Welcome to the last day of our Jefferies healthcare conference. I'm Andrew Tai, Senior Biotech Analyst at Jefferies. Thanks for joining in, and it's my pleasure to have the Atai team with me. To my direct left is Srinivas, CEO, and to his left is Kevin Craig, CMO. Welcome, both of you. Thank you very much for having us. As an introduction, I think we all know you're pursuing psychedelics in general. Maybe to start off, talk about what makes you differentiated from the other psychedelic companies out there in the interest of time, and walk us through milestones we can expect over the next 6- 12 months. Yeah, no, that sounds good. Our focus from the outset was really to have products that are short psychedelic duration that mimic in many ways Spravato. I think that's really where we started with the internal asset, which is VLS-01, and we just completed a transaction last week, a merger with Beckley Psytech. In fact, we're now AtaiBeckley. Their asset was also very much like that. Essentially coming into a doctor's office, getting administered the product, two hours of monitoring, and then medical assessment and potential discharge. Very much like Spravato. Other psychedelics that are in current development, and certainly later stage development at the moment, are longer duration, whether that's psilocybin or LSD, or have much more complex administration protocols. Understood. Milestones? Yeah, we got a lot. We got a lot going on over the next year. We guided that we submitted an end-of-phase II meeting request. We'll provide guidance on the results of that meeting in the 1st quarter of next year. That's for the lead asset that's called BPL-003. That's going to enter phase III. We'll initiate those trials at the 2nd quarter of next year, depending on the results of the EOP2, of course. We have EMP-01, which is our earliest stage clinical asset that'll be we'll have a readout on the phase II-A trial that actually just concluded enrollment. We just announced that. Oh, nice. We'll have top line results from that trial in social anxiety disorder. Later in the year, 2nd half of the year, we'll have the results of VLS-01, our phase II-B trial in treatment-resistant depression. Great. Congratulations again on the merger. I should have. Thank you. In the beginning said AtaiBeckley. You're not AtaiBeckley, so my apologies. Maybe let's dig into your lead compound, BPL-003, which is the 5-MeO-DMT, where you've generated some really nice set of positive phase II data. Maybe tell us what makes you really excited about the data that you've generated so far. I mean, you've looked at induction dosing, you looked at maintenance dosing. Feel free to say what you want to say about that. Yes. I mean, stepping back, one of the questions with short duration psychedelics was, what is the impact of that short duration on the magnitude of efficacy that you're seeing acutely? Also, what is the impact on durability? The first data set that we saw with psychedelics in treatment-resistant depression was the psilocybin data, I mean, the psilocybin data from Compass. They ran a very nice, very robust clinical study. They showed good efficacy. They came on pretty quickly, but then it was durable out to 6-12 weeks, depending on the patient. The question was, if we cut that psychedelic duration from four to six hours down to roughly an hour, what does that do to that efficacy? I think what we've demonstrated in that phase II-B trial of BPL-003 is that there was really no obvious impact in terms of magnitude of efficacy or durability. That was a really important finding, and that's what made that data set really exciting. I think what I also like that, well, we don't truly know what efficacy looks like with a single dose because, well, the durability part aspect, because out to week eight, when we think about the MADRS curves, it doesn't rebound back. You haven't really teased out a single dose durability. What do you think exactly is the dosing profile at the end of the day in the real world? Yeah, I can take that. I mean, I think we've looked at this. If you look at Compass's data and other data as well, there'll be subgroups within there. There are clearly some people, let's call it a quarter of patients who are sustained responders. They get significantly better, and they stay well for as long as we've measured. There is another group who get a lot better, but by week eight or week 12, we're starting to see that their MADRS scores are creeping up again. I think those are a group who you'd think about redosing. Of course, there are also the remitters and the responders. There may be people who have a significant benefit, but are not yet in remission. There's another group who I think would justify a 2nd dose or a 3rd dose or further doses. Because I do think that you want to get everyone, as many people as possible, into remission, and that probably will take more than one dose. The durability, how long for each individual patient, how long do you need to go before you have another dose, I think is going to be very individual. We really need that one year, at least open label data to begin to understand the most common treatment profiles and what they'll look like. That makes sense. That one year open label data, would that be part of the phase III, to be clear? That's right. Yeah. In fact, unlike many studies, our open label portion is doing double time. Of course, we need to capture the safety data, but we also need to work out the dose regimen. How do we label? Is it every eight weeks? Is it every 12 weeks? What proportion of patients need a dose once a year? I think that's something that we're going to also be solving for in our open label. Okay, that's great. Maybe give us a frame of reference. I think in your data set, I'm seeing 65-70% remission rates to, I forget the time point, but maybe week 16 or something. That's correct. Yeah. That's month four. Maybe help us frame what do other drugs show at a similar time frame. Yeah. So, I think, I mean, I'd sort of really frame this in terms of the acute response rates or remission rates and then the long-term remissions rates. If you think about MDD, for example, this is general major depression, and you look at the SSRI data, there about 30%-45% of people are in remission at six weeks. That's a good proportion. Of course, there's a group that aren't. If you look at treatment-resistant depression, much tougher. If you look at this Spravato monotherapy data, for example, about 22% are in remission at four weeks. We saw with BPL-003 about 25%. I think it's really tough in the treatment-resistant group to get into remission quickly. If you look at the longer data, it's quite a different picture. For an MDD patient, by one year, about 70% are in remission. In TRD, I mean, Janssen have got some very nice real-world data that showed that it takes about 14 months to get 50% of people into remission. You're getting that incremental benefit over time. Each treatment is just bringing people closer to remission. I do think that there's going to be more doses to get people, as many people as possible, well. Understood. If I were to ask you on a blended basis, there's different types of responders to BPL, let's just say this was approved in the real world, on average, what would be the number of doses per year you would think? Yeah, that's a really good question that I think we really need the data for. I mean, we can see that out to eight weeks in our case and out to, say, 12 weeks in Compass's case seems to be, on average, a time frame where people are staying well, maybe beginning to turn and needing another dose. You could imagine four to five, maybe six doses a year. Great. That's a big difference, obviously, than Spravato. Spravato is an incredibly effective drug for many patients, and it's obviously been a game changer. Just induction, it's an induction and maintenance protocol, and just induction is eight doses over four weeks. It's a big time commitment for the patient, obviously a time commitment for the provider. Maintenance from there on out, many people are getting it long term, every week to two weeks. That's, again, very difficult. I mean, you're basically losing a day per week or every other week. We're looking at something that markedly changes that. Got it. Thanks. Now you're meeting with FDA in Q4. You'll come back to the street in Q1 or early 2026. Can you share what you're thinking about these two phase III studies, how they could look in terms of the study design, dose, and so forth? I mean, big picture, if you look across the programs, I think there's a lot of commonality between all of the phase III programs that are currently being prosecuted. It is one or two doses. It is a primary, typically six weeks. There is like 12 weeks of blinded follow-up. There is this open label bit beyond that. They all look very similar to that. There are a number of questions that we have within that, four weeks to six weeks endpoint, one or two dose induction, things like that that we are going to have discussions with the agency on. I do not know. I think that's exactly right. I think the other thing that we recognize both from the guidance and from the other sponsored protocols in phase III is that we probably need a mid-dose that is psychedelic to again mitigate some of the unblinding questions. At least one of the trials will have that. I think the stance on an active control has changed a bit, and now certainly our preference is for a placebo control in both groups. I think that mid-dose then mitigates some of the concerns and allowing you to really compare to placebo. Got it. Aside from discussing the phase III trial design with the FDA in this meeting, you do have a breakthrough designation too. I forgot to mention that. Does it make sense? What are the other important questions you want to ask the FDA? I can imagine maybe you want to ask them, was this phase II-B study considered a pivotal study so that maybe only one out of two phase III studies is enough for you to file? Would that be a possibility? Yeah. Look, I mean, I think our default is that we need to do two trials. I think there's maybe a question around that, but of course, we need a safety database that is of a certain size. I think we see ourselves needing to run two trials in any event. Now, whether we only need one for pivotal approval and whether we can use something else, those are conversations to have. I think at the moment, we have to assume two trials. there any other discussion points that you can think of that are important to relate back to the street? I don't think there's anything else that I'd consider material. There's obviously some differences. I mean, some of the questions now are really nailing down what we're going to need for the approval. We know what we need to start the phase III. We're ready there. That's not the question. It's really, what else do we need? There are other clinical studies that are common. TQT, what do we want to do? Do we need to do things like that, et cetera? There is invariably some preclinical that needs to get banged out. I mean, obviously, CARC studies and things. We have some ideas on that. These are things that we'll be asking. These are sort of the normal run-of-the-mill type questions that one would ask at another phase II. Okay. Maybe one last question to that. I mean, we know another player in the market wants to expedite their program. I think maybe they agreed to a rolling submission. Is that something you want to discuss yourself? How do you approach the FDA landscape, basically? I mean, big picture, breakthrough designation does give you the option for a rolling submission. I think that part is relatively straightforward. There have been some discussions with the current leadership at the FDA on making the process a little bit more efficient, which I think we all applaud. Making sure that if it's a rolling submission, people do the diligence on their sections rapidly and on time, as opposed to waiting for the clinical section or what have you. I think all of those things are playing in general favor. I think that's what at least must be part of why Compass re-guided. Great. Ultimately, if this was approved once again, why would someone use Spravato over your drug? I mean, Spravato is doing $2 billion run rate. Look, I mean, I think Spravato is a fantastic treatment, and it really is the first interventional treatment for treatment-resistant depression. From my perspective, I think it's really good to provide more treatment options to patients. I mean, we know from other medicines and classes that for reasons that we don't yet understand, some people respond to one mechanism and not to another. Sometimes they respond to one drug within a mechanism and not another. I think patient options is a big part of this. It may be that there are groups of people who are responding well to Spravato would stay on that. I think it's good to have more arrows in the quiver. As we think about the 5-MeO-DMT landscape, there is another player that you've effectively leapfrogged, actually. Can you talk about why you have a more robust program at the end of the day? I mean, there's a couple of reasons. The other program is using an inhaled formulation. It's essentially vaporized, and then that product is then inhaled. One of the things that seems to be a stumbling block for them has been the tox. That's consistent with public guidance. The pulmonary division does tend to be relatively conservative. They don't like things going into the lung. I've had some experience in previous lives around that with an inhaled loxapine product. That was a single administration, realistically, in your lifetime. There was a lot of additional work that needed to be done. In the case of this other product, it's GH Research, just to it is up, at least in their phase II, the protocol they employed there was up to three doses in a given day. It was once a month there on out for six months. It's up to 18 doses in that context. Not saying that people got that many, but theoretically, that was your upper limit. That, I could see, would provoke a reaction from the agency to do significantly more tox. I think that's part of it. I think the administration protocol was certainly more complex. That's one of the things that we wanted to get away from. Make it simple. Make it just like what the doctors are already used to with Spravato. You guys have patents around this, to be clear? We do, actually. We have issued patents in the United States. We have patents on the salt itself, the drug product itself. Actually, we just got an issue once a couple of days ago on broad claims on transmucosal delivery. Oh, wow. Okay. Speaking of safety, anything to mention for BPL-003? Anything in terms of risks, as we think about risks, phase III risks? Yeah. I think, I mean, the first thing to say is that the product was well tolerated. We had more than 99% of the adverse events were mild or moderate. We got really what we've seen in the class. We got those effects. Nausea and vomiting, increased heart rate and blood pressure, headache, which we see across all of the compounds. We had some more specific items around the route of delivery. We had this nasal discomfort, which, again, I think is understandable. People complained of a nasal fullness, or sometimes they had some nasal pain. It was fairly short-lived, but again, I think expected. I mean, more broadly, obviously, we've been watching very carefully the risk for suicidality. I think that's a very difficult one to pass because, of course, we don't exclude patients with suicidal thoughts or intentions coming into the trial. It's absolutely part of the illness that we're studying. That fluctuates over time, and people do develop stronger thoughts of suicidality at times. I think that's the one that has been something to watch carefully. In our study, we had, if anything, a slight preponderance, and it was very low in the control arm. I think we're very satisfied at the moment that there isn't an increased risk. This was the first dataset that we've received. Of course, that's something that we need to watch very carefully. Great. Phase III starting, two of them, Q2 of next year. When could we get data? If you're not willing to share, how long did it take phase II-B to complete? Phase II- B was first patient dose was October 23, I believe. That sounds right. The top line results were July 25. I'm not trying to be cagey, where once we have a bit more clarity on the phase III program after the end of phase II meeting, our plan is to provide a little bit more color around that, particularly around timing. Right now, just because there are a number of variables from trial size to some of the other details around inclusion and exclusion, we're kind of avoiding it. Yep. Thank you. Last question around this asset. To me, it's de-risk now. Does it make sense to pursue other indications with BPL-003? I think you pursued alcohol use disorder before. It was a small study. Yeah. I think that's interesting. Right now, our heads are down on getting through the phase III program. We are looking at other indications. We also have other programs. How we divvy it up is something that we're obviously exploring. Okay. Moving on to your other program for social anxiety, your R-MDMA, the right isomer of MDMA. That has data in Q1 of 2026. To me, it's robustly designed. I think your stock can move. Maybe talk about the design of that study, how many doses, and ultimately, what is high-quality efficacy to you? Yeah. Yeah. Let me just describe the study to start with. We had done, obviously, the phase I study, and we picked a dose that had robust effects. In this study, we're taking patients with social anxiety disorder. We've picked a fairly severe group. It's a common illness. It's one of the most common psychiatric illnesses. We've gone for using the standardized scale, the one on which the SSRIs were approved. It's called the LSAS or the Liebowitz Social Anxiety Scale. We're taking people with a cutoff of at least 70. Quite a severe group. If they're on any antidepressant medication, they are washed out. They are randomized to either 225 mg of EMP-01 or placebo. We give two doses one month apart. The primary endpoint, again, is the LSAS. That's taken at day 43 or week six. We have a short two-week safety follow-up after that. High-quality data to you would be maybe give us a reference what the LSAS reductions are for SSRIs or benzos or beta blockers? Yeah, sure. I think the first thing to say, this is a proof of concept study as we understand this indication. The primary endpoint is safety, but we're obviously looking at efficacy scales in secondary endpoints. If you look at SSRIs, some of the SSRIs are approved for social anxiety disorder. What we saw, there was a decrease in the LSAS of around 10-15 points. I think we've got to be better than that, given that this, although intermittent, does involve a dosing paradigm. I do think that people will be started on SSRIs as a first stop. We want to take a more severe group. If you think of 10-15 points, better than that would be important. I think if we're thinking about effect sizes, Cohen's d effect sizes, again, the SSRIs are about 0.3. 0.4-0.6 would be within a range that we'd be happy with. Clearly, I mean, there's a study that was done, a very small open-label study, where they looked at R-MDMA, sorry, MDMA in patients with autism and social anxiety disorder. They showed an effect size of over one. That was small. I think we're likely to come down to a more reasonable size with a bigger study. Wow. Okay. Thanks for that. We'll wait for that data readout. You have another one, VLS-01 DMT compound with data 2nd half 2026. To me, it's also robustly designed, this time for treatment, back to treatment-resistant depression. What do you want to see in terms of efficacy for that compound for a no-go, no-go type of decision? Yeah, I think we've, again, I think you're right. We've designed a study that I think is well powered. Here, we're testing two doses as a two-dose induction model. I think the idea being that we want to get people as well as they can be quickly and then move to a maintenance phase. We've got a dose, and then two weeks later, a 2nd dose. There's the 12-week follow-up period off that last dose to look at the treatment trajectories before we re-randomize and we look at a third dose. I think we would like to see the effects that we see with Compass and with BPL. We're talking about a five to six-point MADRS reduction. I think critical to that is also the safety profile. I think we really went with a dose that was robustly psychedelic but well tolerated. We actually tested a higher dose that we stepped away from. I would like to see a clean safety profile. Certainly, in phase I, we had very low rates of nausea, no vomiting, limited psychiatric distress or anything like that or anxiety. It is going to be the combination of both the safety profile and the efficacy profile. That is the ballpark I think we are looking for. Okay. Yeah, go ahead. Yeah, I was going to say, I mean, we are testing something a bit different on this with VLS, and that was by design. We're looking at two-dose induction. I think there is, we don't have double-blind placebo-controlled data on two-dose induction yet. In other words, literally two doses separated by a couple of weeks. The expectation is we are leaving some efficacy on the table by not doing that. I mean, just stepping back for a moment, BPL-003 at its four-week endpoint had the same magnitude of efficacy in terms of MADRS drop, etc., as Spravato did. Spravato had eight doses. The question is, if we had done another dose of BPL, could we have improved on that? That's something that we'll look at with VLS. There's different ways of assessing improvements, of course. One would be the magnitude of change. The other one really is durability. We do have 12 weeks of durability data, as Kevin mentioned. Of course, the other metric or the other dimension here is safety. Of course, that's pretty important to us, and we'll be looking at that. It's always the risk-benefit on any of these things. How tolerable is it for the amount of efficacy that you're seeing? Thanks. Maybe last minute, you do have three assets you're working on right now in the clinic. Can we expect you to introduce more in 2026? God, I hope not. No, I mean, we are, obviously, the company was really founded around business development. We will remain opportunistic. Our focus right now is obviously execution, getting these phase III programs up and running, getting these phase II results on time, etc. We will take it from there. Okay. Very good. Yeah. What I would say very quickly is we do have an interesting discovery program. We've recently got a NIDA grant, which I think has been hugely helpful. It's non-dilutive funding. We're obviously progressing those compounds. Some of those are non-hallucinogenic 5-HT2 agonists. I think I'm very excited about those as well. They won't be in the clinic in 2026, but maybe soon thereafter. Okay. We'll discuss that next time. Thank you very much for your time. All right. All right. Thanks for your.