 million in cash and of course, a commitment to keep doing what we have done quite successfully for some time now to grow sales while being very disciplined on the cost side.

So that concludes our presentation. Thank you again for listening, and we will be very happy to take your questions.

[Operator Instructions] And we have Filip from Pareto.

Hi, can you hear me well?

Yes, perfect. Hi, Filip.

I've got a few questions here, but I'll take them one by one. So first off, just nice to see Germany performing well, but it seems like other direct markets lost some momentum. It's been a real growth driver now. So looking back, I think, for the past 9 months, the growth has been in the range of 40% to 60%. So now 12% for '22, excluding FX. So is it only these 2 countries, the U.K. and France that led to this effect? Or was there some kind of effect from Spain or some other markets as well?

Yes. So a clear answer to that. So our core markets within other direct markets is Spain, U.K. and France. There's a little bit of Benelux in there as well and some small Swedish sales, but the effect that you see this quarter is driven by U.K. and France as described. So no other effect.

Okay. And around France then, can you share anything more about what they are saying? So is it only the sevo users that have become more cautious in the user? Have you also had any changes in the sentiment to inhaled sedation as a class?

No, it's a quite clear-cut picture. So you can almost divide France into 2 halves. It's not exactly 50-50, but the customers that have either always used isoflurane or have now switched to isoflurane following the SESAR results are growing quite nicely. So we've seen good results.

The best performing accounts, by the way, in France are the ones that were SESAR sites, so participating in the clinical trial. So remember, it was a French trial that have after the trial switched from sevoflurane to isoflurane. So those are the ones where we see the best growth in France. But then reversely, we also see that accounts that have not yet switched to isoflurane, so that still use our devices with off-label sevoflurane. We've seen that customers are more cautious using inhaled sedation in that case, with sevoflurane in ARDS patients following the SESAR results. And that makes France quite unique.

So overall, you can tell from our numbers that SESAR has not had an effect on our growth. So our growth rate in Q2 was even higher than in Q1. So we've been able to manage that situation well and actually see the opportunities in it. So we didn't have a negative impact. So France is a bit -- stands out a bit from all the other markets in that sense because we still have a significant share of customers using sevoflurane because France has traditionally been a sevo country. So now the focus needs to be on switching that over to iso. And whenever we see that, we also see usually an increase in sales.

Okay. Okay. Perhaps switching focus a bit. So distributor markets picked up in the quarter now, and I know it's quite irregular the order pattern. So is it fair to assume that this quarter was unusually strong? Or what are your expectations moving forward now?

No. Well, it was not unusually strong because Q1 was quite weak, right? So year-to-date, we're still roughly in line with last year, so not a lot of growth. So from that perspective, we did expect a little bit of a catch-up effect in Q2 now. Overall, what's important from a strategic perspective is we still have quite a high number of distributors. So as a small company, we really have to focus. So we can't spend a lot of resources on supporting partners even if you would maybe like to do that, that generate very little sales. So we have to be really, really focused and offer the best possible support to, let's say, the handful of key partners that have the best growth potential and where we have the biggest business.

And with that strategy, I'm assuming that over time, we will see growth. But as you rightly say, there's a little -- there's going to be a little bit of up and down between the quarters. So it's not unusual to see a 30% swing in either direction. So from that perspective, you'll always have to look at a slightly longer-term trajectory in the distributor markets.

Okay. Moving over now also quite interested around the feedback you have received from the medical community now after the U.S. results. So it's been almost a month, I think, since you presented it. So what have you heard from the community in -- and I'm thinking both then in Europe and the U.S.?

Yes. So I can start and then, of course, Peter can probably give you even more insight. So one of the things we did relatively fast after the trial data were released, we brought the investigators from the U.S. trial together to discuss the results. And we had a lot of enthusiasm in that room. So in the sense of, wow, this is getting real. So these results look like we can really get the therapy approved in the U.S., and there was a lot of anticipation of having a treatment alternative.

And I think that the feedback has -- so the results have been appreciated. They've been considered very positively, especially when it comes to opioids, but also some of the trends we're seeing such as shorter or more ICU-free days or also the mortality difference that people are quite intrigued with.

So U.S., I would say, very positive reception. And of course, also in Europe, we are -- since the data have been made public, and we have a lot of doctors that are very curious what's going on outside Europe. We've received a lot of interest on the -- especially the mortality data because, of course, people have seen the SESAR trial. They've seen that apparently with sevoflurane, at least in ARDS patients, we saw a mortality disadvantage. And now seeing the opposite with isoflurane, I think, drives home that point that isoflurane and sevoflurane are indeed different drugs and people who have been seeing the benefits in their daily lives with inhaled isoflurane sedation feel very much confirmed in that approach.

Peter, what would you say?

I agree with everything you said, Johannes. I think one can add one aspect that when we had the investor call that we didn't discuss so much. But if going back to the anesthesia and volatile anesthetics, the history of these drugs is that there were 3 early drugs that were used a lot, halothane, enflurane, methoxyflurane considered very good, efficacious and so on. But over a few years after their introduction, they were found to have toxic effects and new drugs came, isoflurane, sevoflurane, desflurane. And today, no one considers methoxyflurane to be a volatile anesthetic that one would use except for immediate pain relief and this green whistle thing that you can use. But otherwise, it's not used for anesthesia.

And I think we're seeing the same development, same evolution in inhaled sedation that inhaled sedation for everyone 5 years ago was either iso or sevo. And I think we're learning more and more that sevoflurane is not the drug that one should use for prolonged sedation, whereas isoflurane appears very safe. So the reaction that we are getting is a lot sort of these are 2 different drugs. We realize now more today than we did before. And also many of the users are sort of reassured when they see the results from the U.S. study, as Johannes was alluding to, all outcomes were sort of either neutral or in favor of isoflurane compared to standard treatment in a completely inhaled sedation naive context, the U.S.

And if you look at the paediatric study, it's actually a similar kind of trend, small numbers, but there's no mortality in the first 30 days in the iso group. There's a 6% mortality in the midazolam group. So all looking at the big studies that have been performed with isoflurane, which are our studies, it's really clear that isoflurane brings benefits compared to propofol, whereas the large seizure study shows something else. So I think it's not difficult to explain with the help of the U.S. data.

All right. That's a good answer. I'm just thinking around the long-term follow-up that you had here also. So mortality at 6 months out from treatment also trended lower. How much weight has been given to that number, so to say?

So the mortality at 6 months is potentially there's a sort of possibility that -- I mean, the further you go from a short-term intervention, the less impact you'd expect to have from that intervention on mortality because there are many other reasons for dying. I mean we still see positive results in the 6-month mortality in both U.S. studies. I think there's no inhaled sedation study that has that long follow-up, but we included it because we were doing the cognitive outcomes analysis anyway.

So that also looks good. I think 30 days is the classical sort of mortality endpoint mark, if you like. But as I said, in the 6-month mortality assessment, we had something in the range of 10% almost difference in one of the studies and a few percent lower for the second study. So those data also look good.

Okay. And then just a final question, I think that's for to Johan. So it's around the cash flow and the U.S. regulators. So I think you mentioned now that maybe I just want to check so that I got this correct. So the investment in intangibles that you have now, is that the run rate going forward now for the rest of this year until you send in the -- until you submit to the FDA and then it will go down further? Or what are the expectations there?

Yes. I think that's a good starting point. I think it will gradually be coming lower during the second half of the year, but the big shift will then be once we actually submit in early next year. But of course, if you look at it, now we're at -- if you look at the first half of the year, we're at SEK 34 million CapEx. And really, it's -- almost all of it is U.S., and that's down from SEK 108 million last year, right? So that tells you sort of the shift. So hopefully, we'll continue on this or slightly lower level by quarter during the second half of the year.

Okay. And that concludes the Q&A session here. Thank you very much, Johannes, Johan and Peter for that presentation and answering all of our questions. And I wish you all a great rest of the summer. Thank you very much.

Thanks a lot. Enjoy the summer, everyone.

Hello, and welcome to today's webcast with Sedana Medical, where CEO, Johannes Doll; and CMO, Peter Sackey, will present the U.S. clinical trial secondary endpoint results. [Operator Instructions] And with that said, I hand over the word to you guys.

Thank you, and welcome to our call today. Let's jump right in on Page 3, please. I believe Sedana Medical is at one of the most exciting points in our history this year with 3 key assets or 3 key cornerstones that we see as the foundation for future success and value creation. At the heart of it all is, of course, our therapy, a therapy that truly makes a difference for intensive care patients.

One of the great privileges of my job is speaking with ICU doctors and nurses from around the world at a quite regular basis. And time and time again, they share stories of how inhaled sedation with isoflurane helps patients wake up fast, recover quickly, connect with their families sooner, and ultimately leave the ICU earlier. And we're not just talking about a handful of cases here. Several hundred thousands of patients have been treated using our therapy across well over 1,000 ICUs globally. And we are building on a strong base of clinical evidence that shows real patient benefits. And on top of that, also compelling health economic benefits. So hospitals can actually save money using our therapy.

And based on this, we have an existing business already in place, which is primarily focused in Europe today. Since the COVID-19 pandemic, we've delivered consistent growth. In 2024, we've hit a new all-time high in sales, and we didn't stop there. Q1 of this year was our best quarter so far, and we've also reached profitability in our ex-U.S. business, delivering an 8% positive EBITDA and generating positive operating cash flow as well. The third and biggest growth opportunity is the United States. We are now getting closer and closer to entering what could potentially be a step change in our growth trajectory.

Now the main results from our INSPiRE studies are public, and Peter will walk you through them in just a minute. With these results, combined with our Fast Track designation and an FDA-approved early access program and dossier preparations that remain fully on track, I feel we are well on track, and our goal is still to submit our application for marketing authorization in the early part of next year.

If we move to the next slide, there's no doubt the U.S. is our largest growth opportunity. More than 2 million mechanically ventilated patients are treated in U.S. adult ICUs every year. That translates into an addressable market for us of roughly SEK 10 billion to SEK 12 billion, so roughly $1 billion. That's about 3x larger than the combined opportunity in the countries where we are currently operating in, more ICU beds, more ventilated patients and also a medical practice that tends to intubate more often than in Europe. And importantly, that $1 billion estimate assumes no price premium in the U.S. That's a conservative view because, as you know, medical devices and sedatives typically carry a higher price in the U.S. than in Europe.

So how should we think about the value of this U.S. opportunity? It comes down to 3 things: the size of the addressable market, the likelihood of approval and our future market penetration. And first, the market, as I've already mentioned here, around $1 billion with upside potential from pricing, as I just said. Second, the likelihood of approval based on the data we've now received, we believe that probability has further increased. We met the primary endpoint. We saw no unexpected safety issues, and all other endpoints were either in our favor or showed no difference. And of course, there's never a guarantee. The decision rests entirely with the FDA. But on the clinical data side, we don't see any showstoppers.

And then the market penetration will depend on the label we receive and of course, on the strength of our commercial execution post launch. We believe our data supports a label that is similar to what we already have in Europe, which would give us some good differentiators such as, for example, a meaningful reduction in opioid use. And we are in a strong position to reinforce our case even more with pooled data from Europe coming in and planned further analysis.

With that said, I'll hand over to the main act today, and Peter will take you through the data in a bit more detail.

Thanks, Johannes. Move to the next slide, please. So as you may know, we've conducted 2 INSPiRE-ICU trials across 30 ICUs in the U.S., enrolling 555 patients, of which 470 were randomized. The rest were run-in patients. .

Next slide, please. And we completed enrollment last May, so a little bit more than a year ago. And the primary endpoint in these both identical design trials was the proportion of sensitive time at target sedation level assessed with the Richmond Agitation-Sedation Scale.

The key secondary endpoints were opioid redosing during sedation, which was the most important and most likely we believe. Second was time to wake up after sedation, time to reach RAS 0, meaning awake and alert or higher, cognitive recovery after sedation, looking at the CAM-ICU-7 60 minutes after end of treatment. And finally, the proportion of time which pertains to breathing.

These endpoints were designed with so-called sequential testing, meaning that if you meet the first endpoint statistically, then you can move on and analyze the second one and consider it to be something you could make a claim of, and the third and the fourth and so on. Should you fail to show that the first key segment point was statistically significant, the difference in favor of isoflurane, you could not go further. So we chose the order of these tests of these different variables based on the likelihood and the importance of the endpoint.

We can move over to the next slide, please. We presented the results at a meeting recently here in Stockholm, where we gathered the most important contributors from the U.S., the principal investigators from the study sites, and we walked through the results in the 2 trials, and we're going to share what we have posted on clinicaltrials.gov now.

We move to the next slide, please. So we have submitted data to clinicaltrials.gov where the study was registered. And according to their requirements, data should be entered within 1 year of study completion. These data were recently entered, and we saw them uploaded online just the other day. They are still in QC review, but based on their availability to the public, we felt it was important to share our interpretation of the data, or what we believe they mean already now. And this means that if you go to the clinicaltrials.gov site, you will see a lot of queries. These are related to the format and the way we've presented the patient groups. These are being reviewed. So there will be some small changes, but not to the actual data on clinicaltrials.gov.

And I think it's important to mention that what you see on clinicaltrials.gov are not yet peer-reviewed data. They're QC'ed and according to the statistical analysis plan. So we believe in them, but there hasn't been any peer review. The results do not guarantee regulatory approval per se, and they may be revised for publication if the editor of the journal or the peer review process leads to requirements or requests of data to be presented in another manner. And the same goes for the FDA. They may ask us to do the analysis of the data in another way in subgroups or stratification and so on, and that may lead to minor changes. But in essence, I believe that the data you can see there are the main results for these studies.

Another thing to mention is that there are different populations -- study populations that contribute to different analysis. We have the so-called intent-to-treat population. That's all patients that have been randomized. So the run-in patients is not included in that grouping. And that is the most fair way to compare randomized study groups using the intent-to-treat population. And then we have the safety population, and that includes the run-in patients and all patients that received any study drug. So this is to describe the safety profile of the drug when it comes to adverse events.

Move on to the next slide, please. So now we're going to go through the results with you, what's been posted. So these are from the clinicaltrials.gov, these tables. So first, the percentage of time at target station level according to the RAS scale. In INSPiRE-ICU 1, noninferiority was confirmed, and we did a number of sensitivity analyses and supplementary analyses to assess the robustness of the data and all of these analyses demonstrated noninferiority.

Move to the next slide, please. The same goes for INSPiRE-ICU 2. So the point estimates are slightly higher in both groups, but they're very similar between -- if you compare isoflurane with propofol, the percentage of time between RAS minus 1 and minus 4, and non-inferiority confirmed in all analyses. So we feel very confident that we've been able to demonstrate noninferiority in this primary endpoint.

Next slide, please. Looking at opioid dosing during sedation, our first key secondary endpoint. This was measured as the fentanyl equivalent dose versus baseline, standardizing all opioids into fentanyl equivalents. Looking at the change from baseline, what we saw was -- and this is what we were hoping for that isoflurane would demonstrate -- would be able to demonstrate a reduction of opioids versus baseline that was greater than propofol with potential reduction or potential increase. And that was the case both for INSPiRE-ICU 1 and INSPiRE-ICU 2.

And transforming this -- the reduction in fentanyl equivalents into percent reduction from baseline, INSPiRE-ICU 1 showed a 31% reduction of opioid dosing in fentanyl equivalents per hour versus baseline, and INSPiRE-ICU 2, a reduction of 37% versus baseline. And this is to be compared with a 29% reduction or difference between isoflurane and propofol in the Sedaconda study, SED001. So quite consistent reductions if you compare. If you consider propofol during sedation to be similar to the baseline, you can say that it's around -- it appears that in adults, it's about 30% dose reduction of opioids using isoflurane versus propofol.

Next slide, please. Now we come to time to wake up after sedation. This was the time from stopping study drug until patients reached the wake state of RAS 0 or higher, meaning being slightly distressed. And looking at the values, you can see they are low in both groups in both studies. The median values are slightly lower for isoflurane compared to propofol. And I think what's worth noting here is that in the 2 studies, isoflurane performs very similarly with an interquartile range from low numbers up to 45 minutes in INSPiRE-ICU 1 and up to 50 minutes in INSPiRE-ICU 2. And this, I would say, is consistent with all studies looking at wake up after isoflurane sedation, meaning that the vast majority of patients have woken up within 1 hour. And we'll come back a little bit to that when it comes to why this is important, even though there's no statistical significant difference in any of these 2 studies versus propofol.

Next slide, please. Looking at cognitive recovery 60 minutes after sedation, the CAM-ICU-7 tool was used, and we can see that in INSPiRE-ICU 1, the distribution of patients with regard to their cognitive function at 60 minutes is in favor of isoflurane in INSPiRE-ICU 1 and in favor of propofol in INSPiRE-ICU 2. Once again, isoflurane is relatively consistent. If you look at the actual percentages of time -- sorry, percentage of patients in the respective groups, you can see that about half of the patients are very lucid 1 hour after end of sedation and about one-quarter of them are fairly appropriate, but have mild or moderate delirium and it was 1/4, 20% in the first study and 29% in the second, that have more delirium at 1 hour after. So in all, if you were to pull these data, you'd have almost identical values for isoflurane and propofol 60 minutes after sedation in this controlled design that the study implies.

Next slide, please. Spontaneous breathing during sedation. This was a bit interesting differences between the studies. In the first study, there was no difference, very similar values, looking at assessments done every 4 hours, looking at spontaneous breathing efforts. And in the second study, we could see a significant difference in favor of isoflurane, which is similar to what we found in the Sedaconda study. So a higher proportion of time with spontaneous breathing efforts.

Next slide, please. We had a number of other secondary and exploratory endpoints that I would like to highlight today that carry importance. All of these outcomes, you could say, are classical endpoints in interventional studies in the ICU, where you could say that they relate to safety in some aspect when it comes to sedative treatment. So let's look at the results from these endpoints. And these were never sort of intended to be claims in our label. They are way beyond the key second endpoints and not included in the multiplicity adjustment, but they're still valuable. They provide valuable information when it comes to approvability of the therapy and the tolerability of the therapy. Now looking at the ventilator-free days, we can see that in INSPiRE-ICU 1, there was a difference of 2.1 days in favor of isoflurane. And looking at INSPiRE-ICU 2, the point estimate was the same for ventilator-free days.

Next slide, please. And we have ICU-free days. Here, we could see positive trends in both studies, not statistically significant, but a 1.7-day increase in ICU-free days in INSPiRE-ICU 1 and 0.6 ICU-free days more in INSPiRE-ICU 2. And both ventilator-free and ICU-free days related to being alive and having the good outcome. So ventilator-free days implies that you are alive and off mechanical ventilation, and ICU days means that you are alive and out of the ICU. So it both has a patient-centered outcome, but also an ICU sort of health economic aspect.

Next slide, please. Looking at the 30-day mortality, we could see that in both studies there was a 5% difference in mortality at 30 days in favor of isoflurane, which, of course, is very reassuring if some of you may remember the recent discussions that we had on the SESAR study using sevoflurane. And these results for isoflurane are contrast to those results.

And we can move to the next slide, please. And then looking at the 3- and 6-month mortality, similar to the 30-day mortality, there is a difference, not statistically significant, but clinically relevant, I would say, for both studies at both 3 months post randomization and 6 months post randomization with 3% difference at 6 months for INSPiRE-ICU 1 and 10% difference at 6 months for INSPiRE-ICU 2.

Next slide, please. Looking at the serious adverse events, which are the most important adverse events when it comes to the tolerability of a therapy, we could see a slightly higher percentage of patients in INSPiRE-ICU 1 with isoflurane that had serious adverse events, but significantly lower percentage in INSPiRE-ICU 2. And looking at the pooled results, overall, the percentage is lower for isoflurane patients, which is very reassuring, I would say, for this new therapy in the U.S. setting.

Next slide. So just a little bit about the first key secondary endpoint, the one we chose to have as our first key secondary endpoint in the sequential testing that is one way to manage a multiplicity of multiple testing. Opioids are used a lot in the ICU and actually used more and more over the last decade. One of the reasons is that physicians want to avoid the negative effects of intravenous sedatives. So an algo sedation has become something very popular in the last 2 decades, I would say.

What has been found, though, is that opioids also have certain problems related to the dose. Some of them are well known, for example, gut immobility in respect to depression. What is becoming more and more recognized is that opioids also contribute to delirium. And in some recent studies, it was demonstrated that among patients receiving more than 24 hours of opioid infusions during mechanical ventilation, almost 1/3 of these patients suffered from opioids associated withdrawal syndrome. This is well known in pediatrics, but it's becoming more acknowledged also in adults.

And importantly, there's also a dose-dependent persistent opioid use. And this has been demonstrated very elegantly in a publication, a very recent publication from Myers et al., looking at over 6,000 patients in Northern California that were receiving mechanical ventilation. They looked at the median hourly fentanyl dose and split the patients into 4 groups, no opioids, a little bit, a little bit more, and very high dose of opioids per hour, the fentanyl equivalent similar to what we demonstrated reduction of with isoflurane.

And they found that the higher median hourly fentanyl dose patients received, the more likely they were to have a filled opioid prescription after hospital discharge. And this is in a cohort of 6,000 patients, nonsurgical patients, meaning that there shouldn't really be sort of a surgical reason for them to need opioids after hospital discharge. About half of the patients had filled opioid prescription after leaving the hospital. And then there's persistent opioid use, which was found in about 25% of these patients, and this was also associated with a higher dose of opioids. So this tells us that opioid dose is correlated -- opioid dose during mechanical ventilation, which is exactly what we imagine is correlated with the higher likelihood of opioid use post-hospital discharge. And this, I think, makes an opioid-reducing sedative very, very attractive.

Next slide, please. So summarizing the results, we've demonstrated noninferiority for isoflurane with regard to percentage of time at target sedation level; a substantial opioid reduction in both of our trials, which has confirmed in our European trial and also in our pediatric trial; nonsignificant but clinically meaningful mortality differences in favor of isoflurane; and positive trends for 30-day outcomes, including ICU-free days. And ICU-free days were also higher in our German study in SED001, and that makes pooled analysis very interesting from a health economic perspective, and that's sort of beyond the label. That will be an important aspect of our work in implementing this in the U.S. And finally, I would like to say that the U.S. Prescribing Information, the USPI, will be informed not only by the results from our individual studies, but also from the pooled results and also from current information for isoflurane and published studies.

And if we move to next slide, the U.S. Prescribing Information for our therapy will be based on INSPiRE-ICU 1, INSPiRE-ICU 2, from the pooled analysis of these 2 studies, and the pooled analysis, including SED001 that the FDA requested. But also with the application we have, this 505(b)(2) application, we can leverage information from available publications. And to date, there are over 200 publications on inhaled isoflurane for ICU sedation available. And they tell more of the story than only our own studies. Also, there is an existing isoflurane label, which we expected to follow to the extent where it is plausible that same effects are valid also for ICU sedation. So also here, information can and will be leveraged in our application when it comes to the USPI. And finally, there are nonclinical studies that describe some features of isoflurane that are not demonstrated or have not been analyzed in our own trials. And these publications include pharmacological effects of both pharmacodynamics and pharmacokinetics of isoflurane. So there are many sources of information that will feed into our USPI draft.

Next slide, just to give some examples of information that we can draw from other documents than our own clinical studies and that may be considered for the USPI. Supporting studies, for example, include patient categories that we did not include in our studies. The reason we didn't include these patients in our studies, although we believe that they could benefit from isoflurane, is that some of our endpoints would not be measurable in these patients. For example, neurocritical care patients that need deep sedation might not be suited to target RAS minus 1 to minus 4, the same for post cardiac arrest patients, that's epilepticus patients, et cetera. These patient groups that are listed here are not excluded from our expanded access protocol, which indicates that the FDA do not see the lack of these patients in our own trials to imply that they could not be considered for inhaled sedation. Also, prolonged use beyond the study duration in our pivotal trials. There are over 20 publications about patients receiving treatment for several days and weeks. And that information we will also provide to the FDA and hope that may impact our USPI positively.

Looking at the isoflurane USPI for anesthesia, there are some clinical effects described there, such as induction of and recovery from isoflurane anesthesia are rapid. This is information that needs to be rephrased if it's to be used for sedation, but we believe that the data that we have for our own therapy in our clinical trials and also in the supporting studies do support this statement for sedation. And, of course, that will be an issue to discuss with the FDA if they agree with us, but we believe that we have data to support the same features for sedation as are known already for anesthesia in the last 40 years. And then there's a statement such as isoflurane undergoes minimal biotransformation in man. It sounds very complex. But what it really means is that isoflurane is not metabolized to any significant extent. It's eliminated by exhalation, which, of course, means that you do not need to have good renal hepatic function to eliminate the drug. And those are unique pharmacological features of isoflurane that we believe are part of the explanation behind the very short -- rapid wake-up times.

Next slide, please. So what remains for us now to do when it comes to the U.S., from a regulatory and medical perspective is to pool the data from the 3 studies and analyze them for our NDA to complete the nonclinical part of the dossier, put together these integrated summaries of efficacy and safety and the clinical overview and draft the USPI and submit all these data together with all the other parts of the dossier in Q1 2026. In parallel, we'll be preparing the results for publication in peer-reviewed journals. And we are also working, as you know, on the expanded access program for difficult-to-sedate patients, where we're currently working with the contracting and IRB aspects and hope to initiate in the fall.

Next slide. On the next slide is nothing. So questions, I guess, would be the next slide.

[Operator Instructions] And the first question here is from Filip Wiberg from Pareto Securities.

Can you hear me well?

Yes.

I've got a few questions here. Perhaps just starting with a general one. So what were your expectations ahead of this in terms of statistical power? So what were your expectations in terms of the endpoints that you expected to see significance? You talked a lot about you place these T1s in a sequential order with opioid usage in top, but did you have an expectation for all of them to meet statistical significance?

I would say we had hope for at least a couple or 3 for sure. We have experienced from wake-up times in our German study comparing with propofol. The scenario where you run this type of clinical trial with close titration of sedation with 2-hourly control of sedation depth is very far from daily practice, and it implies much tighter control, and also propofol is the most short-acting full range sedative available. And with daily wake-up tests, which are standard, and with the 2-hourly control of RAS, we were not very surprised to see that the differences were not so great. The same applied actually for SED001. So I think that's one of the reasons why we did not place that as #1, even though we see that as a very strong sort of differentiator between isoflurane and IV sedation.

If you go out in the real world and you look at patients sedated with propofol, there are a significant proportion of patients that are sedated a little bit deeper than prescribed. That's actually the general pattern in the ICU that patients end up being deeper than intended, and there's lots of literature on this. A proportion of these patients end up taking hours and sometimes even days to wake up. And I think that's the clinical reality if you interview an ICU physician if they've had patients with propofol that don't wake up, and they go for CT scans and they have neurology exams, et cetera, and then finally, they wake up. That is the clinical reality.

That's not what you see in our trials because they are very strictly controlled. This also means that it's harder for us in that context to show a difference. So we do see short wake-up times. We do see that our therapy is very predictable in terms of waking up. There's always a small tail of patients that will not wake up because they have encephalopathy, sepsis, et cetera. And that will always be the case. But I'd still say that with our therapy, if you stop our therapy, the drug is out, so you know, after 1 hour, after 2 hours, that if the patient does not wake up, it's not the sedative that's causing it.

With the other drugs, no ICU physician who sedated someone with propofol for a few days would feel confident to say that, and they would end up going for different exams, which is an extra cost, it's an extra staffing, resource, and a risk for the patient. Every transport of an intubated ICU patient is a risk. So even though we can't make a claim that we are better than propofol in our trials, I believe that if we are able to have a label that's similar to our European label, where we speak about patients waking up within 60 minutes typically, that's a kind of claim that resonates very well with clinicians. If you say, here's an ICU sedative where you wake up within 60 minutes, typically because of the isolation and the lack of need to metabolize the drug, that will resonate very well.

So just to answer your question, opioids is something that we have seen in our previous studies, and we feel is very important because of sort of the negative effects of opioids. So we're very happy that, that endpoint came out. Had we seen a shorter wake-up time, we don't think -- we had not expected it to be massive, the difference, based on what we know from our first German study. When it comes to CAM-ICU-7, sort of waking up in the 60 minutes after end of sedation, I think we would have believed that we would have seen a difference in favor of isoflurane. Now we saw that in one study and not in the other study.

Overall, I think that the percentage of patients that are not cognitively sort of in the best shape is still relatively low. It's about 20% to 30%. But we would have hoped that would have been significant, but it's not a deal breaker in our opinion. And as I mentioned, all the other endpoints that you see listed on clinicaltrials.gov, they were never -- they were not positioned to be able to form a claim unless there was a huge difference in both studies. They are not controlled with multiplicity management, which the 4 key secondary endpoints are with the sequential testing, but they are important to inform the sort of the decision to approve our therapy or not. And the fact that we do better or similar to propofol is a strength in our opinion. So I would say overall, we're very happy with the results, and we feel confident that we have a case when we work now with the dossier.

Okay. So just to make it clear, you think that the wake-up time for propofol in these trials here were significantly shorter than it is in the real world. Is that a correct interpretation?

Yes.

Okay. When you go through the results, it's quite a big difference in the results between the studies. If you look at the absolute values for the wake-up time, for instance, it differs quite a bit between the studies and also the p values and all of that. So is that just random factors? Or is there anything else to explain that?

That's a very good question. We have a few different explanations for that, none of which are sort of we can draw super strong conclusions, but we had slightly different -- so the ICUs obviously were different. So we had a little bit more medical patients, medical ICUs, different PIs, different constellations of PIs at slightly different dosing. So propofol was dosed lower in the INSPiRE-ICU 2 study than it was in INSPiRE-ICU 1 study. So more surgical anesthesia ICUs in the first study than in the second study. Patient case mix was mainly medical surgical. That was slightly more medical...

There was a slight lag in -- can you still hear us?

Yes. No, it's fine.

Something happened here. We are going to turn off our Bluetooth on our phone, sorry.

Yes. So the INSPiRE-ICU 2, during the course of the studies, we had sort of training and retraining. And one of the things that we did retraining on when we had done about half of the patients in the first study, but less than 1/3 in the second study was related to how the information about the blinded RAS was relayed to the study teams and -- sorry, from the study teams to the clinical bedside team. And I think both a higher percentage of time at target in the second study and also the dosing and post probably also the wake-up times in both groups, including the propofol group, was related to additional training about sort of strictly sticking to the protocol, relaying information from the blinded assessor to the clinical teams. And this may have led to that they perform better in general. And we know today that IV sedation can work almost as good, I would say, as isoflurane sedation if you put a lot of effort to it.

Ever since the -- 2000 was the year when the daily wake-up test study published in the New England Journal of Medicine, John Kress demonstrated that if you do a daily stop of IV sedation, you cut the time on the vent by a few days and you cut the time in the ICU by several days. That was in year 2000. Since then, there have been multiple studies showing that if you give a lot of attention to the IV sedation you're giving, you keep on doing daily wake-up tests, you go for lighter sedation, et cetera, you do combined wake-up tests, breathing tests, you get better outcomes.

These studies all are about managing the issues with accumulation of IV sedation. And in that first study in the year 2000 from John Kress, they didn't only look at benzodiazepine, they looked at propofol as well, and they found the same effect when you compare the propofol group with patients that had daily wake-up versus those that did not. So all of these efforts -- if you spend a lot and lot of time with your sedation with IV drugs, you could get relatively short wake-up times, but that's not how the reality looks like today. It's really difficult to devote so much time to sedation. And that's where I think isoflurane is a more forgiving drug. I think the supporting studies that are out there in the literature, they indicate that even when you sedate deeper, patients wake up quickly. I think they were more -- even they gave a lot of attention to this aspect in the second study.

Yes. Okay. All right. I just wanted to stay on the wake-up time for a bit, because opioid usage, all right, it's important. But from a hospital perspective in the U.S., for you to be able to sell to them, they have to see commercial case in that as well. So they need to be able to save some money. And based on the NICE guidance that you have, the cost saving comes from waking up faster and getting out of the ICU in a quicker manner then. So don't you see this as a big issue then that you cannot show that it's significantly faster wake-up in this U.S. trial here?

So the label has a section that's about the clinical trials where you compare the 2 therapies that have been tested in the study. But there's also a part that's called clinical pharmacology. And the clinical pharmacology section, that's where we currently have described the pharmacokinetics and pharmacodynamics of our therapy. And in the European label, as I mentioned, we have a statement about typical wake-up time being within 1 hour. If we were to come anywhere near that in our USPI, I believe that the available data on isoflurane sedation, and that's not only our own studies, but other studies that have been performed looking at wake-up times, is quite compelling.

And when it comes to NICE guidelines, that's sort of related partly to the wake-up time, but also the downstream effects of those short wake-up times, meaning ICU-free days. And as I mentioned, if you look at the results from the Sedaconda study and from the 2 INSPiRE studies, you have roughly 1 ICU-free day more with using isoflurane versus propofol. And I think if that's something that we can convert into a sort of health economic message, I think that, that will also be compelling. So if you go into an ICU and you say, this is a therapy with which your patient will wake up within 1 hour typically. And if they don't, then you have reasons to believe that something else is going on with your patient. That is a message that will resonate better than talking about 30 minutes shorter time than with propofol, because that's not the typical pattern when you use propofol, as I mentioned.

This is hard to describe to a non-ICU physician or non-ICU nurse, but this is truly the case that the typical comment when someone doesn't wake up after 4 or 5 hours, "oh, she's old, she needs time," or "he's very sick, he needs time". And with our drug, I would say that's not the case. Now that's not going to be in the label, what I just said, but I think this waking up within 1 hour, if we have something about that in our label, I think that will be equally as strong as having a benefit of 20 or 30 minutes.

We're not in the operating room. In the operating room, 20 or 30 minutes is huge. We're now talking about the reliability of wake-up, meaning that when you stop the drug, you know that the patient should wake up normally. That translates into progression of care in that you can plan the wake-up time, so when you activate a patient, you have a nurse, you have a respiratory therapist, you have the physician there, you need to be prepared to reintubate this patient. If you have a therapy that consistently leads to patients waking up within 1 or 2 hours, you can assemble this team and they know that they will have work to do and this patient will be activated.

Once you have a drug or therapy that do not give that reliable wake-up time, you may end up a full day patient not waking up. And what happens in the afternoon and evening, when you only have one physician left in the ICU, is that you resedate that patient and then you wait one more day until you extubate them. So now I feel we're getting into a lot of sort of medical details about sort of how the messaging around this therapy. But I don't believe that a 1 hour or 30 minutes mean value difference in wake-up time would be most important when it comes to endpoint. It would have been great if we would have seen that. But our expectations were not super high based on what we saw in SED001. We're very happy that the majority of patients, so as I said, the interquartile range stretches up to 50 minutes in INSPiRE-ICU 2 and 45 minutes in INSPiRE-ICU 1. And those values in themselves are -- they have a strong message in my opinion.

I'll limit myself to just one more question, if that's right. Just now you have reported the study results for the separate trials. So the question is more, what do you expect to see once -- once you pool them together, the statistical power will go up. So do you believe this could tilt some of the endpoints where you have seen a trend, where you could tilt them into statistical significance?

Yes. So when it comes to the label, I don't think very much will change, because we have noninferiority in both studies, and we have that in the SED001 study. So those estimates, even if pooled, will not -- there will be no change. When it comes to opioids, we see a reduction in our German study. We see it in the 2 U.S. studies. Same thing applies there. It will be more that there will be -- if we align with the FDA on pooled data being presented rather than individual studies in the label, then you'll simply have one estimate for opioid reduction in the label for the combined studies, either the 2 U.S. studies or the 2 U.S. studies plus the German study, and it will be somewhere in the range of 30%. So that wouldn't change much.

When it comes to wake-up times, as I was alluding to, the differences are very, very small. We did not make it in any of the studies to statistical significance. So we don't expect that to be anything that will make it into the label. As I said, these are all review questions. And when it comes to the other endpoints, the long-term endpoints such as mortality, 30-day ICU-free days, ventilator-free days, those endpoints are not analyzed with any multiplicity correction. So we don't believe strongly that the FDA would say that we could now bring them into the label just because they became statistically significant. That's typically not what you'd expect.

We might get some information there related to safety, for example, maybe mortality, but that will be a review question, whether the FDA agree that, that's an important safety variable to include in the label. So I think it's rather on the other aspects of this sort of -- if you think about the information that we get from these studies, it's not only for the label, it's also for reimbursement, et cetera, market access. And there, I think that pooled data may carry greater significance.

Okay. But -- so you haven't decided with the FDA whether the label will include pooled data or the separate study results?

No. Exactly. So that's a typical question that will be either during the pre-NDA meeting or in the review phase that we -- depending on the guidance that we've read and the advice that we'll get, we'll propose pooled data or separate study data. And I'm personally eying to pooled data because it's easier for a prescriber to read a point estimate that's based on a big cohort of patients than to look at 2 different study results and try to figure out which one should I believe for my patients. But that's my personal preference. It has to be the FDA need to agree with us that, that would be an appropriate strategy.

Just to build on that, Filip, I mean there's 2 slightly separate -- or actually completely separate questions here, right? One is, are these data good enough to get approval? So that's an FDA decision. And I'm sure in your model, when you look at Sedana Medical's value, it makes a huge difference whether there is a U.S. business or whether there is not a U.S. business. And then the second question is, based on these data, will we find enough hooks for differentiation so we can, together with good commercial execution, have a successful launch?

And for the first question, I think that the way the FDA would look at these data is, okay, primary endpoint met, safety in line with expectations, opioid reduction proven, everything else either trending in our favor or no difference. So from an FDA approval perspective, we don't see any showstoppers in these data, right? So there's never a guarantee, but we feel quite confident that based on the clinical data, at least this therapy is approvable.

Now the second question, will we find differentiation? I think this is where your question around pooled data and further analysis will be extremely relevant. And the good news is, when it comes to the more health economic arguments, here it's not only dependent on the claims that you will be able to make in the label, because you're dealing with purchasing organizations, so you're dealing with purchasing departments in the hospital, and they are open to also look at something like the NICE guidance. So they would look at European data. Or -- I mean, if you just look at the ICU-free days and now we had 1.7 days difference in one U.S. study, 0.6 in the other. We had 1.3 in the European one also in our favor, and then 3.5 days difference in our favor in the post hoc analysis. So all of these go in our favor. So if you imagine a publication that is pooling all of these data, that could make a quite convincing argument towards somebody who's making a purchasing decision in a hospital, even though the label maybe wouldn't say you can expect your patient to leave the hospital X days earlier.

Okay. Yes. That's a very good answer. I'll stop there and let someone else ask some questions as well.

We will now carry on with some questions that have been sent into us. 470 patients randomized across both studies. Any thoughts to be added regarding the amount of patients as basis for the secondary endpoint readout?

So is this related to -- just trying to figure out if this is related to sort of power? So there are no -- we have not performed power analysis looking at the 470 patients and the key secondary endpoints, nor to the other endpoints. The individual studies were powered based on assumptions related to the primary endpoint. That answers the question.

Thank you. Do you think it's possible to show 1-day reduction in ICU stay based on the data at hand today? And how many ICU days are there in total to put into perspective here?

So that I think will be too early to answer. But as I was alluding to, we do see that the ICU-free days are more, even though not significant in all 3 adult studies that we were discussing. And I think that will be sort of a question related to what Johannes was describing from a reimbursement perspective, whether that's considered 1 ICU-free day. In my opinion, it's a good outcome, 1 ICU-free day, and 1 day alive and outside the ICU. I think that would resonate well both with payers and with patients and families. But that will remain to be seen whether they agree with us.

Yes. I think, again, there's the question of statistical significance, and we will see what the pooling data shows us, but there's also the relevance question, right? So we have now 4 data points, again, ICU 1, ICU 2, the European study, and the post hoc analysis based on the European study, all pointing in the same direction that inhaled sedation with isoflurane is reducing the ICU length of stay and you have more ICU-free days. And just intuitively, even if it's 1 day difference, that's a pretty meaningful outcome. First of all, financially because every ICU patient costs a couple of thousand dollars every day. So it's the most expensive place in the hospital to treat the patient. So if you can cut that down by 1 day, it makes a big difference. And also just intuitively, if you think about your -- now these patients have only been exposed to isoflurane for 2 days, right? And otherwise, they got propofol. So only this 2-day difference in change of sedative leads to a day in additional ICU-free days. That is a quite meaningful outcome.

Thank you. What will be the price of Sedona therapy versus standard of care in the U.S.?

Yes, that question is too early to answer. What I can say is, in Europe, we are priced a bit higher than the intravenous sedatives. The reason being that we also bring better patient outcomes. And I'm expecting the same pattern in the U.S. as well, but it's too early to give a specific number.

Thank you. If we look at patients under the early access program, difficult to sedate patients, what share of the total amount of patients are those in the U.S.?

It's a good question. The definition we have agreed upon with the FDA is a unique definition in that it's not a definition that is universal. There's no universal definition of difficult state. And that means that you can rely on available studies that describe the percentage of patients that are difficult state in the studies that are available, not from the U.S. specifically, but from Europe. We are talking about somewhere in the range of 15% to 25% of all mechanically ventilated patients. But as I mentioned, that's based on a definition of -- for example, Spanish Association for Critical Care have their own definition, which is not too different, but it's not identical to the one we have.

Thank you. Does this data impact your ambitions to launch in the U.S., or at least impacting your plans on how to launch in the U.S.?

No. So the strategy is still very intact. I think what has changed is that it's becoming a bit more real, because the likelihood of the clinical data being approvable has increased because there's nothing that is going against us here. And again, we have a few things in our favor as well. So we are continuing to prepare for a launch that is going to be focused on the great network that we already have in the clinical trial sites, and we will use those as our lighthouse accounts and build sales territories around them. And I think the level of enthusiasm that we're getting, you saw a lot of happy faces on that picture that Peter was showing earlier, gives us the confidence that we have a good enough support network to start a successful launch ourselves.

267/5,000 there. How does the failure to demonstrate a reduction in ICU stays affect for insurance companies' ability to include sedation among their treatments?

Yes. I think we've covered that already. So there's no failure of showing ICU length of stay. There's a 1-day difference that we see. Let's see how that changes when we pool the data and combine it with the European data. But from a hospital purchasing perspective, that is a meaningful difference. So I wouldn't call that a failure.

ICU 3 days differs slightly from the European study. Why do you think that is?

The data is actually quite close. So in Europe, we had 1.3 days difference. And then in the ICU 3 days for the U.S., we had 1.7 and 0.6, respectively. So I think these results can be seen as quite consistently. There's also a post hoc analysis where the difference was greater, where we are comparing patients that were exposed to either propofol and isoflurane for a longer period of time. So that explains the bigger difference here in terms of days. But importantly, all trends are in the same direction. So it's actually very consistent results.

Opioid misusage generally does not stem from patients being admitted to opioids intravenously at an ICU. Considering this, do you think the statistically significant data on the opioid secondary endpoint carries any weight from a commercial standpoint?

Well, so I beg to differ. The biggest study examining this was the one I referred to, 6,000 patients in a very well-controlled data system. The Kaiser Permanente in Northern California demonstrated a clear correlation between the dose of opioids in fentanyl equivalents given during mechanical ventilation and the likelihood of filling an opioid prescription after discharge and also a persistent opioid use in the first year. So there is a clear correlation between what we do in terms of opioid use in the ICU, and later misuse.

Thank you. Moving on to the last question here. Is the FDA Fast Track designation now at risk of being withdrawn considering no meaningful data could be statistically proven?

I beg to differ again. The primary endpoint has been demonstrated to be -- we've met the primary endpoint. And the most important key secondary endpoint, opioid use, has been shown to be significantly lower in both studies and in line with previous studies, 50% reduction in the pediatric study, 30% -- 29% reduction in adult study. So I would say those are really meaningful differences that we're happy to have found and that we believe strengthen the case for inhaled sedation.

Thank you so much. That was all the questions we had. So thank you so much for presenting here today and answering all questions. And thank you all for tuning in. I wish you a pleasant day.

Thank you.

Thanks a lot. Have a nice day.