Hi, good morning, all. Welcome to Neuren's Investor Webinar to discuss phase 2 results for Angelman syndrome. My name is Gerry Zhao, Vice President of Corporate Development at Neuren. Joining me on the call today from Neuren are Jon Pilcher, CEO, and Liza Squires, Chief Medical Officer. Jon and Liza will make the presentation today, then all of us will be available for Q&A session following the presentation. You can use the Q&A button at the bottom to submit your questions. Before we start, I would like to remind everyone that we will be making forward-looking statements during today's call, which are subject to risks and uncertainties that may lead to different outcomes. I'll now turn the call over to Jon to start the presentation. Thanks very much, Gerry. Good morning, everyone. Thanks very much for joining us. I know it's a busy time in reporting season, so appreciate your time, and we'll try and keep moving along quickly. Thanks also to Monsoon and FB Rice, as always, for hosting today. So, you know, we're here today to talk about the Angelman results, which we're very excited about. But, of course, we've got the unusual situation that we've been in trading halt for two days since the ACADIA Q2 announcement. So this morning is the first time the stock's traded since that announcement. So, so I will make some comments about that. Obviously, it's had a material impact. And I really... You know, I'm not gonna go into it in a lot of detail because we put out our quarterly, which had detail in it, a few days ago. There's much more detail available in ACADIA's transcript and recording of their earnings call, if you wanna listen to that. And also, a number of our analysts have already put out updates based on the Q2, and with very little change, really, to our valuation. So you know, for us, the future is all about NNZ-2591, and I think the value opportunity for everyone is all about 2591. But I'm acutely aware that DAYBUE is very important. It basically underpins our financial independence and gives us the ability to make the right decisions on 2591. And obviously, you know, it's important from a share price point of view, so certainly don't wanna dismiss that. But I just wanna zoom out a little bit and look at the big picture. I mean, Q2 DAYBUE sales of $85 million, that's an annual run rate of $340 million. Well ahead of the first hurdle for our sales milestone payments of the $250 million first hurdle. So if you went back before launch, you won't find anyone predicting that sort of outcome. So, you know, it really is still an extremely impressive outcome. And people are often quoting SKYCLARYS, which is the drug that Reata had that was sold to Biogen, and, I mean, I've referred to that deal, as you know, in the past as well. Just wanna point out that the quarterly sales of DAYBUE in the US have been higher than SKYCLARYS every single quarter since launch, and they launched about the same time. It's very similar market size, similar price. So again, any notion that this is not a fantastic outcome is just completely wrong, in my opinion. ACADIA's revised guidance of $340 million-$370 million for the full year sales would give us income of AUD 132 million-AUD 138 million, with no cost other than tax. So again, it will be a fantastic outcome if that's what comes to pass. So, you know, in conclusion, we are, as I said in the announcement the other day, we're very optimistic about the future opportunity for DAYBUE. There are two-thirds of the patients in the US that have still not tried DAYBUE yet. There's big potential for growth in the US in the short term, and then in the longer term, we have, the rest of the world coming on stream. And remember, the royalty rate is significantly higher for those sales. And don't forget, we've already banked $100 million from, from the rest of the world. So we feel very good about it... And that's, that's all I'm gonna say now, because I really wanna get to the more exciting stuff today, which is, which is the Angelman syndrome results. And I'm going to hand over to Liza in a second to, to go through that with you. Then I will come back at the end and talk about what it means for 2591 more generally in the future. And then we'll take Q&A, and as I said, we'll try, we'll try and keep moving, as quickly as we can. So, Liza, please, I'll hand over to you to go through the results. Thanks. Thanks, Jon. Angelman syndrome is a severe neurodevelopmental disability that has a significant impact on both the individual and their family. It's important to remember that this Phase II trial was extremely demanding, as it was the first trial of NNZ-2591, not only in Angelman syndrome, but we started in the pediatric population. This meant that we had frequent study visits, either in the clinic or at home, weekly during the treatment period, and these visits involved blood draws, examinations, and other procedures. We are so grateful to the individuals who participated and their families, because this would be a trial that would be demanding for anybody to participate in. Additionally, we'd like to thank the clinical study sites and the advocacy groups. We appreciate everyone's commitment and contributions to this study. Next slide... One of the reasons to believe and to move forward in Angelman syndrome was the knockout mouse model, where NNZ-2591 normalized the phenotype, as demonstrated here. Next. The study highlights include the NNZ-2591 was safe and well-tolerated, with no serious adverse events or meaningful trends in laboratory values or other safety parameters. Clinician and caregiver global efficacy measures designed specifically for Angelman syndrome showed improvement from baseline that was significant and considered clinically meaningful. The Angelman Syndrome Clinical Global Impression of Improvement mean score was 3.0. A score of 3.0, or minimally improved, is considered clinically meaningful in the neurodevelopmental disabilities. The caregiver overall impression of change score was 3.2, and 8 out of 12 children showed improvement. We also looked at a sub-analysis of the younger children in this cohort. The cohort included children ages 3-17, and interestingly, when we evaluated the 3- to 12-year-olds separately, we showed improvement measured by both the CGI-I and the CIC. Improvements were seen in clinically meaningful aspects of Angelman syndrome, including communication, behavior, cognition, and motor abilities, and these results further strengthen our confidence in the potential of NNZ-2591 for multiple neurodevelopmental disorders independent of the underlying genetics. Next slide. We'll move into the phase 2 trial design. This phase 2 trial in Angelman syndrome was conducted exclusively in Australia at Austin Health, Sydney Children's Hospital, and Children's Hospital Queensland. The study was a 19-week study, which included 4 weeks of screening and 13 weeks of treatment, 6 of which were titration, up to 12 mg per kg per day, and the remaining 7 weeks were continued dosing. The primary endpoint was safety, tolerability, and PK, and secondary endpoints included a range of efficacy measurements specifically designed for Angelman syndrome, as well as measures used in other developmental conditions. The key global measures specifically designed for Angelman syndrome included the CGI-I, the CIC, and the CGI-S. We also looked at the Bayley Scale of Infant and Toddler Development as an exploratory measure, although this measure is designed generally to be studied over a longer period of time than the duration of this trial. Next. 17 children participated in the trial. There was one screen failure due to abnormal safety labs in the screening period. 16 children were enrolled and dosed. There were three discontinuations: one due to an inability to comply with study-related safety measures, one due to a protocol deviation, the individual was found to have had COVID during the screening period, and one due to treatment-emergent adverse event of COVID-19. Next. The mean age in the study was 10.1 years, and there were 10 subjects in the 3-12-year range, and six participants aged 13-17. There was a fairly good balance between males and females, and the genotype was fairly well-balanced between non-deletion and deletion genotypes. The completer average developmental quotient was 12, with the overall developmental scores four subjects rating over 20 and 12 subjects less than 20. The CGI-S at baseline was a mean of 4.8, which would be considered in the markedly impaired range. Next slide, please. Next, please. NNZ-2591 was safe and well-tolerated. Most of the treatment-emergent adverse events were mild to moderate and not drug-related. There were no serious treatment-emergent adverse events. There was one discontinuation due to COVID-19 and no meaningful trends in the laboratory values, ECGs, or other safety parameters. The table on the right shows treatment-emergent adverse events in two or more subjects. Many of these events are similar to what I would have seen in the pediatric clinic when I was a practicing physician. I will point out that four individuals had seizures. Seizures is a common symptom of Angelman syndrome, and none of these were considered related to study drug, and all of these individuals were on polytherapy for epilepsy. Somnolence occurred in three individuals, all were mild, and two were related to study drug. Constipation was seen in 3 individuals, all not related to study drug, and diarrhea in 2 individuals, not related to study drug. Next slide, please. We'll now move on to efficacy. Next slide. Best practices were followed for the Angelman-specific CGI-I and CIC measures. The scores are located on the left-hand side of the screen, and I would like to just point out again that a score of 3 minimally improved for the clinician, the caregiver score of 3 is just rated as improved, and that this score is considered clinically meaningful in neurodevelopmental disabilities. All raters completed training to calibrate scoring and the interpretation of the scores among raters. This was done at study startup, and again, a follow-up calibration was done during this study. The anchors are seen on the right-hand side of the screen. Clinicians and caregivers rate behavior, communication, gross motor, motor function, and motor function. Sleep is rated by the clinicians only, and caregivers rate seizures, cognitive abilities, self-care skills, and GI problems. Next slide, please. 11 out of the 13 children showed improvement in the clinician-rated CGI-I. The forest plot on the right-hand side of the screen shows that all domains, the mean scores of all domains moved in the direction of improvement, and that the highest degree of improvement was seen in gross motor function, behavior, and communication. Again, clinically meaningful aspects of Angelman syndrome. Next slide. The caregiver CIC showed improvement in 8 out of 12 children. On the right-hand side, the forest plot of the domains shows the domains of greatest improvement were cognitive ability, motor abilities, mutism, and the ability to communicate, and again, these are all clinically important aspects of Angelman syndrome. Next slide, please. As mentioned earlier, we did a sub-analysis of the younger age group, and in the younger age group, all participants improved in both the CGI-I and the CIC. Next slide, please. Four subjects improved on the overall score of the CGI severity. Now, it is much more difficult to move the severity scale than the improvement scale, but again, we think it's important that four patients were able to move a whole category. This, the largest area of improvement was in the behavior domain. Next slide, please. We also looked at the Bayley scores. These are raw scores shown here, and improvement was seen in the majority of patients for the domains studied, and this is encouraging perhaps for future studies of a longer duration. Next slide, please. These are quotes from the clinician and caregiver notes taken from the CGI-I and the CIC, and they demonstrate, again, a theme of improvement in meaningful aspects of Angelman syndrome, including attention and focus, communication, motor skills, and behavior. Next slide, please. I'll now hand over to Jon to complete the presentation. Great, thanks very much for all of that, Liza. So I'm gonna talk about sort of the Angelman syndrome market opportunity, but then, what does this result mean for us for 2591 more generally? So, Angelman syndrome has a pretty well-established environment, probably more so than Phelan-McDermid and Pitt-Hopkins, and I'll come talk about that more in a second. The prevalence is sort of in between the two, so it's less than Phelan-McDermid, higher than Pitt-Hopkins, the theoretical prevalence, and the number of known patients likewise. So currently on the registry, there are just under 1,000 in the U.S., which is less than Phelan-McDermid, but a little bit higher than Pitt-Hopkins. So look, you know, this represents a very attractive opportunity, but we have to look at it in the context of what else is going on in Angelman syndrome, which we'll do here. So we do have one of the leading programs here in Angelman syndrome, but it's not like Phelan-McDermid and Pitt-Hopkins, where you remember there really is very little competition, and we're at the head of the race. Here, there are two products that are ahead of us. They're both RNA therapies, and in this public domain, so I can name them. I mean, Ultragenyx have announced that they've had an end of phase 2 meeting with FDA, agreed a primary endpoint and a trial design, and are intending to start a phase 3 trial by the end of this year. The second RNA company is Ionis, who recently published an intention to start a trial in the first half of next year, pending a meeting with the FDA. So if they get clearance from the FDA, as Ultragenyx did, then it's quite possible that there could be two Phase 3 trials running next year. Now, you know, there are certain aspects of what we're doing that give us an advantage and a big one is that we are an oral liquid medication, so, you know, extremely patient-friendly. Those other two products are administered by spinal injection, and it's not a single injection, it's a series of injections. And the Phase 3 trial that's been announced is gonna be a sham-controlled trial. So, so we have a big advantage in that respect. The other advantage we have is that, you know, and I as Liza went through earlier, we've taken all genotypes into our trial. So all, Angelman has a variety of different things going on in the gene: deletions, mutations. Because we're treating independent of the genetics, we're able to take all comers into our trials, whereas the other, those RNA therapies have not. So two advantages, but, you know, right now, today, it's not clear to us, are those advantages enough to think that you can go and run a phase 3 trial alongside those other companies at the same time in a small population? So it's something we need to do more work on, both with the community and obviously, we'll need to talk with FDA. There's some precedents now being set in terms of endpoints. We don't know if that's a precedent for the indication or whether it's, you know, purely drug-related. So compared to Phelan-McDermid and Pitt-Hopkins, we have a lot of work to do to work out what we're gonna do in the future here. But to be honest, when I was approaching this result, that wasn't the most important thing for me. The most important thing for me was: what does it mean about our drug and its applicability in neurodevelopmental disorders? And so that's what I wanna talk about now. So obviously, this is our third result. And, you know, we've put them here side by side, highlights from it, and strikingly similar. The safety profile has been excellent across all three and very similar across all three, which is in a good, very good position. The results in those key endpoints is very similar. I mean, you can see Phelan-McDermid was a little better than Pitt-Hopkins, which was a little better than Angelman, but really, they're very, they're very similar. And, you know, we moved patients from that CGI-S, which is not easy in a 13-week trial. It's not easy at all. We've moved them in all three trials. And then when you look at what improvements we've seen, not only are they important things in the disorders, but again, they're very similar across all three. So we think really this is great validation of what we'd always said, we think this should be a multi-indication platform. Also, you know, we got great results in the mouse models of all of these things before we did these trials. You can't always rely on mouse models. They don't always. They certainly don't replicate exactly, but they don't always replicate at all in human trials. But we've seen pretty good correlation here. So all of that is incredibly encouraging for us as we move forward. So, so we have three ticks now against those three indications. We've got a really important meeting coming up in September with FDA, an end-of-phase 2 meeting on Phelan-McDermid syndrome, where we'll present our plans for, for what we think we should have to do for, for registration, and we'll get their feedback. So it's a very important meeting. Of course, you also know we have a, we have an Open IND with the FDA for Prader-Willi syndrome. We paused that trial, but that's still an Open IND. And we're also advancing non-clinical studies across multiple undisclosed indications. Then we shouldn't lose sight of the fact that ACADIA has rights to Rett syndrome and Fragile X syndrome. If they choose to develop them, we get the same economics as we do for DAYBUE. It's not the main game for us, but it is, again, great upside, given this broad applicability across neurodevelopmental disorders. So I've said before, you know, our main priorities in the near term are getting Phelan-McDermid syndrome and Pitt-Hopkins syndrome, you know, as fast as possible towards the market. We're in the lead position there. We're not following anyone, we're setting the path, and we really have the opportunity to do what was done in Rett syndrome in those two indications. Angelman syndrome, I've said we've got some work to do. We've got more analysis to do for a start from the trial, but then we've got some work to do to work out the best future strategy there. And then we have all these other indications following on behind, which could hold a lot of value. So I think overall, we think we're in a great position, and you know, this trial really has cemented that, and we're delighted with the outcome. So that's the end of my prepared remarks. We'll now get to Q&A. So just bear with me a second while I get them up. Now, some of these I will have answered in my statements, but I'll read them anyway. So first one: "How do these results impact your potential licensing decisions for NNZ-2591?" Look, I don't think these results on their own make any difference, other than, as I said, greatly improving our confidence, and I think hopefully increasing the confidence of others. FDA meeting, very important. Until we know exactly what the phase 3 trial can look like, we and others are not gonna be able to make firm decisions around that. Second question: "Are these results in Angelman syndrome sufficient to move to a phase 3 trial?" So I think I've answered that already in my comments. As I said, you know, the one difference with Angelman syndrome compared to the other two is that there is some precedent already set. And sorry, there is one other difference which I should have mentioned, different division of FDA. So, Phelan-McDermid and Pitt-Hopkins are in neurology. Angelman and Prader-Willi are in psychiatry, so it's a different division of FDA. So I think the meeting with Phelan-McDermid syndrome, we think ought to be instructive for Pitt-Hopkins syndrome, but not necessarily for Angelman syndrome. Next question: How are you balancing the ethical imperative to get NNZ-2591 to those in need of it as quickly as possible, and the fact it's likely to make so much difference with the options for optimizing share price for shareholders? Yeah, I mean, of course, we do have to balance that. That's a tricky thing, but it's front of mind to us. I don't think they need to be mutually exclusive. And it's funny, I don't think the speed of getting to market doesn't always necessarily depend on who does it. It's not right that other people can necessarily do things a lot faster than we can, for example. So I don't think the time really necessarily depends on who does it. But anyway, I can't say any more than that, other than we're very aware of that, and we do obviously strive to balance that. Next question: Congrats on the outcome. This is another excellent validation of the drug and important further evidence of its replication of the mouse models. Does this result provide strength to the argument that positive future mouse model results will also likely result in positive human outcomes? The undisclosed additional indications come to mind. So look, I did mention the mouse models, obviously, in my remarks earlier. You can never be sure of these things, but of course, the more evidence you get of the type that we've got, you know, the greater your confidence becomes. Next question: Can you describe what these changes in scores mean in terms of clinical parameters, behaviors, or symptoms? Otherwise, it is hard to understand what the improvements were from a practical level and how meaningful they were. Thank you, and that's actually from a parent of an Angelman syndrome child. So look, it's interesting. I'm gonna draw a parallel with Rett here because, ACADIA, you know, we said this the other day, ACADIA has just put out real-world data, which is a lot of, you know, specific stuff about what's being seen in use, and that's actually much more understandable than scores on clinical trial endpoints, which unfortunately is what you have to do from a regulatory point of view. So I can understand that there is that difficulty, and I think it's really useful now for ACADIA to have that real-world evidence. Look, all I can do probably is point you to the slide that we've got in the presentation of the testimonials from both clinicians and caregivers, which give practical examples from the kids of what sort of things they saw in this, in the trial. I mean, we certainly heard that. We weren't, unfortunately, we didn't have the safety data at that time. We do now to offer open-label extension, continued use of the drug, and we certainly understand that people were wanting that, which unfortunately we couldn't provide this time. Next question: Do you have any feeling as to how these data would translate to older Angelman? So I guess if you probably mean older than the trial population, which went up to 17. So look, I don't think we have. We don't have any data, obviously, so we can't make any strong statements about that. I mean, all I'll say is, again, that as with Rett, mechanism of action is not age dependent. You know, it's not something that shouldn't work in older individuals, and that's exactly what's happened with Rett, with trofinetide, which is the same theory, that, that it's able to be and is being very successfully used in older people. So we hope so, but we certainly don't have any data to support that at the moment. It was mentioned that the patients are continuing with the drug. No, so that's not right. They're not. I think I just, I just covered that. We will obviously offer that in a, in the next trial. We weren't able to at the time we did, we did these trials, and that was the same in all three of them. Hi, Jon, great result for Angelman syndrome. Can you make any comment on the efficacy and safety of NNZ-2591 versus DAYBUE? So look, the DAYBUE has a great safety profile. It obviously has one tolerability issue, which is the diarrhea. It's very clear from all three of our trials that we don't see that with 2591. Next question: When will the additional indications be announced? Sorry, I'm not gonna tell you that. We'll do that at the point that we've got, you know, sufficient confidence to do that. Next question: Is Neuren's preference to run the phase 3 trials itself? So, you know, I've talked about this in many times before. There's no doubt that if you can do it, you'll create a huge amount of value compared to now, and I've given the examples of our ACADIA phase 2 deal versus our ACADIA post-phase 3 deal, just completely different economics. And that wasn't even global. That was, you know, just on rest of world. You've seen the example of something like the Reata deal of a drug that's about to hit the market. So that it, it's not just that the risk has been reduced and the investment's been made, it's that you've got a product, you know, ready to go from a sales point of view, which attracts way more companies, and they'll pay way more for it. So there's no doubt, everything will tell you there's a massive prize for us if we can do it.... We still need to get to the FDA meeting to know what it looks like and confirm what it's gonna cost, and then we'll make that decision subsequently. Next question: How do the results compare with the other two candidates for Angelman? I'll start this, and then, Liza, you can chime in if you'd like to. So look, it's very difficult to compare studies side by side. I mean, that they were all open label studies, which probably makes them more comparable. But, those two studies were long periods of treatment, you know, to a year or, I think between six months and longer than a year. So very different, and, and that's why they had some endpoints which are suited to that length of time of observation and not suited to 12 weeks of treatment. So there's not much direct data comparison you can make, but the things that you can look at with the snippets of CGI, for example, that the two, those two results have disclosed, we're very competitive with, with those candidates. Liza, anything else you wanna add to that? No, I don't have anything else to add. No. No. No. Okay, thanks. Next question: Has there been any unsolicited approaches for takeover of any kind? It won't surprise you to hear I can't answer that. I'm not going to. I'm sorry. Are you able to include data from multiple indications in your end of phase 2 meeting with FDA for Phelan-McDermid? So, you know, we said before, that meeting is purely on Phelan-McDermid, and you can't really sort of put top-line results to FDA, from other indications, so it will be purely on Phelan-McDermid syndrome. But we expect certainly that data will be extremely useful across all across each of these indications. It will be extremely useful subsequently having all of that data across the different indications. Next question: Do you have an understanding of the mechanism of action within the patient's body, and why did several patients not respond? So, very succinctly, you know, the mechanism of action is to improve the connections between the brain cells and the maintenance of the connections that are already there through the action of IGF-1 in the brain. And that's a similar thing that you're trying to achieve with trofinetide. So patients not responding, there are patients who don't, didn't—don't and didn't respond to trofinetide. There are patients who haven't responded to NNZ-2591 in this clinical trial. It's certainly not unusual. You never get trials where everyone responds. Don't know for sure why that's the case, but it's certainly not unusual, and we're very heartened by the fact that it's so few that haven't responded. Okay, how comparable are your latest results against the other phase 2 trials for the RNA drugs? I think I've just answered that one. Next question: Congrats on the result. Was wondering if you could give your perspective on how the improvements would compare with the natural history study. So I think the issue here is that the natural history study, again, is not designed to look at stuff over a 13-week period. You know, it's something that tracks change over a much longer period, and so I don't think it would be worthwhile comparing them directly. All I would say is, you know, in a three-month period, you would expect very little change in the natural history. Liza, are you happy with that? Anything else you wanna add? Mm-hmm. Nothing else. No. Okay, thanks. Next question: Is Neuren considering bringing a partner to funding as a NNZ-2591, should it proceed to phase 3 for the different trials? If not, what's the estimated cost of the phase 3 trials? So I think I've already answered the first part of that question. We have talked with potential partners and continue to do so. Estimated cost, I've said publicly a number of times that I think for each indication, I think between $50 million and $100 million is the right range per indication. We'll hone that down once we have some certainty on the trial design. And so, sorry, and I guess a postscript to all that. Again, I've always said publicly, I think with our financial position, that DAYBUE has given us, you know, we could comfortably fund two indications ourselves, probably not more, with the current financial resources. That's what I've said in the past, through phase 3. Next question: Congrats once again, all. Could you share more color on the similar domains that improved across the different phase 2 trials? I sort of did that in that chart. I mean, Liza, is there anything more we can say other than, you know, the headline? Yeah. What's included in the chart is really the key messages there. Mm-hmm. So communication, motor skills, behavior. Yeah. Next question: Are more mouse models for different diseases happening? So we've said various non-clinical studies are in progress at the moment in, other indications. Next question: Re: Bayley-4, the data looks pretty encouraging. Do you think with longer timeframe, these are likely to improve further? Any thoughts would be welcome. So, like, I think as Liza said in the presentation, it certainly does. The trends you can see in only 13 weeks, which is not the length of time you'd typically use Bayley overall, are, I think, very encouraging, and I think certainly, my personal expectation is that you should see more effects with a longer period of treatment. Liza, do you wanna go any further or disagree with me? No. Okay. Next question: Are there further mouse model studies being undertaken? I've just answered that. Did you see any difference in outcome in mutation versus deletion subtypes? Yeah, that's a good question. As I said, you know, one of our advantages, we can treat multiple different genetic types here, and no, we didn't see any difference in the outcome across those different types. Obviously, the numbers are very small, but we certainly didn't see any difference, which gives us confidence that we would continue to try to treat all types. Next question, one for Liza, so I'm not allowed to answer this one. Why do you think the improvement changes were more consistent in children? I think you probably mean the younger children. And has this sub-analysis been done for the other disease indications that NNZ-2591 was tested in? So, you know, the main probably hypothesis around why younger children may do better could be related to central nervous system plasticity, the idea that, you know, younger brains are more able to adapt and are more likely to improve over time. And with intervention, obviously, we know that NNZ-2591 does support synaptic plasticity due to the mechanism that Jon referred to earlier, and so I think that is part of it. I think also the, you know, I wanna point out that the PMS study was in 3- to 12-year-olds, and when we look across our indications, that was the indication that had, if you will, the best results when it comes to the CGI-I and the CGI-S. We have not taken a deep look at the PMS results. However, you know, it was certainly... I think we would see something perhaps similar, but not quite as robust as we happened to see in Angelman's. I think you mean Pitt-Hopkins, don't you? Excuse me, yes, Pitt-Hopkins. Yeah. Yeah, and I think that the numbers were not big enough probably in that either. Now, I just so I agree with everything Liza just said. I just wanna counter that with, again, referring back to DAYBUE, where, again, the mechanistic theory is very similar, but actually it's being used, you know, across all ages, and in the clinical trial, in the Phase 3 clinical trial, there wasn't a difference in results across the age ranges, and obviously, that was with bigger numbers. So I'm certainly not at the point where we think, oh, it's, this is only good for that younger age group, but it certainly does look that in this setting, we certainly got a stronger result. I mean, the other thing that I think, you know, whether this is a factor, but, teenagers with Angelman syndrome, you know, participating in this really challenging trial that Liza described, is probably more difficult than younger kids participating. Now, again, it's completely anecdotal. Whether, whether that's anything to do with it, we don't know, so... Next question, I think we've answered this. I'll read it anyway: But the younger patient cohort had stronger data, wherein we don't seem to have seen that with the other trials. Anything specific to Angelman which explains that? But I think we've answered that. Okay, next question: Can you elaborate on the Bayley-4 scores? How much of an improvement was recorded? Is it in the double digits? Oh, look, again, gotta be careful here. This is an exploratory endpoint that's not designed for a 13-week study, so we were really looking at trends rather than specific, you know, specific scores. I mean, you, you can see on the charts, you, you can work out the scores. I think the, the scale is there. There is some debate over what's clinically meaningful on the Bayley-4. It's not, some people say it hasn't been determined, some say it has. Some of those scores exceeded what is seen as clinically meaningful, some didn't, of the improved scores. But again, I think that's just getting into a little bit too much detail, given, given the trial. It's just a trend that we think is very encouraging for us, given the regulatory precedent that potentially has been set. Next question: When is the meeting with FDA to change the safety protocols for NNZ-2591, so future trials can be easier to run? So you don't have a general meeting with FDA to change a safety protocol for all your indications. That's not the way it works. You have meetings with FDA about an indication. So what we'd said was, we're presenting all the safety data to the FDA in the Phelan-McDermid syndrome and the phase 2 meeting, and if they're comfortable with that and with what we're proposing for the phase 3 trial, then we will be able to have different phase 2 protocols for the other indications. But for the other indications, you still have to go to FDA and propose those indications for the trial. So there's a sequential thing here, so it'll happen subsequent to the Phelan-McDermid syndrome meeting. Next question: Do you see any future capital raises coming to proceed further trials, even though we have royalty coming in every quarter from ACADIA? So I said, again, referred to my previous comments about I think we can comfortably fund two indications ourselves. We have two indications that are top priority, Phelan-McDermid and Pitt-Hopkins. So, the short answer is no, I don't foresee that happening. Next question: Has there been any further consideration of a share buyback to protect constant relentless shorting of stock price? Obviously, at such low prices, there would be great scope for a lower capital ratio, capital be desired to fund trials. So, you know, I'll repeat what I've said before, we are keeping a constant review on capital management, including potential buybacks. I think, you know, personally, I'm not sure we should be, you know, buying back and then raising, and then buying back and then raising. You know, that's not what we should be doing, and you can't continuously buy back. So, you know, we certainly need the market to settle down, given big pieces of news that are out, before we would think about that. But just, you know, rest assured, we're keeping it under review the whole time, and we'll do it if we think it's the right thing to do. Next question: Will the patients be followed longer? When will you present longer follow-up data? So I think, as I said, we weren't able to offer extended treatment in these trials. We certainly will in our subsequent trials. Next question: Would you agree that if a phase 3 trial goes ahead, it will be another four years until FDA approval might eventuate? So look, I'm not gonna put out any timelines yet because we haven't got the design of the trial or anything. So all I've said, again, publicly, is the best thing you can look at is a third-party benchmark, if you like, which is the ACADIA Rett syndrome program. That took two years from start to finish for the phase 3 trial, and then you had the FDA approval process. So that, you know, that should be a reasonable benchmark, but certainly not gonna give any timelines yet until we have the plan going forward. Next question: What did you see in terms of the other exploratory non-specific efficacy measures in Angelman? So look, the outcome was similar to the Pitt-Hopkins trial, that we didn't see what we think were useful things in those measures, so we wouldn't be proposing to move forward with those other measures. Sorry, I'm laughing. The Angelman syndrome parent, who I know well, has just added a joke to the Q&A. I'm not gonna read it out, but it made me laugh. Right. That's all the questions that people have submitted, except I think there were some pre-submitted ones. Sorry, let me just try and find those. Just bear with me. There's only a few. We're nearly there. I think we've... One is about comparing the data with the, with the Ultragenyx and Ionis trial, so we don't need to cover that. Ongoing short selling impacts, how and when this is likely to be overcome? Again, I think I've said as much as I can on that. I hope I've covered this one, but, again, I'll read it anyway. Hi, Hi, hi, team. Congratulations. Now that we have our positive third results, seemingly we have a platform asset, which is exactly what I've said. Where do you see the direction of the company over the next 12 months? What's our roadmap? Finally, do we envisage discussions with Big Pharma? So again, I hope I've answered that. But again, to reiterate, two indications, top priority, move them as fast as we can, but we've got to talk with FDA first and, get their buy-in into what we want to do. Then we've got all of these other indications that we need to work out the best way to move those forward, including undisclosed ones that we'll talk about in due course. As for discussions with, and I'm not gonna specify Big Pharma, but other pharmaceutical companies, I've said before, we've had a number of discussions, and we'll continue to have discussions, but, we need to get through that meeting in September before we'll say anything, more concrete than that. So I think, that is it. So again, thank you very much, all of you, for participating. As I said, you know, right in the middle of reporting season. We're really excited now to move forward, two things with NNZ-2591. Just keep getting better, and, you know, we're incredibly enthusiastic about it and looking forward to the future. Thanks, all. See you next time.