Thank you for standing by. My name is Tina, and I will be your conference operator today. At this time, I would like to welcome everyone to the Atai Beckley BPL-003 Phase II-B Open-Label Extension Study Data conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. To ask a question, simply press star followed by the number one on your telephone keypad. To withdraw your question, press star one again. Thank you. It is now my pleasure to turn the call over to Ashleigh Barreto, Investor Relations at Atai Beckley. Please go ahead. Thank you, Operator, and good morning, everyone. Before we begin, I would like to remind everyone that this call will contain forward-looking statements, which are subject to risks and uncertainties. Any statements regarding future events, results, or expectations are forward-looking statements. Please note that these forward-looking statements reflect your opinions only as of the date of this call. We undertake no obligation to revise or update these forward-looking statements in light of new information or future events, except as required by law. Information concerning factors that could cause actual results to differ materially from those contained in or implied by such forward-looking statements are discussed in greater detail in our recently filed 10-K, available on our website or on sec.gov. I'd now like to turn the call over to the host, Dr. Srini Rao. Srini, over to you. Good morning, everyone. I'd like to start by welcoming you to today's webcast, our very first as AtaiBeckley. I'm joined here with Dr. Kevin Craig, AtaiBeckley Chief Medical Officer, and Dr. Robert Conley, our newly appointed Chief R&D Officer. Over the course of the next few slides, we'll walk you through the results of the Open-Label Extension of the Phase II-B trial of BPL-003 in patients with TRD. Next slide, please. All right, this slide provides a summary of the results of the Open-Label Extension. In summary, a second dose of 12 mg administered eight weeks after the initial dose of 12 mg, 8 or 0.3 mg, in the core study resulted in rapid, clinically meaningful additional antidepressant effects. These effects were sustained for up to eight weeks and resulted in a response rate of 63% and a remission rate of 48% in those subjects that received either 8 or 12 mg in the core study. The drug was well tolerated, with the majority of Treatment-E mergent Adverse Events occurring on the day of dosing. Most were classified as mild or moderate, and they were transient in nature. BPL-003 has the potential to fit into the established two-hour interventional psychiatry treatment paradigm, as we'll see in subsequent slides. Finally, just to remind everybody, BPL-003 was recently granted a Breakthrough Therapy Designation by the U.S. FDA for adults with Treatment-Resistant Depression. This is a recognition of its potential to deliver substantial improvement over existing therapies. Okay, I'll now hand it off to Kevin, who will provide an overview of the results of the core study. Kevin. Thank you, Srini. I'm going to now talk a little bit about the study overview and the focus on the core study. This is a review of what we discussed previously, really as a setup for the Open-Label discussion later on. Next slide. In terms of the study design, this was one of the largest, or the largest study of 5-MeO-DMT. It was a study that was conducted globally across six countries. We randomized 193 participants. Those that were eligible were washed out of their medications. This was a monotherapy trial. Then they were randomized to one of three doses, either 0.3 mg, which was a controlled arm. This was chosen in conjunction with the regulators to have, rather than a placebo, some chance of receiving a psychedelic drug on all three arms. And then the two active arms, the 8 mg and the 12 mg, these were chosen explicitly to be active and to be in the therapeutic range. So although we were expecting there to be a dose response, we very much wanted to look at two doses that were likely to be efficacious. Participants were assessed after dosing on day one. They were, t heir MADRS was assessed at day two, day eight, day 29, and day 57. So an eight-week blinded follow-up period. And the primary endpoint was the day 29, week four MADRS assessment. After completing that double-blind period, participants had the opportunity to roll over into the Open-Label Extension, where they received a single dose of 12 mg and were followed up for a subsequent eight weeks. Next slide. So the final results on efficacy are shown here. The first thing to point out is the control arm, which we see a fairly reasonable decrease from baseline in the control group. And I think this is very encouraging to us. This looks very similar to other psychedelic and TRD trials, where we see a decrease as expected. So I think we were encouraged that there was no placebo effect here, and this showed that this was a robust trial. Moving on to the active doses, what we saw was a rapid decrease from baseline to day two. It really reached its maximum around day eight and was very sustained thereafter to week eight. There was a small numerical difference between 8 and 12 at the day 29 endpoint, but I'd point out that this is really not a statistical difference. This is really just a numerical difference, with the eight seeming to be slightly better than the 12. But what is important is that this was really sustained all the way out and was statistically significant really from day two all the way to week eight. Next slide. Moving on to the responders and remitters, what we saw here on the left, the responder rates, this is patients who improved by at least 50% on their MADRS after dosing, is that we saw about a third of participants by day eight reaching responder status, and that was really sustained all the way out. And there was no difference really between the 8 and the 12 from day eight all the way out to week eight. On the remission rates, we saw a numerical improvement here of the 8 relative to the 12, with about a quarter of participants meeting remission status, again, by day eight and remaining fairly sustained out to week eight. Next slide. Just moving on to a summary of the safety for the core study. What you can see here is, I think, a very well-tolerated study. We had more than 99% of treatment-emergent adverse events were either mild or moderate. We had no serious adverse events throughout the trial. But what you can see here is now a beginning of a separation in terms of the doses. So here we saw that 12 had adverse events, then eight. And for example, if you look at the anxiety rates in the eight, they were fairly low, higher in the 12. What we see otherwise is a pretty expected list of adverse events: nausea and vomiting, headache, anxiety. We also had administration site pain and discomfort that comes with the nasal delivery of the compound. We had an increase in blood pressure, as again, expected for the class. Blood pressure increases were transient. They really were returning to normal within about an hour. The majority of these adverse events occurred on the day of dosing. Finally, really important for our product profile was the time to discharge. We looked at that with a specific measure. The majority of patients were deemed ready for discharge at the 90-minute post-dose assessment, which I think fits into our idea of making sure that these patients can be dosed and be ready for discharge within a roughly two-hour time period. I think looking at the safety profile, unlike the efficacy, we really do see the benefits of the eight mg here in terms of safety with very similar efficacy, and it was for that reason that we are proceeding with the 8 mg dose in future trials. Next slide, so finally, then just to talk a little bit about the study design or the setup for the Open-Label phase. As I mentioned, those that completed the core study were eligible to move into the Open-Label phase. Not all sites had the Open-Label phase available at the beginning of the study. Once they were available, about 126 participants were completed and ready to move into the Open-Label, and of those, 107 were dosed with a second dose, and they were followed up again for another eight weeks. The intent here was primarily to look at safety after a second dose, but also to look at the effects in terms of efficacy on a second dose, and with that, I'm going to hand over to Rob. Thanks very much, Kevin. Now I'd like to go over our top-line findings from our Open-Label Extension study. Next slide, please. This study, which, as Kevin had mentioned, was really a subset of our core study, has a very similar demographic profile. Again, of course, same population, more or less, somewhat female-oriented, very chronically ill, with moderate to severe depression going into the overall study. Next slide. What you see here is the change over time in our group means. The top gray line, you can see the group that got pseudo-placebo, the low dose in the first study. You see that curve on the left. And then you see they improved quite a bit when they got what was, to them, the first dose of active medication in that second Open-Label study. You can see the shape of the line was very similar to what we saw in the first administration of the active drug arms, which is somewhat reassuring of our effect size and change over time. In the two active drug arms, however, we did see even more improvement after we gave the second dose. You see an improvement in the 12 mg arm, which is the dark line, and then in the light green line, which is the eight mg arm, quite a robust improvement over time. And importantly, with the one dose being given at the beginning of the Open-Label study, you see this in continued improvement out to two months. So we really do have 16 weeks of good follow-up with improvement in depression with just the two doses during that time. With all of this data in front of us, we have decided to move forward with recommending an eight mg dose for our phase III studies. The next slide. Now, this looks at our response in a somewhat different way. This looks at our responder rates. And again, response here is defined by at least a 50% loss of the initial MADRS score, the depression score. Left-hand side, again, you see our core data one more time. Now you see after the second dose on the right-hand side that you get this greater improvement with all of the cells going up, particularly the eight mg cell. You see we actually get to an 81% responder rate over time. This is the improvement of response, again, with just that one single second dose. So again, very encouraging for persistence as well as improving response over time. The next slide. Next slide looks at the remission rates. Again, remission is this very high definition of response where people have a MADRS score of 10 or below. Again, on the left-hand side is our core data, which you've seen before, a good improvement over time, but that improves much more after that second dose. Again, you see all the dose cells going up. Again, particularly the eight mg cell getting to a 67% response rate at day 57 with the one redosing. So again, this does support our decision to recommend the eight mg as the dose we're going to move forward into phase III overall. Next slide. Now we're going to look at our side effects. Again, like before, BPL-003 was generally well tolerated. The majority of our adverse events were characterized as mild or moderate. They were transient. They tended to resolve on the first day. Again, the most common side effects were mostly at site of administration in the nose. We had one serious drug-related adverse event. This was a person who had a history of not only depression, but panic, anxiety, and suicidal ideation, and sometime after dosing, she had a return of those symptoms, and it was decided for that reason to briefly hospitalize her. She was hospitalized, and for that reason, it became a serious adverse event. However, the side effect itself, the serious adverse event, did resolve the next day, so fortunately, the subject did have a resolution of her effect, but it was a hospitalization and therefore an SAE. Overall, though, the other side effects were mild to moderate, as I said, and again, our average time to discharge, like in the initial study, was within about two hours of dosing. The next slide. So where we are right now is that BPL-003 has demonstrated this rapid, robust, and durable therapeutic benefit for at least four months after two doses. In fact, again, you see this real improvement of response over the time of four months. It has very favorable tolerability and side-effect profile. So we do think that this Open-Label extension does show that this redosing paradigm can be very useful for improving response in people. We have shown in these two-dose administrations, a two-hour time in clinic can be expected, which is very similar to the SPRAVATO treatment paradigm. We have been fortunate to be granted Breakthrough Therapy Designation by the FDA in October of this year. And we do think our overall dataset supports advancement of eight-mg dosing into phase III. For upcoming key program events, we intend to have end-of-phase II meeting feedback from the FDA anticipated in the first quarter of next year. With positive feedback from the FDA, we hope to be able to initiate phase III studies in the second quarter of next year. With that, I'd like to turn things back over to Srini. Thank you, Rob. Let's now talk about the commercial opportunity for BPL-003. We'll talk about this in the context of the competitive landscape, starting with a brief discussion of SPRAVATO. Next slide, please. As many of you know, despite its slow start, SPRAVATO has become a successful key franchise for J&J. SPRAVATO achieved blockbuster status in 2024 and has already exceeded $1 billion in sales in the first three quarters of 2025. This product falls into the interventional psychiatry paradigm, where administration occurs in the doctor's office. Protocol for administration involves a drug being delivered intranasally by the patient under medical supervision, and then per label, the patient is then monitored for a period of two hours. At the end of that period, the patient can be discharged if they're medically and psychologically stable. There are approximately 5,000 clinics certified under the REMS to deliver SPRAVATO. Last year, approximately 50,000 patients were treated with SPRAVATO in the United States, resulting in about $930 million worth of sales. The challenge with SPRAVATO therapy is the sheer number of administrations that are needed to both induce a response and then maintain that efficacy. Induction occurs over the course of four weeks and involves two administrations per week, each in the doctor's office. Maintenance follows thereafter. The first four weeks of the maintenance period require administration every week, and then it's as needed thereafter. However, recent data suggests that most patients are getting SPRAVATO every week to two weeks to maintain the efficacy long term. Next slide, please. We believe BPL-003 and secondarily VLS-01 are uniquely suited to leverage the two-hour in-clinic paradigm established by SPRAVATO. We anticipate each visit for these two compounds to be very similar to the ones involving SPRAVATO, wherein there's a single administration and the resolution of physiological and psychological symptoms should occur in two hours or less. This paradigm addresses the scalability concerns that are present with longer duration products like psilocybin and LSD, and also addresses the complexity of same-day multi-dose paradigms. The benefits of the simplification include the ability for increased utilization by sites, and importantly, improving the quality of life for patients with TRD due to the much reduced burden, including travel, etc. Next slide, please. We're excited to come together as the Atai-backed lead with our focus on short-duration psychedelic therapies. We've been discussing BPL-003, of course, as it is the most advanced asset in the pipeline. And as noted previously, we anticipate initiating phase III next year after an end-of-phase II meeting. However, I'd like to take this opportunity to mention two other assets in our pipeline, namely VLS-01 and EMP-01. VLS-01 is a buccal form of DMT that's being developed for treatment-resistant depression. It's currently in a phase II-B trial, and we anticipate it reading out in the second half of next year. EMP-01 is an oral form of R-MDMA. It's currently being developed for social anxiety disorder. It's presently in a phase II-A trial, and we anticipate that trial reading out in the first quarter of next year. All right, with that, I will now open it up to questions. Operator. Thank you. To ask a question, please press star one on your telephone keypad. Again, that is star one to ask a question. And our first question comes from the line of Andrew Tsai with Jefferies. Please go ahead. Hey, congratulations on the data, and congrats on the overall execution this year, including the breakthrough designation. My first question is on the FDA meeting that you will have. Can you remind us the key questions that you'll be asking the agency, and more specifically, what kinds of alignment are you hoping to get as it relates to expediting the pathway? For instance, do you think you will ask if this phase II-B can be considered a pivotal study, or do you think you can file a rolling NDA? Because I think another sponsor just got a buy-in for that. Thank you. Thanks, Andrew, for the question and your kind words. It has been a very eventful and very positive year, so we're very excited about that ourselves. In terms of the specific questions that we'll be asking of the FDA, of course, we won't be divulging that. What we have committed to is in Q1 of 2026, providing an update on the aligned plan forward, the plan that's aligned with the agency once minutes are received. There has been some discussion around a single-trial approach that involves the phase II-B. The companies and other sponsors have said as much. Let's see how that goes. I mean, what we're not going to do is change our plan vis-à-vis a two-dose approach, I mean, a two-trial approach. So we will go ahead and kick off two phase III programs. Two phase III trials. It's just the details of the trials may differ a little bit depending on some of the discussion around that, so maybe Kevin, I'll let you pick it up from there if there's anything to add. Yeah, thanks, Srini. I think you've covered it really. I mean, as you say, there's lots to talk about there, and we're mainly aiming to align with the plan, and as you mentioned, I think we still need to run two phase III trials, and that's as much to do with the safety database as anything else, but the further details really, I think, are for the discussion, and although we've seen some movement from other sponsors, I think it's really certainly at that meeting that we'll get some clarity. Okay. Thanks. And my follow-up is that one case of suicidal ideation. Can you describe this patient, whether she had a meaningful efficacy response and which dose she was exactly on? And would you expect suicidal ideation to happen phase III blinded portion with the lower eight-week dose? Maybe I will start. So as you know, Andrew, suicidal ideation, etc., are unfortunately part of the clinical presentation of folks with depression, and certainly those with more severe forms of depression like TRD. So this was obviously quite prevalent in other programs, particularly the SPRAVATO program. There were multiple instances of suicidal ideation and actually behavior as well. So Rob, maybe I can hand it off to you for a bit more color on the patient. Yeah, happy to. So she, as many people with TRD, and as Srini just mentioned, she didn't have new suicidal ideation. In other words, this unfortunately was part and parcel of her illness and she actually had not so much a treatment plan as a treatment outline if she was feeling anxious, severely depressed, more severely depressed, or suicidal and she began to fear that she had these thoughts and actually contacted her clinician, and they activated a pre-existing thing that had happened before in her life, which is this brief hospitalization so for her, certainly an SAE, not backing away from that, but it wasn't a novel thing. Fortunately, she not only responded well to this intervention, she was having none of these thoughts within a day. And even when she was first having these ideas, she was initiating protective action, meaning she was asking her parents to help her get in the treatment. She was not trying to harm herself. She actively wanted not to. So she did well in that regard. She actually was a responder overall. She ultimately had an improvement in her depression. She was on the higher dose. She was on the 12 mg. So while we're analyzing this, I think it's important to know. I've done a lot of large studies in depression. This is part and parcel of the illness. We never want anyone to have these bad thoughts or actions, of course, but it literally does happen. So it wasn't a novel thing. It was a return to a prior thought pattern, as it were. She was an overall responder. She was on the higher dose. Fortunately, everything resolved with her. Great. Thanks for all the context and congratulations. Sure. Thank you. Thank you. Our next question comes from Ritu Baral with TD Cowen. Please go ahead. Good morning, guys. Congratulations on this data. I don't think that you guys specified whether you were going to pursue redosing in the phase III. If you are, are you going to, given the overall safety profile, would you redose with the 12? Would you redose with the 8, given what you've seen? If you could clarify how you're thinking about that in pivotal. And then I've got a follow-up. Thank you, Ritu. And it's good to hear from you. We have basically shelved the 12 at this point. Even if we did a redosing paradigm, it would be eight and eight. We did present some data that involved redosing the Open-Label study that also looked at 12, but these were all older things, basically designed prior to the phase II-B data. At this point, 12 is essentially shelved. The redosing paradigm is something that we're looking at. We're certainly going to have some discussions around that. The potential efficacy that I think one could argue we're leaving on the table by doing only a single dose, but there's just additional complexity if you do a multi-dose paradigm. These are some of the things that we're trading off at this point. I don't know, Kevin, if you had any additional thoughts on that. Yeah, no, thank you. I mean, I think you're absolutely right. I mean, that's interesting. We've seen this data, and we've seen the II-A Open-Label data, and it is encouraging that we can get maybe a bigger efficacy effect with two doses. But as you say, we need to trade that off against the complexity of coming in, let's say, two or three weeks after your first dose. And I think ultimately it'd be good to have a label that allows for either a single or two-dose induction and then the maintenance thereafter. But as you say, I think we're kind of sort of working through that at the moment and how exactly to implement that in our development program. But certainly, it's something that's on our mind. Yeah, I think one of the follow-ups to that. Oh, sorry. No, go ahead. Just one quick follow-up to that is, of course, this is something that's relatively short, right? It's a two-hour paradigm. So we're certainly open to that notion. This is different than a much longer acting compound, as an example. So the whole idea here is to fit in that SPRAVATO paradigm. Obviously, folks that are taking SPRAVATO are getting eight administrations over the course of four weeks, and they're getting very similar efficacy to BPL with a single dose. So we do have some flexibility in that regard. My follow-up is sort of a safety and commercial blended question. You mentioned that most patients were out in 90 minutes. Can you quantify for us what percentage of patients did not resolve outside of, say, that two-hour SPRAVATO timeframe or two and a half hours? Because I understand that SPRAVATO suites are booked for, I think, three hours at a time. And then the patient with the SAE, did she have any sort of adverse reaction during her first dose? I'm wondering just about intrapatient reactions. Okay. So I will let actually, Kevin, do you want to jump in on this? Yeah, sure. I can talk to Sydney the first part. I mean, in terms of the proportion, I mean, the majority are ready for discharge quite early on. I think two things to say. There is a proportion of 10%, maybe 15% who kind of required longer, sort of went beyond the two hours, and that is dose-dependent. So we did see differences between the 12 and the 8, with the 8 being better in terms of people being ready for discharge, and I think also we've maybe refined the scale that we used. We used a multi-faceted scale that looked at psychiatric effects, neurological effects, blood pressure, and a sort of global assessment by the clinician, is this person ready for discharge based on their adverse events, etc., and we've seen that some of those are more sensitive than others. And I think as we go forward into the next set of studies, we would refine that based on some of the learnings we've had from the first one. But what we do know is that some sort of structured assessment is going to be necessary. And so that's very much a topic of discussion. So I think that's. I think we're sort of pretty confident that the eight mg in particular has fewer of those people at the tail who are needing to stay around. But it's important to remember that even in compounds like SPRAVATO, there is a tail of people who are not ready at two hours. But the two hours is sort of the minimum time that people need to stay under assessment. Yeah, I think that's a really good point to highlight. Yeah. Sorry, sorry about that. I was just going to say, I think it's roughly 85% or so from the summary basis of approval, but I would need to go back on that, with SPRAVATO, that we're ready, so to speak, at two hours. So it is indeed kind of a floor. It's not by any means an upper limit. Sorry, Kevin. Then the intrapatient safety. Yeah. Yeah. Rob, do you want to take that, or do you? Yeah, either one. Yeah, sure. I mean, I can apply. Go ahead. Yeah. So this particular patient, you're right, this thing happened on the second dosing. And again, I think what you're seeing is probably the effect of this one individual who unfortunately has the suicidal ideation as part of her depressive condition. Followed over the course of four months, one of these things did happen. It didn't actually happen after the first dose. She wasn't, so it's not as if she had a bad effect and then another bad effect. She actually did relatively well in the first dosing period with some response. Didn't have more response after the second dosing, but had this one episode. So yeah, so it wasn't a phenomenon of her doing poorly and then doing worse. It was more this just happened over the course of the four-month period. Also, one thing to add to everybody's earlier answer, and Kevin had touched on this. It's important to note because this is how we differ from some of the other sponsors. A lot of people have talked about the duration of the psychedelic effect itself, which we certainly can talk about in a kind of a niche or a different context, but the psychedelic effect is very short with this agent. Also, with the other agents we're developing at the time, Beckley, the psychedelic effect is over with in almost literally everyone within an hour, and usually it's much shorter than that. What we're really looking at here is a dischargeability scale that we're still working on actively with the FDA to finalize it there. The psychedelic effect has to be over with, cardiovascular effects, blood pressure, heart rate, a neurologic exam, and then a global assessment of being ready to go home. All of those things have to go in the green, shall we say, for a person to be considered dischargeable. So that's where when Srini was saying there's about 85% within that window we're talking about, it literally means they're ready to go home. It doesn't mean that the people who aren't ready to go home are still having a psychedelic effect. That's just not the case. In this phase II study, we learned a lot of things. Some of it was that a lot of investigators really interpreted cardiovascular effects going away, that they're going totally back to baseline. Anytime you're checking with somebody's heart rate or something, that can be a condition where you want to be conservative, so you want to make sure. So we've seen the people who were tailing off, as it were. It was more they weren't quite considered back to baseline until just to let you know, after the 90-minute, the first check, the majority of the next check, which was at 120 minutes, people were ready. There were a few people that tailed out. A few people tailed out because they didn't have a ride home, literally. And the investigator said, "Well, that means they're not ready. We can't discharge them on their own. We're waiting for their other person." So we were being pretty conservative about being ready to go home. We'll work on that. We'll have that in the label. I can tell you from this early data, I feel fairly secure. We obviously have to look in phase III, but I'm pretty secure this part of the thing will become SPRAVATO-like, shall we say. So it's not that you have to keep people around for a long period of time. You can let them go when they're clear. We did look at 90 minutes in SPRAVATO. The first looked at 120 minutes. We will probably continue a look like that in our studies. So we think that the overall time to clinic will be relatively short. So sorry to jump back to the first half of your question, but I wanted to put a little more detail in there. That's awesome. Thank you so much for all the color. Very helpful. Our next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Please go ahead. Good morning, and congratulations on the data, and thank you for taking our questions. First question is, when you look at the responder and sort of remission rates from the core study and for those that were on the eight and 12 mg dose cohort, is there consistency in terms of those that were responders and remitters on day 57 in the core study and those that were responders and remitters in the OLEs at day 57, and I'm partially asking to see if the original responders and remitters were resilient. Yeah, that's great. Well, first of all, thank you for the question, Pete. That's a great question whether there was sustained response. I don't remember that data specifically. Kevin, I don't know if you have seen that. Yeah, I can say a little bit, and I'm sure Rob can say some more as well. I mean, so on average, we've looked at this, and we haven't done a specific looking at people who were defined as sustained responders algorithmically, but looking at the data, we do see that those who responded after the first dose are those indeed who have a sort of subsequent improvement after the second dose, so there is a group who I think, as with all drugs, may not respond to the drug at all, and those that do respond tend to respond to subsequent treatments as well. Yeah, this is Rob. I'll add to that. Kevin is completely right, and what we found so far, and this is a very preliminary analysis, that in essence, most people did respond. The vast majority of people did respond somewhat, so first part of your question is if you didn't meet much of a responder criteria in the first dosing, you still had a pretty good chance to have some response in the second dosing. But it appeared that, if anything, response predicted response. What I mean was, is if you were a relatively robust responder in the first dosing period, you really got a very good response in the second dose. That is part of what suggested us the one versus two-dose induction is at least worth thinking about because of that. There were definitely some people who just don't respond to this medication like any other medication. That's fortunately a very small number. Most people did have some effect on the second dose. If the people were a partial responder, they tended to be even a more robust responder on that second dose. All right. Thank you for that. And one follow-up question. Thinking about the phase III study designs, and I assume two will be conducted, will they follow the current paradigm of one against placebo and the other against a subclinical dose? And will retreatment be based on a clinical scale threshold? And are you thinking about monotherapy studies or allowing concomitant standard of care antidepressants? Thank you for taking my questions. Yeah, of course. So the more recent studies, the more recent phase III trials have not used a subtherapeutic dose paradigm. So we're not necessarily anticipating that. But of course, this is one of those questions for the FDA. So that's something that we'll obviously provide some color on. In terms of the Open-Label Extension with other sponsors, there have been some criteria. This is something that we are looking into as well. So we'll provide more color on that as well in the first quarter. And then, what was, oh, yeah, monotherapy versus adjunctive therapy, same kind of thing. I mean, this is kind of like Kevin was suggesting for the one versus two, that it'd be great to have the option of either. And the question is how to get there most efficiently in the context of two trials. We will take a look. I mean, do we do this in the context of these two trials? Do we do this in the context of an ANDA with a separate study? Still TBD. All right. Thanks, Dr. Srini. Congratulations once again. And thanks. Thank you. Our next question comes from the line of Harry Gillis with Berenberg. Please go ahead. Hi. Thank you very much for taking the questions and congrats on the data. You've been very clear that you're going to proceed with the eight mg dose, but I was wondering whether there's any indication or signs you may also examine a dose below eight mg, given the eight and 12 produced a similar effect? That's my first question. Thank you. Yeah, that's a good question. So the agency, as a general statement, does like to see a dose response, right? That's one of the ways that you address concerns around functional unblinding. And the example that I give here is the Compass data, right? The phase II-B, they had the subtherapeutic or subperceptual, I should say, 1 mg dose. But then they had 10 and 25. Both 10 and 25 were robustly psychedelic, but the 10 mg dose did not have the same degree of efficacy and indeed did not hit stat-sig, whereas the 25 mg dose did. So I think that is an important kind of data point. It's, again, another question for the agency how to proceed on something like that. Kevin, I don't know if you have anything to add on that point. No, I think you've covered it, Srini. I think clearly, looking at some of the other sponsors, that sort of mid-dose that is psychedelic but maybe less efficacious is a consistent paradigm that we see across a number of the other companies in phase III. And so I think that's certainly something that is likely to be on the cards. And we have really good data from phase I. We know the sort of subjective intensity and the PK, everything from 0.3 up to 14 mg has been studied. So I think we are in a good place to sort of pick a dose that is intermediate between 8 and 0 or 8 and 0.3 that meets those criteria. And as you say, that's something that's going to be coming up in the conversations with the regulators. Understood. That's really clear. Thanks. And then if I could just ask, so VLS-01 obviously had some delays. I was wondering, one, how that's progressing. Obviously, you've reiterated the readout in the second half of next year. And then as we think to BPL-003, just given everything we know, the FDA end of phase II meeting, potential phase III start, first half of next year, what's your current base case in terms of FDA filing and then eventual launch if everything goes to plan from here? So on the second point, on BPL-003 timeline to launch, we don't want to provide any color on that until we have clear guidance from the agency. So stay tuned on that point once we have the minutes in hand. On VLS-01, no change in guidance on that. We're looking for a readout in the second half of next year. Cool. Thank you very much, and congrats on the data. Thank you so much, Harry. And our next question comes from the line of Elemer Piros with Lucid Capital Markets. Please go ahead. Yes, good morning, everyone. So what I'd like to ask Srini and the team is how the non-completers were treated. I think in the first eight-week period, you identified 90% completion rate. I don't know what it was in the redosing paradigm and how you treated those who didn't make it to the end of the eight-week period. How we treated those? Okay. So let's see. Maybe Kevin, I don't know how best to handle that one. Obviously, we have attrition as we would in any study. So normally, it's something. In this case, we don't really model it. It's not like the primary analysis where you have an MMRM, etc. Here, it's more observed case. So the data that you have is the data that you have. But I don't know, Kevin, if there's anything else you can say on that. No, it's a very good question. And that's exactly right. So we obviously have a model where we're comparing statistically the three doses in the core study. But the analysis in the Open-Label is, as you say, observed data. So we had a similar withdrawal or dropout rate in the Open-Label, so about 90% up to the end. But then the values for each of those time points are actually the kind of observed data rather than fitting a model to that. Okay. Okay. Thank you. And Srinivas, I just wanted to make sure that you are still undecided whether it's going to be in a phase III, a one-dose or a two-dose paradigm at this stage. Correct. At this moment, we're not sure. I'd say that one of the big picture considerations is timeline of the primary endpoint, right? So obviously, with SPRAVATO, the primary endpoint was at four weeks, and that's in the original Transform 2 as well as the subsequent monotherapy sNDA trial. But the other sponsors seem to have six-week endpoints. So the inclination is that if it's a longer primary endpoint, there may be utility in doing a second dose. If it's a shorter one, perhaps a single dose may suffice. So that's, again, not something that we've discussed in detail yet, and we're just kind of considering these different things. And of course, we'll have that discussion with the agency. Yeah. Thank you very much. Thank you. Our next question comes from the line of Sumant Kulkarni with Canaccord Genuity. Please go ahead. Good morning. It's great to see you advancing the science and all the progress at AtaiBeckley, and thanks for taking our questions. Does the response on the 12-mg dose, especially on the retreatment part, have any read-throughs for frequency and time point of future dosing in terms of perhaps a ceiling effect? If not, what might explain the results in the 12-mg plus 12-mg dose versus the two other groups in the OLE? And then I have a follow-up. Hey, Sumant. Thank you very much for the question and the kind words. Yeah, I mean, it's an interesting one, right? So in the core study, we also highlighted that while statistically not different, the eight and 12, there was certainly a numerical benefit to the eight mg. And if you look at the adverse event table that was presented a while back, there was increased anxiety noted with the 12-mg dose. So unclear, to be perfectly honest with you, whether that anxiety is adversely impacting the efficacy that seemed downstream. It's certainly something that one could postulate. I mean, as you know, this is a single dose, the core study was a single administration trial. So normally, when the high dose in a normal study where it's a daily dose, and when the high dose looks worse than the mid-dose, usually that means someone dropped out along the way or what have you. But that wasn't the case with the core study because it was only a single dose. So that's interesting. I don't know that it materially impacts how we're thinking about the redosing paradigm, however. As noted, we're going to go with the eight and the eight and leave it at that. Good robust efficacy that was seen out. Indeed, for reasons that were interesting, I guess, or an observation that was interesting is that response remission criteria seem to be getting better as a function of time. Really do need to understand that. That may just be a result of dropouts, but I'm not certain on that. Anticipating redosing in kind of the eight- to 12-week time frame, and that's more or less consistent with what other sponsors are doing. Got it. Thanks. And then we appreciate that the actual time of psychedelic effect with BPL-003 is quite short here, limited to an hour or even less than that. But do you have or expect to have any analyses that attempt to parse out efficacy differences among patients depending on the differences in the duration of their actual psychedelic experience? Yeah, that's a great question. I mean, these are all the secondary analyses that we are looking forward to doing and making well, to making public, I should say. So you can anticipate more posters as well as publications that come out of this over time. Thank you. Of course. Our next question comes from the line of Patrick Trucchio with H.C. Wainwright. Please go ahead. Thanks. Good morning and congrats on the data. The first is just on the OLE data showing a deepening antidepressant effect over time. I was just wondering what your interpretation of that progressive increase in remission through day 57 post-redose, just your interpretation of that. And then as well, it sounds like what we're looking at is a paradigm where we have a more simplified dosing than SPRAVATO and as well, perhaps, as efficacious results. And so I'm just wondering, are we looking at a paradigm where we're redosing once quarterly? What is this dataset kind of pointing to you at as we're seeing this longer-term data mature? Yeah. I mean, we certainly anticipate something. Let me take the second question first, and maybe I'll hand it to Kevin on the first one, the progressive increase. But certainly, that's our conjecture, right, that this will be a significantly, I mean, substantially improved redosing paradigm compared to SPRAVATO. And yeah, as I mentioned in the talk itself, SPRAVATO is being redosed very frequently in many patients. It's at least once every two weeks. We would anticipate redosing closer to eight to 12 weeks, somewhere in that time frame with BPL. So substantially improvement in logistics for the patient and by extension, presumably, quality of life as well. Kevin, do you want to take the progressive increase bit or progressive improvement bit with the eight-mg dose? Yes, absolutely. I mean, it is interesting and sort of slightly different pattern compared to the core study, and I mean, we've had a couple of thoughts about that. I mean, the one is, of course, with bearing in mind that we are selecting a slightly different sample in the Open-Label. So there were sort of 15% of people who dropped out of the core study, and we had a few more who dropped out, who were eligible but then dropped out for various reasons going into the Open-Label, and so that, of course, selects for maybe a group that are more prone to response, but I think there are other interesting interpretations. I mean, one thing that we do hear is that there is increased social connectedness. People's scores are coming dow n quite significantly. And it may be that there's just a virtuous cycle setting up at that stage that they are participating more in activities of life, and that's creating its own feedback loop. So I think certainly something to understand in more detail. But I think as we look at that, that's our hope is that actually we start getting people into a situation where they're actually, over time, feeling better rather than feeling worse. Right. That's helpful, and then just as a follow-up, if you can talk about the safety profile a bit more, particularly as it relates to SPRAVATO and some of these other short-acting as well as longer-acting psychedelics that are in development. Yeah. I mean, I think big yeah, go ahead, Kevin. Yeah. I mean, I think on the face of it, the class looks very similar across a lot of the adverse events. So increases in blood pressure and heart rate, nausea and vomiting, we have rates that are quite similar to some of the other reported numbers out there. I think it's unique to this drug delivery is the nasal discomfort, which I think are rates that are we look at sort of things like nasal corticosteroids and other there are a few intranasal things out there. I think it comes somewhat with the territory. So nasal fullness is kind of generally a sense of irritation or itchiness. And so we sort of see some of that. The nasal-side pain, I think, is something I've been watching quite carefully. But that is in a small proportion and very short-lived. People tend to sort of have that pain go away really within an hour or two of dosing. So there hasn't been a lot that looks particularly different compared to the other psychedelics. It is somewhat different to the sort of dissociative drugs like ketamine and SPRAVATO in as much as dissociation sort of leaves people feeling fairly spaced out, whereas in this case, people are having maybe a sort of an intense experience that is less sedating, shall we say. But I think that's a lot of it's down to the sort of nature and the peak of the person's experience. And we spend a lot of time preparing people for that, monitoring people through that, and checking in on them afterwards to make sure that they sort of are sort of well and back into sort of life afterwards. So I suppose, I mean, we haven't seen anything that we're particularly concerned about. And it seems to be very much the pattern that we're seeing with these kinds of drugs, except in our case, of course, that the time that people experience those adverse events is shorter. So in terms of the amount of discomfort that someone has, we're talking about an hour or two every, let's say, 8 to 12 weeks as opposed to an hour or two every twice a week or once a week or 8 hours or 12 hours of a dose. So I think our sort of area under the curve for discomfort, if you will, is shorter, but otherwise no surprises. I just want to make a quick addendum here that the patient that actually we were discussing that had the serious adverse event actually was in the 0.3 mg dose arm initially, so essentially the functional placebo, and then got the 12 mg in the Open-Label. So just it is important to keep that in mind. That's helpful. Thank you so much. Yeah. Our next question comes from the line of Ami Fadia with Needham. Please go ahead. Hi, good morning. Thanks for taking my question and congrats on the continued progress that you guys are making this year. It's great to see. My question is just with regards to, I mean, clearly this data along with the phase II-A that you've recently disclosed indicates that with an induction dose and then with also a maintenance dose, we see subsequent improvement in response. So what are some of the considerations that may prevent you from or sort of that you would weigh in considering kind of an induction as well as a maintenance dose in phase III? And with regards to the maintenance dose, would you consider it to be sort of a timed every eight-week redosing, or would that be based on some other specific criteria, maybe the [audio distortion] score or some other criteria for the patient? And then I've got one other question. Sounds good. So yeah, in terms of the redosing, this is a discussion with the agency what they are looking to see. It seems like that the feedback we've gotten from other discussions is that the agency does have specific or particular views on how one approaches redosing. So that's something that, again, we'll be talking to the agency about. In terms of, I think the way I understood your first question was around the induction approach. Currently, correct me if I'm wrong, but it was obviously we're doing a single-dose induction now. There's certainly the notion that you're leaving some degree of efficacy on the table if you're doing only a single dose and you may want to do two doses to see if there's more. That's something that we're going to look into when that happens and how that looks in the phase III program is something that's still TBD. Of course, there's some precedent here. Compass is doing exactly that split across two different trials, as I'm sure you're aware. So there are 05 trials of single dose and there are 06 trials of two-dose induction. So again, something that we're looking into, as I mentioned previously, there's going to be some impact on the primary endpoint, whether it's a four-week or six-week endpoint is something that we'll also take under advisement as we think about one or two-dose paradigms. Understood. That's helpful. Secondly, with regards to the discharge timelines, it sounded like there might have been some patients who weren't quite ready. So my question, what I'm trying to understand is that what might have been the reasons? I think you mentioned one example where some patients just didn't have somebody to pick them up at the end of the timeframe, and so they weren't deemed discharge-ready. So in terms of the discussions with the FDA, what are some of the changes in the criteria or the questionnaire that you might explore changing to be able to sort of fit within the existing paradigm? Yeah. Sounds good. Hey, Rob, do you want to take that one? Yeah. So the agency is interested in several different parameters. That's a good question. I mean, one is, of course, the duration of the psychedelic effect. So that's one thing. A second thing is that the person is essentially physically back to normal. So that's more the physiologic characteristics like heart rate and blood pressure. A third thing is the neurological standing. The person can walk. They seem oriented to time and place. Different than the psychedelic effect, just more of like a neuromuscular effect going back to normal. And then finally, there's just a global assessment that the clinician thinks they're ready to go home. Where we found a lot of variance is that ready-to-go-home thing. And we'll define that better in our next trial. We were very open and conservative the first time. I think we found that the physiologic and the physical standpoint as well as the psychological standpoint seemed to work well. We haven't worked with the agency through this yet, but we did do this study, of course, under an approved IND, and that included this readiness-to-discharge scale. There wasn't a pre-existing in the literature scale, which you can't really have because each drug is different. So SPRAVATO has one, we'll have one. And I think that's what we'll ultimately work on is to be able to have that honed down so people know when people are ready to go home. The final thing about that, it's important. It's not as if you have to watch everyone until the last person in a phase III study design was ready to go home. This is much more how soon can you send someone home, which is like what happens with SPRAVATO in the clinic that Srini said earlier. The vast majority of people with SPRAVATO can go home within a couple of hours. There are a few people that aren't ready, and then they stay longer. So that's what we're expecting in the clinic. And that's what we'll work on, and we're actively going to work on that scale with the agency. Understood. Thank you. Hey, I will now hand the call back over to Dr. Rao for closing remarks. Thank you very much. Yeah. I mean, obviously very excited about these results, very excited also about this very first call, this very first webcast that is Atai Beckley. So as mentioned earlier, this has been a very eventful year. It's been a very good year for Atai overall. We've had lots of positive momentum over the course of the year. So clearly looking forward to continuing that in the next year with multiple readouts and multiple kind of important inflection points, not the least of which is the end of phase II meeting minutes that we've been talking about, but also the EMP-01 readout, which will be in the first quarter of next year, as well as the VLS-01 readout for the phase II-B in the second half of next year. So again, looking forward to following up with everyone as these various milestones are achieved. Thank you so much. Thank you again for joining us today. This does conclude today's presentation. You may now disconnect.