Good morning, everyone, and thank you for joining Alterity Therapeutics' shareholder webinar to review this morning's announcement of the phase II clinical trial results of ATH434 for the treatment of multiple system atrophy. On today's call, we have Alterity Therapeutics' CEO, Dr. David Stamler, who will be joined by Dr. Daniel Claassen, Professor of Neurology at Vanderbilt University Medical Center and the coordinating investigator of the ATH434-201 phase II study. Following the presentation, there will be a time for a Q&A session. If you would like to ask a question, please use the written Q&A facility at the bottom of your screen at any time during the webinar. The company will endeavor to answer as many questions as possible in the permitted time. Please note that your questions may be moderated or amalgamated to avoid repetition. If we run out of time or are unable to answer your question, please email our investor relations team. Also, a reminder that this webinar is being recorded and it will be soon made available on the company's website. I will now hand over to David to begin. Thanks, Anna, and welcome to everyone. Good evening in the U.S. and good morning in Australia. I'm delighted to be with you today to tell you about the results of our phase II trial in MSA. This is an excellent result, and I'm very encouraged for what this may bring to a much-needed and deserving MSA community. These are our forward-looking statements. I'm really happy to declare that I really believe we achieved all of our target measures for success. The drug ATH434 has demonstrated a favorable safety profile. I'll be sharing our strong clinical results with you and with a lot of focus on the Unified MSA Rating Scale. We have demonstrated evidence of target engagement on our biomarkers. The positive results stem from multiple areas that we studied. The clinical results were exceptionally strong, and that really means we did see robust efficacy on the Unified MSA Rating Scale, which is a measure of disease or functional disability with MSA. We've also seen evidence of clinical benefit on several secondary endpoints that are also important to MSA patients. We have observed reduced or stable brain iron concentrations, which is how we believe the drug is actually working, and we have early indications that 434 can be preserving brain volume when compared to placebo, and that's important because, as the name implies, Multiple System Atrophy means areas of the brain with this disease do shrink, so we're really trying to preserve that. Now, for those of you who are new to our story, I thought I would still review a little bit about the disease that we are studying to put the results in perspective, so MSA is rare. It is a rapidly progressive disease, and it is highly debilitating. Now, we refer to it as a Parkinsonian disorder, and that's because these patients have symptoms of Parkinson's disease. That's the motor symptoms that we've all seen before. It is an orphan disease. Now, it's estimated that up to 50,000 patients in the United States are affected with MSA. Disease characteristics can be quite heterogeneous, but they include motor symptoms that I talked about, Parkinsonism, but you can also have uncoordinated movements that lead to balance problems and frequent falls. Autonomic dysfunction or autonomic impairment is an important component to the disease because these patients have difficulty maintaining blood pressure, which can make it difficult for them to stand or walk. Sometimes even a large meal will cause the blood pressure to fall. They also have bowel and bladder problems and often require intermittent catheterization or an indwelling catheter. As depicted in the diagram on the right, patients may ultimately require a wheelchair. More than half of patients do require a wheelchair within five years of symptoms first appearing, and the median survival is only seven to eight years after symptom onset, so this really is an aggressive disease, and we are really aiming to try and slow down the progression. Our drug candidate is called ATH434, which we believe is potentially disease-modifying, and I think the data from this study and how we know the drug acts suggest that it really is modifying the course of the disease. The drug is a small molecule, as pictured on the right, binding iron, and it targets a pathologic protein called alpha-synuclein that is important when it's in its normal state for normal neuronal function. But in disease, it doesn't work, and that leads to neuronal misfiring. Now, the drug itself is an iron chaperone, which means it binds iron with moderate affinity and then can help redistribute it within the body for appropriate use. Now, importantly, because the drug is a small molecule, it can be administered orally and absorbed through the GI tract, and that is quite important because many therapies that are in development for MSA are injections or infusions, and often those injections need to be given once a month in the clinic. Doctors don't like that. Patients don't like that, so we're very happy that we have an oral medication, which is going to be very easy for patients to use. We have potential to treat other iron-related neurodegenerative diseases, and as referenced above, this is an orphan disease, and we do have orphan drug designation in the United States as well as in the European Union for the treatment of MSA. The trial design that we're disclosing today is summarized here. The design is a randomized double-blind and placebo-controlled design, and that really is the gold standard for evaluating the potential efficacy and safety of a drug candidate. In addition to those things, we also evaluated pharmacokinetics of ATH434, but we will not be reporting on that today. The population is an early-stage MSA population. We did enroll a total of 77 patients, and they received treatment for up to 12 months. The clinical endpoints are summarized there. The activities of daily living scale, that's the Unified MSA Rating Scale Part One, is the key clinical endpoint, and I'll go into that in some more detail. We also looked at global measures of patient severity, the motor examination, and various measures of autonomic function. We did look at brain biomarkers, iron and brain volume, and I'll touch on that in a bit. Fluid markers we looked at included neurofilament light chain as well as aggregated alpha-synuclein, but we only assessed that at baseline. And then finally, we did employ wearable movement sensors to look at patient activity in the outpatient setting. So this is a snapshot of what the trial looks like. Patients with early MSA would be randomized to one of these treatment arms in equal amounts and receive treatment for 12 months. And I indicated the key clinical endpoint before is this modified, I'm sorry, is part one rating scale. So this scale that you see, and I'm sorry, it just stands for Unified MSA Rating Scale if that wasn't clear. This is a validated rating scale that was developed specifically for evaluating MSA. There are four parts, but the part one and the one we're interested in assesses functional impairments in areas that are affected in MSA. Now, the modified version that we and many other sponsors use exclude the item of sexual function. Now, you see these items on the right side of the slide, and these are obviously items that are very important for quality of life. To be able to speak clearly, swallow without choking, handwriting, dressing, taking care of yourself, falling, etc. So that's why this is such an important scale. And to that end, it is the most important clinical endpoint that will be used to support a regulatory approval. Now, I did mention in the bullet before the bottom that this is rated from 0 to 48, and higher scores are worse. What we really want to see is negative scores, or we want to see those scores lower compared to placebo. The key eligibility for patients enrolling in the trial is that they needed to have clinical evidence of Parkinsonism. They needed to have evidence of autonomic impairment in various different ways, whether it's blood pressure, bladder function, or other motor impairment. The patients were required to be ambulatory without assistance, and they needed to have documented elevation of iron on brain MRI. Patients were excluded if they had motor symptoms for more than four years because we felt that those patients were too advanced to benefit from drug treatment. They were excluded if they had severe disease as indicated by swallowing and significant swallowing impairment or frequent falling as indicated by those frequencies on the slide. All right, so now let's turn to the results. These are the baseline characteristics, and they are a characteristic of early-stage MSA and what's been seen in other phase II clinical trials, so if you look at the column on the right, the average age was about 63 years, pretty typical. You can get people as young as in their mid to late 40s and into their early 70s. There was a slight predominance of males over females. The baseline score on the modified UMSARS was consistent with a moderate level of impairment, and we see some of the other parameters listed there, the motor scale, the NfL, and the duration of motor symptoms of just two and a half years. All right, so I'm now really happy to share what I think are truly outstanding clinical outcomes from this trial, so what you see on this graph here is the UMSARS part one score. On the y-axis is the score, and on the x-axis is time. What you see in the placebo, which is the dashed black line, is that there is just this steady march upward and an increase of about eight points over 12 months. That's very typical of other published data in similar patients. Now, what we saw was that the high dose statistically separated from placebo as early as six months at a p-value that was nominally significant at 0.05. At end treatment, we saw that the 50 mg dose group separated from placebo. Again, statistically significant at that p-value of 0.03. Now, put differently, because sometimes these changes in raw numbers can be difficult to interpret, that what that really means is that at the end of treatment, the low dose slowed disease progression by 48%, and the high dose slowed disease progression by about 30% with the p-values indicated there. Now, one of the questions that some of you may have is, well, why did the low dose perform better than the high dose at the end of treatment? And that's a question that we're obviously very interested in and we're continuing to explore. We don't have any definitive answers as yet, but what we do know is that the patients in the high dose group had clinical indicators indicating that they were either more rapidly progressive or they had symptoms suggesting or they had symptoms that indicated from published data that they were more likely to progress rapidly. We also know that we had some more dropouts in this dose group towards the end of therapy. So we're not really worried about this, and this is something that we will be exploring. We'll be doing very detailed pharmacokinetic analysis to try and understand this for any future trials and for future development. So I think the takeaway from these data is on this very important clinical endpoint. Both 434 dose levels demonstrated clinically meaningful slowing over 12 months when compared to placebo. Now, this wasn't the only clinical endpoint we looked at. We looked at a clinical global impression of severity, and that's to really allow a clinician who is looking at the whole patient, not just their motor symptoms or how they're reporting, but just the entire patient, their level of distress, to try and really understand how their disease is looking in totality. This is a seven-point scale where lower scores represent improvement. And what clinicians observed, kind of consistent with what we saw on that Unified MSA Rating Scale, was that there was a reduction of almost one point, minus 0.8 points with a significant p-value at the low dose. And again, the high dose clearly showed a trend that did not achieve statistical significance. Similarly, we looked at the Parkinson Plus motor score, and this is a scale that looks at all the different motor impairments that the patients may experience with MSA. And we saw trends in improvement in both dose groups at both 26 weeks as well as at 52 weeks. I mentioned the wearable movement sensors. These are sensors that patients wore for two weeks at baseline and then again at 13 weeks, 26 weeks, etc., and at the end of therapy. What we saw was that compared to placebo, we saw increased numbers of, or on average, there were greater step count in patients receiving active treatment. There were more bouts or episodes of walking, meaning patients were getting out of their chair and walking more. They spent more time walking just because we could monitor that and more time standing. This is obviously a rather objective measure that shows that we are benefiting patients from a motor standpoint. Finally, we did see improvement in orthostatic hypotension symptoms based on a patient-rated measure. We saw that on other scales on that component of the UMSARS. There was improvement on that as well. We're seeing improvement in multiple domains, which, given the fact that this disease does affect so many areas, is quite important. So now I want to talk a little bit about the positive impact on brain and brain volume. Assessing brain iron and brain volume were unique aspects of the trial, and we were fortunate to partner with Vanderbilt and Dr. Claassen, who will speak later, to try and implement some of these in this study. I consider these to be exploratory but important aspects of understanding how ATH434 works. Assessing brain iron with this modality has really not been implemented in clinical trials to look for a drug effect before we did it. We took this unconventional approach to really evaluate whether or not we could engage the target of iron and to really try and understand better how ATH434 works. Now, this led to our selection of the primary endpoint, which is change in iron content as measured by brain MRI. And this was assessed in particular regions of the brain that are known to be affected in MSA. And we did this because we originally felt this was the best opportunity to observe a drug effect. Now, this analysis, and by the way, I should say, since we began the trial and designed it, we've learned more about how ATH434 works, not only in patients, but also at a cellular level. And through the work of our Head of Research, Margaret Bradbury, with collaborators and experts in iron biology, we now have a different understanding of how ATH434 works. And to that effect, I think that is really helping us nicely put together the full picture. And as indicated there at the bottom, this analysis is quite technical, and we will continue to work with our partners at Vanderbilt to explore what all these MRI data are telling us. Now, brain volume is another important parameter, as mentioned. We want to preserve brain volume in MSA, and the parameters and the methods that were set up at Vanderbilt were quite important, and I'll be sharing some of those data with you in a moment, so focusing first on the brain iron, there's quite a bit on this table, so if you look first, these are what we see at 50 mg, and then on the right is at 75 mg, and these are the key brain regions that are affected in MSA, and what we see is at the low dose, at the 50 mg, either no observable difference or stable levels in brain iron or reductions, both at 26 and at 52 weeks, and in this one region called the putamen, that did achieve nominal statistical significance at 26 weeks. And in the pallidum, we saw approaching statistical significance at 52 weeks. Similarly, at 75, the pallidum, which is quite interesting, we do continue to see or observe reductions in this, but not in these other levels or not in these other regions. We don't fully understand this. I think we've learned that this is an interesting variable. You probably need hundreds of patients to better characterize brain iron changes with this method. But nonetheless, I think this was an important indicator that we are engaging with the target. So I would say that to summarize, we have shown target engagement, and we have demonstrated significant reductions in iron content in the putamen and in the pallidum, as indicated there on the slide. And we do see stable iron content in other affected brain regions. Now, this is brain volume that I mentioned previously. What we are aiming to do is to preserve brain. What you see on the slide is that both at 26 weeks in gray, this is the amount of atrophy in the placebo patients in gray, and then the low dose in blue and the high dose in green. What we see are trends in less atrophy or preservation of brain volume, both at 26 weeks and at 52 weeks. Now, this is the underlying part of the disease. It's quite important, but also challenging to prevent this from happening. What we're observing are initial signals that we are actually preserving brain volume. Now, I'm going to turn to safety. The safety population, which is a bit different from the efficacy population that I showed you before, this involves participants who received at least one dose of study drug. In the results, the safety results showed that ATH434 was well tolerated with similar rates of adverse events in both active treatment groups and placebo. Most of the adverse events in all dose groups were mild to moderate in severity. There were no serious adverse events that were related to ATH434. And discontinuations for adverse events were similar in the placebo group and in the 75 mg group. However, we saw no discontinuations for adverse events at 50 mg. Importantly, none of the adverse events leading to discontinuation were related to treatment. And this is not unexpected to see discontinuations in a trial with a patient population that is this sick. So in summary, we had an exceptionally strong clinical result as manifest by robust efficacy on the Unified MSA Rating Scale that was supported by evidence of clinical benefit on several secondary endpoints that are important to MSA patients. We also saw reduced or stable brain iron concentrations on MRI, and we saw trends towards maintaining brain volume when compared to placebo. So I am now going to pause for a moment and turn it over to Dr. Claassen, who is the coordinating investigator on the trial, to ask for his perspective on the data that we have generated and analyzed so far. Dr. Claassen. Thanks, David, and I appreciate the collaboration with Alterity and really on behalf of the MSA population that I and my colleagues treat. I just want to thank you for investing in this terrible disease. From my perspective, I really find these results incredibly compelling. To change the UMSARS trajectory is a huge win for patients. And so as a treating physician, we have been very frustrated in that there are no disease-modifying therapies available for MSA. And when I look at that graph, it makes me very excited that that story may be changing and we may actually have something to offer these patients. You can imagine as a clinician, you have a patient that comes in with symptoms of MSA, and the earlier you treat them, the earlier you are likely to try and alter the disease course. I think that's what I'm seeing in this data is that there is a potential that we could intervene early and change the course of the disease over time. The things that really struck out to me in terms of the data was it wasn't just one or two things that are moving clinically on the UMSARS. We really see things that are important to patients that seem to be different, including speech, swallowing, bulbar symptoms, dexterity, things like that. And so when I see that, it really makes me think that we have a real potential to be changing the disease course, which obviously affects the entire brain, so very encouraged by this data. Really looking forward to seeing how we can move quickly to try and see how we can get this therapy for patients. So as a clinician, I was very encouraged. Great. Thank you. Thank you, Dr. Claassen. Anna, I think that is the regularly scheduled portion of the program. I think we now probably want to entertain some questions. Yes, thank you. Thanks, David. Thanks, Dr. Claassen. We'll now move on to the Q&A section of this webinar. And just as a reminder to everyone, you are able to ask questions if you press on the Q&A button at the bottom of your screens. We have some questions that we've received earlier, so we'll start with those, and then we'll move on to the ones that have been asked live. So the first one is, how do these results compare to what you were expecting to see from patients, and have they exceeded your expectation? Yeah, so I'll start. I mean, we were confident that we could have some changes on biomarkers, and we thought we could observe some clinical benefit. I don't think we had a sense for the magnitude of efficacy that we observed. I think it's a striking result and one that is quite important because I think what it really tells us is that our strategy of targeting this labile iron to really interrupt the cycle of neurodegeneration and progressive neuron loss is feasible. So it's a dramatic result. I think Dr. Claassen's clinical commentary probably speaks volumes. I think I think small changes on this scale are important. So a big change of approaching 50% is big. It's big. I think it really means, and as indicated in that Clinical Global Impression of Severity, clinicians can see it, and patients can likely feel it as well. I think it's quite a striking result. Great. Speaking about patients, how do you expect this treatment to help patients? Maybe I'll let Dr. Claassen take that one. I think he touched on it, but perhaps he could talk about what MSA patients really experience and how ameliorating some of those may make a difference. Yeah, I mean, I think when you look at a patient that comes in your clinic with MSA, typically they have a lot of symptoms related to mobility, speech, swallowing, communication, blood pressure dysfunction that can make them very disabled. And so you try anything you can to try and keep them mobile or keep them active. So for instance, you might give medications to increase their blood pressure, or you might try things like levodopa therapy that we could eventually give to Parkinson's patients to improve their motor symptoms. And so up till now, everything's been symptomatic. But of course, patients want to come to you and say, "What can you give me that can change the course of this dreadful disease?" And I think many patients, when they get online, they look about MSA and they read about it, they're struck with the ominous future that they read about in terms of how rapidly the disease progresses. So as a clinician, I really want something that I can give my patients that I know can have a meaningful change to the slope or the direction of that decline. And so for me, this result really gives me optimism that we're much closer to that than we were before the result of this. And I think this is really the first time, in my perspective as an MSA physician, that I've seen such a dramatic change in the UMSARS trajectory. So I'm filled with optimism for my patients, and I think our patients are also filled with optimism that there might be something for them. And so I think that really gives me a lot of encouragement. Thank you. So in terms of these results, do they give you confidence for the potential use of the drug in other diseases such as Parkinson's? I'll jump in there and talk about that. I think we didn't discuss this in this presentation, but we know that the pathology that we're targeting in MSA is similar to many other neurologic diseases, and Parkinson's is notable because these individuals on brain MRI have elevated iron as well as abnormal or misfolding alpha-synuclein in the areas of pathology. It's very encouraging, and it's an area that we very much would like to explore of targeting other diseases where iron plays a central role. Obviously, Parkinson's disease as the second most common neurodegenerative disorder is an obvious one, but as many may know, there are investigators that are interested in targeting iron for Alzheimer's disease, and you need the right tool. You need to really target that labile iron that's involved in the pathogenesis of these diseases, so yeah, I think there are many options to consider. Thank you. And I think one of the biggest questions that we're receiving is, what are the next steps on the ATH434 program? Have you begun discussions with the FDA? Yeah. So we will want to accelerate and get those discussions with the FDA as soon as possible. That's going to take a bit of work. We firstly have to complete our analysis. We literally just saw these data for the first time late last week and have been working pretty much nonstop since we received them. So in addition to continuing the analysis, we need to write that summary and really engage with the FDA so that we can plan the next steps. So that's maybe the first order of business is finishing the work and engaging and requesting a meeting. Those things take time. The FDA is busy, but these are important data, and we will make that our top priority. We will also be presenting these data at major medical conferences where I think the reaction is expected to be quite positive. Dr. Claassen and I had an advisory meeting with key MSA leaders both in the U.S. and in Europe today. I think they shared the same perspective of Dr. Claassen that this is a remarkable finding. So I think continuing to roll this out and stimulate the interest in this strategy will be important. And then finally, we have had partnership discussions all along for several years, and they've been ramping up significantly in the last six months knowing that we've been closing in on data. So I will be thrilled to continue those discussions because I think they will be fruitful and hopefully will identify a good partner that, if it makes sense and is good for shareholders, will really try to bring somebody else into the mix for evaluating this drug. Great. Just a couple of questions on the data. What did you see in the SF-36 scores? We have not analyzed the SF-36 data in full. That's something that we will be disclosing at a future meeting. And I would say just keeping in mind, the SF-36 is a quality of life measure. So if you look at the hierarchy of clinical measures, the first thing you want to do is affect whether it's either a biomarker or a very subtle clinical sign. Then a functional measure is the next highest order of difficulty. And then finally, a quality of life change is most difficult. So I'm not fully anticipating an effect on the quality of life, but it is something that we will look at and report in the future. Okay. By looking at the natural history data, can you extract the amount of preservation of brain or slowing of atrophy you would need to see at one year or two years to determine the disease trajectory in terms of an overall survival has changed? I see. Oof, that's tough. There's maybe a short answer and a long answer. I don't think we learned that from our natural history study. Dr. Claassen was centrally involved in that and may have other thoughts. I think a study that looks at survival at one year, at two years, whatever, is a very different design. So you might need to do a much longer study on a small basis and then expand that. But Dr. Claassen, any thoughts on that? Yeah. I mean, I would say that our MSA Atrophy Index that we have developed in partnership with some NIH studies, we feel really good about that tracking disease progression. We haven't done a Kaplan-Meier assessment or anything on death because we haven't got that data yet. But I think my take home on the disease atrophy issue is that we're seeing signals that are suggesting that the treatment is altering that known progression, and we've established that through our other natural history cohorts. So I would just point that that's a new way to look at atrophy, and we feel very confident that's a better way to look at disease progression to MSA. Great. What do you attribute the lack of dose response? So are the end values too small to make that conclusion? Or rather, is there some maximum effect that you can achieve in terms of how much iron can be redistributed and the maximum therapeutic effect? Yeah, those are excellent questions that unfortunately I don't have clear answers to. I can only speculate. I mean, there very well may be a limit to what you can achieve with a drug, and that's what we really tried to explore. I don't know that we've identified that maximal effect as yet. As I mentioned briefly in my presentation, we know that the 75 mg dose group by the clinician's assessment had more frequent or had a greater rate of rapidly progressing disease, and that was assessed by the clinician at baseline. That was higher in the 75 than the 50 mg dose group, so I believe, and time will tell as we continue to explore, that the difference between those doses is more about the dose group than it is about the drug. But that is speculation at that point, and we really need to do a lot of work before we can make that determination. Thank you. Could you put the results from today into context of the Lundbeck MSA drug results and how they compare? Yeah, I can try. That trial reported out a year ago, and when they first reported the results, they only disclosed that they saw trends in efficacy. Then at last year's movement disorder meeting, they presented some analyses that I didn't fully understand that represented that they had a certain amount of disease slowing or slowing of clinical progression. But they didn't present the data the way we did. They presented with what looked like a mathematical model. Now, they reported that they saw slowing of, I believe, 19% at their higher dose. But there were no p-values associated with that. So it's a little hard for me to do a direct comparison. I don't know, Dr. Claassen, do you have any thoughts on what you've seen with the Lundbeck data? Nothing much more to add. I think it was a Bayesian analysis, and I think the clinical change was estimated from that. But I think it was obviously a little bit, well, quite a lot smaller effect than what we're seeing here. So that's my interpretation. Okay. Also, by the way, I should add, the trial designs were not entirely clear. They are not entirely the same. They treated people for a minimum of 48 weeks, but some went out to 72 weeks. So I think it may be a little tricky to compare the two studies. But I think the one difference, and I don't recall seeing a lot of safety data, but we know that we've seen quite good safety. I feel very good about that as well. Great. Next question is, when can we expect results from the NfL observations? And can we give any comments on these at this time? Yeah. So we're still waiting. So we looked at change in plasma NfL as well as change in spinal fluid NfL. We don't have data on spinal fluid yet. There's some additional analyses that are ongoing to clarify those results. Right now, our first look at the plasma NfL is we did not see big changes in the placebo or in the active treated group, which is a bit different from what we observed in the BioMUSE data. So we really are going to need to see the results from CSF to make a better determination on that. Okay. Next question. Why would this 70 mg show efficacy at 26 weeks, but the second half of the treatment shows similar rates of progression to placebo? Yeah, so we think that may be due to dropouts, and patients, if they were sick, that their last observation would have been carried forward, so that's an analysis that we're going to do. We will look at and report in the future on the patients that actually completed the trial to see if we see any hints there, so we do think that it probably has to do with disease severity and the fact that the patients were likely declining more rapidly, both at baseline and in the second half of the trial. Okay. I think this one is probably for you, Dr. Claassen. Are there certain domains of UMSARS Part I that clinicians and or regulators may consider to be more important or meaningful than others? I mean, I think, first of all, the regulators view UMSARS I as important for determining drug efficacy. There's not really a domain that makes them more interested than others. I think how a patient functions and feels is what's important. I think the UMSARS I is the best we have in terms of the scales for addressing MSA. Yeah, I would agree with that. I think just to remind people, the UMSARS was developed to assess disability and functional performance in MSA. So the total scale is important, and every patient is probably going to be a little bit different. Some patients may have more swallowing problems or speech problems. Somebody else may have more problems with walking or falling or dexterity, so it's very hard. This disease is heterogeneous, and that's why that scale looks at so many different types of symptoms. Great. Next question. Given the drug effect shows a significant slowing and decline at 12 months, far stronger than at 6 months, is it possible that the trend will continue post-12 months? And are you able to follow up with this cohort to say if a further year will make longer effect? Yeah. Interesting question. It's certainly possible that you would see a persistent treatment effect if you continue treating people. Follow-up is difficult because once a trial ends, it ends, and sure, you can always go back and try and get additional data from subjects after they leave a trial, but you'd almost have to create a new trial and reconsent people and evaluate them, which would be difficult. The return would probably be small, and I hate to say it, but it's true. Many of these patients have deteriorated so much, they won't be able to come back into the clinic for evaluation, so the one thing I would add, if there are any patients or patient advocacy groups on the phone, is that we know that, especially for trial participants, that there's going to be a real need and a calling for this drug. So we're going to do what we can initially to try and get trial participants on drug when we can make it available. Thank you. Dr. Claassen, do you expect the diagnosis of MSA to go up if this is approved? Yeah, I do. And it's probably because a lot of physicians are nervous about giving a patient a diagnosis of MSA because it carries such a severe prognosis. I think that if we have a therapy approved that alters disease course, our goal is to find these patients earlier. And so I think that will increase awareness, education, treatment of MSA, and ultimately, we will find patients who need this drug quicker. And I think because of that, we'll have an increased diagnosis of MSA. Great. Yeah, as is always the case, new therapies give people hope. But I think what Dr. Claassen said is quite important, so. Agreed. Awesome. I think there's NfL, I believe. I think we I think we covered most of them. I think there's a couple of questions about accelerated approval and will the data that we've gathered be enough to submit an NDA without a phase III? Yeah. So that's always a matter for discussion with the FDA. I think the clinical consensus so far is that these data are exceptionally strong. There are various mechanisms for accelerating drug approval, whether it's through the so-called accelerated approval pathway where you can use biomarkers to support other clinical trials if they're accepted. That's the accelerated if those biomarkers are surrogate markers for disease progression. Here, we've got a different story. We don't need a biomarker. We've got the most important thing, which is a clinical signal. This is a rare disease. This is a rare disease with a huge unmet need. So the agency will very much want to engage with us and talk about how we can accelerate the development and ultimately the approval. That's their mandate. They've really changed in the last five to seven years, as we've seen with the Alzheimer's disease approval. It's something that we're very much interested in and look to seek how to accelerate this regulatory pathway as much as possible. Great. I think we received another one on the trial. When will you have drug PK data for both doses to correlate with the findings? I don't know. We've not actually had time. I mean, I honestly don't know at this point. I mean, it's going to take. It's not going to be days or weeks. It's going to be months. So at this point, I don't want to say something out of school. I know our whole team would throw things at me if I did. But I think, put it this way, they will be highly motivated. And when we have those results, we need them because we need to know what is the best dose to take into the next phase of development if it's needed, or we need to know the right dose if we're going to commercialize this drug quickly. So we'll get to it, and we will report it as soon as possible. But right now, I don't have a good answer for you. Another question came through about the doses. Will you try larger doses in the future? Yeah. Well, that depends on that analysis. If it clearly shows that and by the way, with only 20 patients per arm, that's a very small number of patients. They could have been heavier or have various attributes. So we don't know. But if it's clear that on this analysis that there's a dose response, given the excellent safety profile that we observed, I think it's something that could clearly be entertained and discussed with the agency. There's a question about brain water content, how that impacts brain volume measures. We saw this type of issue come up with a prior study on multiple sclerosis. Can fluctuation in brain water content impact volume measures? They can. What we see is a linear decrease in brain volume and placebo, and that is attenuated in therapy. We do not see any strong evidence of edema. It's always something to think about when you're interpreting brain volume. The other thing I would say is that we have other analytic tools that we are looking at, particularly with an imaging outcome called neuromelanin, which looks at the integrity of the substantia nigra. We've been looking at that. There's some early preliminary suggestions that the drug is preserving neuromelanin. I think the way I interpret it is it's not just one imaging outcome measure that we're kind of hanging our hat on, but we're actually seeing kind of a confluence of different imaging measures that are not all impacted by something like edema or water. Great. Thank you. A question here. I'm sure all patients that are in here are wondering. Is there an avenue for participants that took part in the trial to gain access to the drug on an ongoing basis? And are any patients continuing treatment post-trial? Right now, there are no patients on drug because the trial concluded in November. As I mentioned before, we are exploring ways of providing drug to trial participants. We'll do our best as the development path and a regulatory path unfolds to do our best to provide expanded access where feasible. Great. We got a question on the 202 trial, actually. When can we expect results from the 202 trial? Yeah. We're expecting to release data in the second quarter of this year, second calendar year quarter, so sometime between April and June, and right now, but I have to say, right now, this is our first order of business because this randomized double-blind placebo-controlled trial has such a rich data set that's going to take a lot of our focus, but we will disclose those data sometime during the period I referenced. Somebody just sent a not really a question, but just a request for you to talk through your previous three FDA approvals on your record and just saying congratulations on the data. Oh, thank you. So the first was a development program in Huntington's disease. And that was actually the first that was a drug that treats the motor symptoms of Huntington's disease called chorea, which causes a lot of disability. And that was a challenging development program because, believe it or not, the regulatory authorities at that time were not convinced that treating chorea, which are abnormal involuntary movements, was anything more than a cosmetic problem, which I can imagine as what a movement disorder neurologist would think of that. But nonetheless, we persevered and were able to get that one across the goal line. Then more recently, in 2015 to 2017, myself and our head of operations and head of research were at a San Diego-based company where we got a deuterated form of tetrabenazine developed and approved for treating the same type of symptoms for Huntington's disease, but also an important movement disorder called tardive dyskinesia. Every development program has its challenges, even though whether it's the same drug for two different programs, we had very different challenges. So much like this one, those prior development programs, they don't tell you how to do it the next time. They just prepare you that you have to pay attention to everything and expect the unexpected. Thank you. Last couple of questions. Do you think that ATH434 would be beneficial for late-stage MSA patients given that the trial was aimed at early-stage MSA patients? I don't know. It depends how you define late-stage. We've done preliminary looks at our data. You often have exploratory analyses where you look at earlier stage versus later stage, and even in this trial where we targeted early, we could look at the earlier part of those and the later part of the early, if that makes sense. We see greater clinical benefit in those with earlier stage disease within our trial, so it's possible someone could benefit, but I think there's going to be diminishing potential over time, and that's why I think to the earlier question, is this going to increase the diagnosis? I think so because everyone who potentially has this disease will likely want to get on it as soon as possible once the drug is approved. Just to close it off, do you see a potential that the drug could not only show slow progression but reverse the disease? Well, we didn't see that. And that's a judgment question. I think to actually see improvement, meaning better than baseline, is extremely challenging in any neurodegenerative disease, and especially one that's rapidly progressive. So candidly, I would not expect that, even though I would certainly hope for it from a patient perspective. Okay. Great. Thank you. We've now come to an end of our Q&A section of this webinar. I'll give it back to you, David, to close your closing remarks. Yeah. Well, I think we've said a lot. And I am really happy that, given the tremendous effort that we and our clinical investigators, the MSA participants, the Alterity staff who have worked tirelessly, I am so happy to be able to share this news with you. I think it's a result that we really couldn't have hoped for anything better. And I am super enthusiastic about doing what we can to get this in the hands of patients and treating clinicians as soon as possible. So thanks again. And we appreciate for those investors who may be on the call, we appreciate your continued support. Thank you. Thank you, David and Daniel, for your time this morning. This concludes today's shareholder webinar. The recording of this webinar will be available in the events section at the Alterity website. Have a good day. Goodbye. Bye-bye.