Good morning, everybody, and thank you for joining us in this conference call covering some aspects of, from the study that we sent out the press release to last Friday, the Connection study. We are three people here from IBT. It's Peter Rothschild. You can say hello and tell the people- Hello who you are. I'm chairman of IBT, and also a major investor in IBT. Thank you. We also have our Chief Medical Officer, Jonas, Professor Jonas Rastad. Could you make yourself known, please? Now you're on mute. Does this work better? Yes. Thank you. I'm Jonas Rastad, and I've been with the company for six, seven years or something like that. My background is general surgery. I'm a professor emeritus of surgery in Uppsala. Spent almost 10 years with Staffan and others in AstraZeneca working on drug development, and then went on to become CEO of a hospital in Sweden, and then having the same role in the region of Västerbotten and Region Skåne. I'm now retired and working on this project only, and some others in the company. Thank you. Thank you, Jonas. So- Thank you. We're very happy to see 192 people currently on the call. We will try to move quickly or at the right speed through the results, and that Jonas is gonna present, and then we're gonna touch upon the possibilities to register a drug and also the IBT plans going forward. Then we would like to leave as much time as we can for you to ask any questions, and we will try to provide you with the best answers we can come up with. That's today's game plan. Before we start, I'd like you to. When you would like to ask a question, you can raise your hand, or you can simply unmute yourself, and then you ask the questions when we come to the question and answer. So I suggest we start by looking into the data that we have of. So Jonas, please present. Thank you, Staffan. We were ecstatic as well as disappointed, you know, a couple of days ago, when the unblinded results finally came in. We worked very hard for many years on this pretty challenging study, to be honest. We saw the primary endpoints, as you are aware, of both of them not reaching statistical significance. The first one, and the one we powered the study on, which was confirmed NEC, which actually means intestinal necrosis in the premature infant, either demonstrated by independent adjudication of abdominal X-rays that the investigator would gather because the infant developed some kind of clinical signs of NEC or necrotizing enterocolitis confirmed by surgery or autopsy. We did not reach statistical significance, as you're aware of. We had a relative risk of 0.86, which means a 14% risk reduction of the treated versus the placebo patients in this examination, with a p- value of 0.24. We wanted something like 0.04, and this was not significant. The other primary endpoint, which is a feeding endpoint, which we believe is very important to the development of the premature infant. The gut drives a lot of well-being as well as potentials for complications and diseases in these infants. It's underdeveloped and needs enteral feeding to develop in a normal way. That endpoint, which is a very strict definition of sustained feeding tolerance, that means that the infant must maintain enteral feeding above 120 mL per kilo per day, as well as receiving no parenteral support in terms of macronutrients, and must grow above an average of 10 g per kilo per day during a consecutive time period of 10 days. And the 10 day is the invention here, I would say, which actually makes this very strict. And also on this endpoint, we did not reach the statistical significance we wanted. It was 0.06, which is close, but sorry, 0.07, which was close, but nevertheless good enough. We were disappointed on these two outcomes. We came to the secondary endpoints of the study, which, you know, are a couple of them, and in particular, we're very, very excited on the effect on all-cause mortality. I'm uncertain how well acquainted everybody around this call is around what that means. That is the hardest endpoint of all to reach within a clinical trial. That is one of the reasons we made a second endpoint. On the other hand, it is one of the absolutely most indisputable endpoints you can have, 'cause there is no question about whether an infant dies or not. This is striking, and as you maybe saw on the press release, we have a significance of 0.036 here, with a relative risk of 0.73, which is a risk reduction of 17%, and everybody can calculate what that means. There was a reduced risk with this potential drug in terms of deaths is real and clinically relevant. Thank you. Thank you, Jonas. Maybe I can ask a question, and did you say 17% risk reduction? I think you meant 27%. You had- Oh ... 17. It's difficult to, you know- Yeah ... subtract 100 to 73, so I agree, 27. Sorry. Thank you. Thank you. Should I repeat? No, no. We're very excited. No, thank you so much. You have now touched upon the efficacy, endpoints. I wonder if you would come and talk about the safety we see. I mean, do we see any safety concerns? Have you seen any problems, for example, with sepsis? We know that bacteria can cause sepsis, and therefore, did you observe any of that in your trial? I know the answer, but I'm just- I'm sure you do. We discussed this for a couple of days. That is actually not a surprise, but a striking finding. However, you know, any way we cut the data, we don't see a safety signal, as we call it. That is a concern in terms of something happening to a greater frequency, you know, a significantly greater frequency in the treated versus the placebo infants. And that particularly pertains to sepsis, which is bacteria occurring in the blood of the infant. That's been the concern of the FDA and other health authorities in terms of treatment with live bacteria. We never have ever seen any infant with Lactobacillus reuteri in the blood to start with, and we do not see an increased risk of sepsis or actually any other adverse event, serious or not, occurring in these infants. Very good. Thank you. We might come back to questions on the clinical trial, what we have seen and what we haven't seen, but let's push on in the agenda and talk about some possibilities about registering a drug, and I was thinking that I tackle that now, and I want to dive in and tell you what I believe is true from a couple of perspectives. The first perspective is the law. The law that regulates drugs in America and in Europe is very similar. The requirements are that the benefit-risk ratio or the balance between harm and good needs to be beneficial. If it's not the correct balance, that product should not be on the market, and this law is written to protect, if you're in America, the Americans, if you're in Sweden, the Swedes. As an ex-regulator, I've been sitting, conducting this judgment, is this beneficial enough to carry any particular risk? So what is important to know here is that we missed, or we didn't reach statistical significance on our primary endpoint, but there is nothing in the law in any country that I know of, that requires a regulator to consider p-values, okay? They will do, don't get me wrong, it's an important piece, but it's not breaking the rules if you do not consider p-values as your base for making your assessment. I think a second thing that is important to this puzzle is that our product, 9414, is addressing a true medical need. We're working in the intensive care unit, where the patients are placed in order to survive. If you take them out of that hospital, they die. That is the most, and Jonas, please correct me, you're the professor of medicine, but it's in a very intense situation, where you're trying to save the babies. And here, they grasp a lot of technology, a lot of knowledge is applied to just keep the baby alive for the next day or for the next week. That's the objective of that type of hospitalization. And we are walking in there to do something, to be beneficial, to help these babies survive. That's the whole intention with 9414. At the same time, we have, from day one, designed this product in a way that we can- it can be administered to the most vulnerable population on the planet. So you just heard Jonas say that we didn't see any safety signals, and we saw a reduction in mortality, death, which is exactly the target of our drug. Now, I also must say that when we designed this study, we sat down with regulators around the world, and we discussed the endpoints. And we discussed the possibility that it's very hard to measure in this very sick population, and that we have to select some endpoints, and we have to power on them, and we have to call them primary and secondary in this form. We have done so, and it is a fact that we see a striking effect on a secondary endpoint. I will be much happier, we will be on the paved path towards the market if we saw the primary endpoint delivery, but we see a fantastic effect size with statistical significance on the secondary and the hardest endpoint there is on the planet. So I think when you put these regulations together with the medical need, and on top, you look at the data we have obtained, safety, no translocation observed, we see trends on SFT and NEC, and we see the reduced mortality. It means that this is a fantastic drug that the professors and doctors out there wants to use. And therefore, I want to ask my friend, Peter, to continue this little call by talking a little bit about IBT's plans moving forward. Okay, thank you for that. And I can be really boring, because I can tell you basically they are not changing. We intend to register a drug. It will be a different pathway, different considerations, but we, as Staffan said, we know that the medical need is there. We know that we have hard data on death, and therefore, we think there is a good chance that we can register a drug, and we will continue the pathway. Meaning that we will also work with the CMC. We need to, the production, the manufacturing of the drug, meaning that we have to make commitments in various ways to be able to supply and provide FDA and other authorities with the right data also on the CMC. Mm. So it's not only the clinical data, we also need to have a full application with everything that is included there. And so from that point of view, I don't see that we... You know, our purpose is still the same. We want to save these babies. We want to continue to work, you know, pre-marketing work with key opinion leaders, and of course, with regulators around the world, and have them understand what we have done. And of course, there is always a risk, whatever you have done, that the drug will not be approved. It's difficult to say if it's, you know, 50% or 60% or 40%, I don't know. But in my judgment, and being also an investor in the company, I see that we have still very good possibilities to register a drug for this purpose, and if we are saving them, that's really what's, I suppose, for doctors and all the health professionals and parents; that's the important thing, and I think also that we have been very prudent with our financial situation, so we have luckily the means of continuing our work. We are not in any crisis and we have sufficient money to work basically on what we said that we would do, namely register the drug. Thank you, Peter. Are we ready for questions? I see that Christopher Uhde would like to. He has raised his hand. Let's move on into the question and answer session. Christopher, please. Thank you very much. A few questions if I may. In terms of the mortality benefit, are there any subgroups, excuse me, driving the mortality benefit, especially either stratification criteria or specific countries, and in particular, US, Germany, and Italy? And are there any where you see a detriment? I'm asking because of, obviously, it relates to likelihood of approval in different regions as well as reimbursement. Jonas? Yeah, yeah, thank you. Let's take them one by one, Christopher. You want to pick that up, Staffan? Yeah, I think you can comment on that, but remember that we want to not provide the different numbers in this call. But you can comment on it, please, Jonas, as if you see a difference or not, and so forth. I mean, we have worked very hard, and we see subgroups where the relative risk is substantially lower than in the U.S., but we need to work a bit more on this before we conclude. I think that's fair to say. We got the results for 2,150+ patients last week. I mean, it takes time to really go through the data, recalculate, use different statistical methods. So right now, I would prefer just to leave it at that. Okay. I would like to say that we have done preliminary tests looking at some of those whole groups, and we have not found any big differences, so forth. I think Professor Åstrand is more cautious in his answer, and I would say we haven't seen anything, and we have looked at regions to some extent. ... maybe one explanation also why we don't want to give or can give you too much information on data, is that this is, of course, we are intending to publish this. And, the journals that we want to be in, they don't allow us to publish a lot of data. So we have to be really basic here. We'll try to answer the questions anyway, but this is a consideration that we have to take. No, absolutely, I understand that, and I appreciate all the help you can give us. My next question is, again, so around secondary endpoint, days in hospital. Could you comment on whether that's been so reduced in the treatment group relative to placebo? And again, I'm asking because it's relevant to reimbursement. I think it's relevant to reimbursement, and as it looks right now, we're not too impressed by that endpoint in terms of what we see for our agent. So the answer is that we will publish the data, but it's not coming out as something very strong. Okay, and then the next question I have is, so in terms of, you know, post-hoc subgroup analysis, I mean, you've commented a little bit, but have you seen any subgroups with a detriment or that are driving the benefit? I can, I can answer that. We've been spending, and Jonas, you can correct me if I'm wrong, we've been spending three days together with the international experts trying to find something that would make us change our happy smile when we look at the mortality. And we could not find any, any reason not to keep on smiling. And also remember that the ultimate safety, the endpoint, not an adverse event, but the end of all our lives and everybody lives, when everything has gone bad, is to die. And we've been looking into the subgroups to see if there's a particular thing that drives the death, and that would be the explanation why we see what we see. But we cannot conclude anything on that, on those subgroup analysis. The only thing we can see is that it mechanistically all hangs together with the gut. So, for example, when we look at bleeding in the brain, IVH, it's called, in the medical term, we don't see brain bleeds as the reason why we see a difference between 9414 and placebo. So it has to do with the gut, and I've been showing many of you a very colorful picture where you see that why babies die from week two and so on. It's a blue and a very colorful picture I've used many, many, many times. And what we can see is that we see that we have a difference in the death that we think relate to the GI tract. I think, if I may add, one should also be realistic. If you have a significant outcome with a reasonable risk reduction, and you find a subgroup that's, you know, major one with a really improved outcome, you're gonna have a penalty on those not having this characteristic. So the evaluation is pretty, I think, critical here. We have subgroups, as Staffan alluded to, where we have an even stronger signal. But on the other hand, there is also then a proportion not having this characteristic and where you have a weaker signal, and that sort of is part of the game. Yeah. And then, thanks. And then in terms of, I guess, the mortality benefit and subgroups, I mean, do the 95% confidence intervals on the Mm ... yeah, overall secondary there, cross one? No. Are there any key subgroups that do? No. We are on the right- If you start on subgrouping, you will find those where the relative risk confidence interval passes one. Yes, but it's not, it occurs very rarely because the treatment effect then is so strong in the group having that characteristic, as I just alluded. Great. So just to repeat, the 95% confidence interval do not cross the magic number one. Okay. And then, in terms of the, this is, I guess, a question for... Well, why don't we start on next steps? Based on sort of the available data and assuming one way or another, IBP-9414 gets approved, what kind of label could you imagine getting? Will you try to get NEC and SFT on the label? Or would, you know, would you look at prematurity? What could you... 'Cause I guess mortality is unlikely. Let's just, well, let's say like this: We have, we'll discuss this further. The intention was to have NEC and SFT, and that has been discussed with several agencies. And now with the p-values for on those endpoints, we would like to discuss more with the agencies. But I want to highlight the fact that, for example, Curosurf, if you look at Curosurf's label in the United States of America, it says reduction of mortality. So if you look at the effect size observed for Curosurf, and you look at what we have seen, you can draw conclusions, and we should not rule out anything in terms of label. But that's something we will discuss with the authorities. Maybe you should clarify what Curosurf is, Staffan. Curosurf is a surfactant. I mean, if you- Could you elaborate a bit on the mechanism of action, please? Yeah. No, but Curosurf is a drug that was introduced some years ago, and that helps the baby to breathe in the beginning of life. And it's really important because it improves the survival, it reduced the mortality, and the doctors are using it everywhere to save the babies. And we would like to see something similar, but for the gut with our medicine. Okay, thanks. You mentioned that some of the sort of types of mortality are consistent with what would be sort of implicated, or where the gut is implicated. Do you have any sort of biomarkers that are kind of relating to mechanism of action that you know coming out of the study that also adds support to the inflammatory and sort of, well, gut health state? Yeah. I think we have to combine our different efforts here. We have a phase two study. We have also a lot of experience from this agent in humans and in animals, and I am sure that when you put all that together, it will tell you what you're looking for. We don't have, and we haven't assessed, and we don't have much bio data from this trial. This is the largest trial ever conducted, and we were focusing on getting very, I mean, strong data on how the baby behaved, how what was the safety was, and the efficacy. So this is not a mechanistically designed trial from the beginning. Okay. And then, my last question is for the, I guess, the main owner, since we have the luxury of having him on the call here. If a confirmatory trial were required, either post-marketing or pre-submission, would you be committed to contribute to funding of it based on what you've seen so far? Mm-hmm. A good question. I think it's worthwhile, yes. I do at this time with the information I have today, yes. Things, you know, we need to speak to authorities and find out, but what their views are. But my own opinion, which is not worth more than my opinion, is that this is still a very attractive investment case. So that's my take of it. Okay. That's all my questions for now. Thank you so much. Really appreciate it. Thank you, Christopher. Thank you. We're gonna move on, and we have David Dangour on the list. Please, David. You need to unmute yourself. Maybe we can unmute him. No, we can't. Okay, we hold David, and we move on to- Sorry, sorry. Here, David. Based on Christopher's questions and your answers, I understand that this question from mine is probably something you can't answer. But if you can show that the survivability of the babies that develop NEC is significant, that's almost, to me, like 90% success on endpoint one. Yes. I think. That's one question. Go ahead. Yeah. I think you're onto something there. There is, of course, we're calling it a trend, because we pre-specified what we would test according to the protocol and the statistical analysis plan. There are additional analysis you can perform, and there are things like you were alluding to here, Mr. Dangour, that I think is absolutely relevant, and we will look and see what can make a good argument. But I also want to be very clear here. The game is that you set up your primary endpoints, and you deliver on them. That's the normal situation in drug development. But to my point, there is nothing that prevents the regulator to look at the overall totality of the data available, looking at the safety, looking at the effects on this very hard input, mortality. I think it's that that is even more important than any observation on necrotizing enterocolitis. My second question, very quickly, is how long do you think it will take, not in the best case, but in a normal case, to get a drug registration? I think like this: if you look at the medical need that we address, and you look at the hard endpoint and the effect size and the P value for mortality, I don't want to speculate, but every day this drug is not being used, we know that we could save babies, if this was used in the intensive care unit. And that's something we're gonna discuss with everybody that wants to discuss it. How fast can we put this on the market? Because we're here to save the babies. We also have, like, Mr. Rothschild was saying, we need to get going, and we will get going with our production, so we are able to meet the demand from the market in the, hopefully, the near future. But I can't be more specific than that. I can also add that FDA, as you might know, have issued twice, I think, warning letters to sort of dietary supplement probiotics. It's pretty well known that they would like to have something approved. I think it works in our direction, that they would like to see something that has gone through the sort of regular testing and in terms of production and also clinical trials, so hopefully that will also mean that they have a positive attitude. Thank you. Thank you. Maybe I'd like to add to Mr. Dangour's question on causes of death, because the NEC death was mentioned. In some cases, you have a clear clinical diagnosis, but the specific or primary cause of death is often a clinical judgment rather than a truth. Thank you. Could we move on, please, with questions from Mr. Panigrahi? Grahi. Sorry for my pronunciation. Thank you. This is Pinaki Panigrahi. I'm at Georgetown University Medical Center in Dermatology. First of all, I have to congratulate you for to have completed this study. For somebody who has worked on probiotics and in neonates for, I don't know, a quarter century, I understand what all you have gone through, and it, it's a landmark thing that you have done. And more so, as we have heard from Peter and others, FDA definitely wants to see something like this, and so all kudos go to you. I have one or two questions. I mean, the mortality, as you said, that's the bottom line, and in neonates, especially, you cannot really do any study without having mortality as an outcome, because you may reduce something and be happy, but at the end, I mean, there have been instances also that overall mortality is increased. So that's not good, and as you said, we want to save babies. With that and with the excitement, I am interested in neonatal sepsis. I know there is no bacterial translocation, no lactobacillemia, but what about regular early-onset and late-onset sepsis? Did you see any effect on those? And then you have said that you haven't probably done the more biomarker things, so is it due to change in permeability, due to change in gut flora? Even if you haven't done those studies, have you saved samples, stool and urine types, samples, so that we can learn more? Antibiotic resistant acquisition of antibiotic-resistant bugs, you have an... I just saw on your website, I hadn't seen, you have another product which will reduce acquisition of antibiotic-resistant bugs. So all of them are good, good news to my ears, and so can you comment on sepsis first, and then on anything else that may be going on? Thank you. I will. Do you want to comment on sepsis, Jonas? And I can comment on the second question, please. Good. Yeah, early-onset sepsis is an exclusion criterion in entering into the study, so that's not been monitored. So infants with early-onset sepsis, born to mothers with chorioamnionitis, are not eligible for inclusion into the study, and this is within the first 48 hours. So mortality is actually quite low. It's in the 8% range, all in all. We exclude infants with in extremis, those with known chromosomal aberrations and whatnot, which means that this is. We needed infants with a high probability of surviving the study period, to in essence. So we are not studying an early-onset sepsis. In terms of late-onset sepsis, where we see no difference in active versus placebo, we cannot argue any treatment effect, but on the other hand, we don't see any increase either. This is not taking care of all the other infections that happens in the bloodstream. We have- At least, Staffan, maybe we should say, during this study period of up to 40± 7 days. Yes. I mean, that's fair to specify, I think. Yes. You did look at culture positive. Of course, to me, I want to look at culture positive sepsis, and then I would like to see gram-negative versus gram-positive sepsis. But some clinicians would still go by suspect sepsis, and that terminology is becoming much more cleaner day by day, and most people don't want to use it, and we are using less antibiotics. But with that, either way, you are saying that it hasn't changed. No ... any gram-negative or positive sepsis. We have not looked at specific agents, but we looked at clinical as well as culture positive late-onset, and we don't see any difference in that respect. Very good. Thank you. I must say that it's very important to say that this study was not designed to detect sepsis. This is only from a safety perspective, we have compared the different groups and see, and the behavior on the aspect of sepsis. So you don't, doctor, you don't have to worry about sepsis, but I don't think this is a sepsis treatment or a prevention of sepsis agent. Sure. Yeah. No, no, because I am interested in reducing sepsis, and we have done large trials using probiotics that, the largest trial we did, included about 4,500 babies. Not in the US, we couldn't do it with all NIH funding, but we did see reduction of late-onset sepsis, and those are all almost 100%, although we don't have any biomarkers, the mechanism, again, for the same reasons we couldn't do, is all pointing towards the GI tract and saying that, yes, the permeability and translocation of the other bugs, non-Lactobacillus bugs, are reduced- Mm-hmm -by when you give a good probiotic. So thank you. Thank you. Did we answer both your questions by that, or what was the other question? Yes, I- Mm-hmm. The other question was if you had any other biomarkers- Yes ... so that we could point towards mechanistic aspect of why it is reducing, but, The answer to that is that we have, for example, stool samples that we have from our phase two study that we have conducted. I think it's very interesting to look at the data and the observations we have and to make, you know, to write down what we see, but we haven't had the time to do that. We got the results, you know, a few hours ago, it feels like, but we are here to discuss the topic of, you know, the results from that perspective. So thank you for your question. Let's move on. We have Jonas Erlandsson. Please. Yes, hello. I hope you can hear me. I have maybe two questions. The first one is, and I'm not very into this area, so maybe my questions are totally wrong, but please answer them, and it's, why was mortality a secondary endpoint rather than a primary endpoint? Is it because of the market potential, or is it like it's too vague? Yeah. Thank you, Jonas. I think this is a very, very good question. This is the question I would like to have asked, have another different answer to, but I don't. The fact is that we didn't have any data at the time of starting this trial back in 2019. We didn't have any survival data. We didn't have any risk reduction on mortality data available, and therefore, it's very hard to power and say, "We will reduce death. Mm. So what we had was we had convincing data on necrotizing enterocolitis, and then we had long discussions with the authorities in which we discussed, "Hmm, but, you know, necrotizing enterocolitis is hard to detect. It's often you make errors when you look at the X-rays." And we addressed and agreed with authorities to use this adjudication committee to assess our X-rays, and the belief was, at the time, that that would have been sufficient to exclude the non-NEC from the NEC, so to say, by scrutinizing these X-rays. Now, five years later, and I am not happy to tell you that that adjudication process did not adjudicate good enough, and therefore, we now have the results we have because it's so hard to define necrotizing enterocolitis. So the reason why we didn't power, why we didn't have mortality as a primary endpoint, was because we didn't know how to power it, and what we observe here in this study, 27% reduction, is far beyond, far beyond what we would have expected when we what we did expect when we started this trial. We were hoping to see a much smaller reduction in necrotizing, no, in death, when we started the trial. Because we couldn't dream of this result, so this is, this is, you know, this is beyond comprehension. Where does it... You know, what is this? This is the true effect of what you do when you have this very vulnerable population and you give them our agent. They survive. I think it's fair, Jonas, to say that if you want to do a study in the preterm infant on mortality, you have a huge challenge in terms of size and the possibility to actually get a positive readout, because that is the toughest endpoint you actually can select, according to my opinion. Yeah. But- Yeah, I agree. I agree 100%. Is it correct to say that the biggest work ahead is to understand and to tell the authorities why the mortality is decreasing with this drug, so to say? Is that the hard part now, to make FDA understand this, and- Yeah ... the European? I think like this. There is no requirement that you have to explain the physiology of your agent, but of course, we would like to understand more, and we will use all the available data and the knowledge we have. We have, for example, a lot of data on inflammation using this bug. We have TLR4 arguments that could come into play. We will look at this and, of course, plead our case in the best possible way. That's what we do as drug developers, and then it's up for someone else to assess what that is worth.... But in this case, we should remember this is not telling stories. This is not about that. It's about saving the babies, and the data alone, and please, doctors, and especially if you work in this field, that's the objective of the whole intensive care unit. You know, the whole thing that you do there in the intensive care unit, save the babies. Yeah, I really think that's a very good aim here. But also as a shareholder, I'm wondering, the market potential, memos, et cetera, and, analytics you have done has been based on the two primary endpoints as I can see at least. Maybe I missed out something, but is the market potential if this would be, if you would get approval on, with the secondary endpoint, is the market potential as big, you think, or, would it be- So I think that's a very good question, and it doesn't matter what I think. What I want to do is to provide you with figures that are based from the market itself. And we would like to go out and assess the value of what we have observed before we answer that question. So I think it's great if you could save people's life. I think doctors wants to use this medication. I'm convinced about that, but the market potential, we have to wait with for tomorrow. Okay. Thanks a lot for the answers. Let's move on. Staffan, maybe we could add, you briefly touched upon it, that the effect on mortality if we then do the exercise of looking at sort of organ systems that actually are the primary cause of death. Right. To start with, we do not see a difference in early deaths, so, you need probably a certain number of doses to get the effect. I think that's reasonable. I think it supports the idea of a causal relationship to the treatment and the. So if you group the registered primary cause of death, we work on GI and respiratory. We do not work on the brain, for instance, not the heart. So, that I think adds to the plausibility of this is actually related to the drug. Now, this is preliminary data. It's only a few observations, but nevertheless, it gave us support in believing that this is a real phenomenon we are observing here. Yes. Thank you, Jonas. It's clear that we have seen much more data than the people on the call, and we need to respect that. We're gonna give you more data as soon as we can. Let's move on. We have... Christopher is back. Christopher, you have another question, please? Yeah, thanks. I appreciate you taking my follow-up. So, in terms of the Kaplan-Meier curves for mortality and I guess, NEC while we're at it, I heard the Jonas's latest comment that it takes a while for it to separate, but, do you see... I mean, let's say after that first few doses, do you see any crossing of the curves, for either of those, endpoints? Thanks. No, no, we don't. We have looked at these things. We haven't shown them to you. We see no crossings. We see no effect in the beginning, and then it separates, and we see the effect that we observed at the 27% risk reduction of mortality. It's a very clear picture, and I would like to show it to you at one point, now or later, but we're gonna do it later. But it's very. There is no crossing, Christopher. This is consistent through all the data we have looked at, time points, subgroups, you name it. Okay, thanks a lot. We enjoyed them. I think that's fair. Yes. I just, you know, in terms of the next steps also, how long, you know, how much time does it take to kind of, you know, before you're ready to meet regulators, for example? That's a very good question, and we are not gonna wait long on that. We have a lot of communication to do, and we had, for example, a board meeting yesterday to align IBT, and we are also working on these things to communicate with the regulators. We're not gonna sit around and wait, let me tell you that. Thanks so much. No more from me. Yeah. Okay, let's move on with Georgie, please. Yes. Hi. I hope you can hear me. Absolutely. Hello? Hello, we hear you. So, yeah, thank you. I hear you as well. So, thank you very much, first, for the, very interesting and useful information. I have a practical question, in respect, to the possibility of registering a drug. It was mentioned before that, based, you know, on the experience with, the regulators, they are not obliged to look at both endpoints or just general data, and we are in a case where we don't meet endpoint one, but, basically, we rely on the mortality phenomenon for possibility of registering a drug. So my question is very simple. For the participants that are very experienced in this area, in matter of regulation, is there practice, known practice or similar examples of similar cases that have been successfully registered as drugs? Thank you for the question. I think it's a very good question, and you can look into, for example, people have done that. What has FDA in America done from 2018 until now? And there's data saying that one-tenth of all the products that have been registered have had a missed primary endpoint, and that has been registered on secondary endpoints or other available data. So I think if you have a drug that is needed, and you have solid safety and some solid data on the most important endpoint, I think, but it's me, that we should be able to register the drug with that data. And there is precedent that that has been done before, of course not with 9414. Okay, so we're not making like, you know, first path for this case? No, we're not Armstrong putting our foot on the moon for the first time. We're not that. So we're not that far off the standard track, but we have left the primary endpoint track. Okay. And then, my second question, which is the last I have actually, which is related to this question, is obviously it will take a time, it will be a procedure for talking to specialists back in there, further investigation of different matters in Central. But, I suppose there is some stage of this process where you could be, let's say, more certain that it's only a matter of details, but actually, drug approval is going to be achievable purely from, you know, like, medical data standpoint of view. Is my assumption correct? And if it is correct, according to your best estimate, when do you think you can basically reliably decide that you have a winning case at the end of the day? I think like this, we would like to discuss. We talked about indications, we talk about other things. We need to gather a few thoughts here, and then we're gonna go out and make sure, and this is always in the interest of IBT, to ensure that we are aligned with the regulators before we attempt something. We have not changed the protocols through any of our studies. We have not changed the desire to deliver on any end points. We are, in a way, very conservative there because we want to hear from the regulators that they are on board with what we do. Once we have that, I think the production and the rest of this stuff might be on a time-critical path for reaching and the market. But it's too early for me to actually comment on that in a fully transparent, yes, but with some actual information. Okay. Thank you. Thank you. Thank you. Next is Panigrahi again. Please, Doctor. Oh, you did mention that the number of days in the hospital was not changed. Did you measure gastric residuals? Was that being measured, or because that would have been another clear, quick indication. Okay. No, is the answer. But thank you for the question. Yeah. Erik Samuelsson is next on our list. Please, Erik. Hi, guys. Do you hear me? Yes. Could you comment on the likelihood of retaining the voucher, given that the primary endpoint on NEC is not? I think this comes to- Met? Yeah, I think this comes together with everything else, the Orphan Drug Designation, the primary endpoints, and the Priority Review Voucher, or the rare pediatric disease status, as it's called at this stage, is all linked to NEC. And remember here that we see a trend on NEC, but we didn't meet the primary endpoint. And we need to discuss further whether or not we should file for additional. We have to do additional paperwork for what we have seen, or if we still can use some of the documentation in place, meaning that it's still valid. So my comment to you, Erik, is it's too early to see where this goes. But your challenge is right. If we do not get the necrotizing enterocolitis endpoint into our label, then I think the voucher is out. But we're gonna file for a new rare pediatric disease status if we have to. Okay, thank you. Could I have one more? Sure. I guess there's a lot of laymen in this call, including me, and I've heard Jonas and yourself elaborate on a lot of stuff around the mortality, and if you could just make it easier for us to comprehend how you ensure that the observed effect on mortality isn't due to chance. Okay, let me try that. Jonas, you can correct me if I'm wrong. So what we do is that we collect the deaths. That's very robust endpoint. I mean, there is no diagnosis, there are no machines involved in that. We simply see when the babies, unfortunately, will pass. And they are divided into active group and placebo group. And then you do these tests. So you see, you run the statistics and see if. This is the number one we talked about. If your confidence interval for that observation is such that you do not, with 95% certainty, if you separate the effect of your active versus placebo. So that's a statistical test, okay? What we have then observed here is that the effect size, the point estimate, is 27%, and that the boundaries of the 95% confidence interval rests with a positive effect towards the active arm, in our case, IBP-9414. So that's how it's done. I don't know if that answers the question, but we are counting the number of deaths is the basis of this analysis. And maybe adding to that, then, are the consistent reduction in the risk of dying in different subgroups? I mean, you could have a very good effect somewhere, which could be dramatic, but in a small group of the subgroup of the infants, and we see this consistently across the subgroups we are looking at. Yes. That's one thing. The other thing is, when does the placebo and active arm, in terms of infants dying over time, separate? I think there was a previous question on this. You look at the number of deaths or survivors, if you wish, and they might be parallel, and then they start differentiating, and you look at what's given as the risk of death. If that, that risk, diagnosis coincides over time when you die, let's say you die from intraventricular hemorrhages early on, we don't see an effect there. But when you're treated for some time, the curves start to separate. That's an additional indirect, say, or for the causal relationship between treatment and death. Otherwise, it's very difficult to actually say, you know, with 100% certainty. We are talking about probabilities here. Yes. And that's why all the questions on the subgroups and things like this, if they are consistent or not, and, and that's what we're saying at this point, is that everything points in the right direction if you want to save babies. I think that's the conclusion. Okay, if, do we have any other questions today? I don't know. Have you seen anything in the chat? We have a friend here looking at the chat room. It's empty. We have used the phone. Thank you for that. We will now close this unless there are any final remarks, and I want to thank you for participating and your interest in IBT. As you can hear from Peter, Jonas, and myself, we are very committed to continue this journey. We would like to tomorrow to continue the work and to push forward and get this input from the regulators that we all, I think, together, are waiting for. And we will do that and come back to you and report what the outcome is as soon as we have something to report. Otherwise, feel free to contact us. We can, of course, set up a Google call like this again, if there is an interest. I think it was very nice and good to discuss in an open way- Yes ... what we are about to do. And also, thank you for the questions, to Peter's point. Very good questions. Good questions, and thank you for the contributors. With that, I think we say goodbye. Any final remark from anyone? Otherwise, we just say goodbye. Thank you. We say goodbye. Thank you. Thank you. Thank you. Good luck. Thank you. Good luck. Thank you. Bye-bye. I would say congratulations. Thank you. Thanks.