Hello, everyone, and welcome to the 6th Annual H.C. Wainwright Neuroperspectives Conference. My name is Patrick Trucchio. I'm a senior healthcare analyst at H.C. Wainwright. We have a robust agenda at the conference this year, with more than 30 companies presenting, with their full sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats with world-class KOLs on June 16th for the in-person portion of the conference, with broad CNS drug development focus across multiple indications, from depression and epilepsy to Alzheimer's disease and ALS, and featuring novel methods of drug delivery to the CNS. This is by far our strongest agenda ever. With that, it's my pleasure to introduce our next presenter, Srinivas Rao, CEO of Atai Life Sciences, a clinical stage biopharmaceutical company pioneering the development of highly effective mental health treatments to transform patient outcomes, with a pipeline focused on short duration psychedelics and pro-cognitive therapeutics. Maybe first, if we can just begin with an overview of Atai's pipeline strategy and how the recently announced merger with Beckley strengthens that strategy. Oh, Patrick, first of all, thank you very much for having me on. Yeah, it's actually a really exciting time for Atai. As you pointed out, there was just an announcement very recently, in fact, early Monday, I guess the 3rd or the 2nd, where we announced the acquisition of Beckley SciTech. That simplifies our pipeline pretty significantly. BPL-003 is an intranasal transmucosal formulation of 5-methoxy-DMT, also referred to as mebufotenin. That's being developed for treatment-resistant depression. That's in a phase 2B trial we'll be reading out soon. We have VLS-01, which is an oral transmucosal thin film formulation of DMT, dimethyltryptamine. That's also in treatment-resistant depression, and that'll be reading out in Q1 of 2026. We have an earlier stage asset called EMP-01. That's currently an oral formulation of R-MDMA, so the single enantiomer of MDMA. That is in a phase 2A trial for social anxiety disorder. We also have a non-psychedelic compound that's in development, and that is RL-007. That is being tested for cognitive impairment associated with schizophrenia. That trial will also be reading out here in the middle of the year. Those results are also forthcoming. Quite a bit going on. Yes, great. Okay, so maybe you can just walk us through the rationale for focusing on short duration psychedelics and how the two-hour in-clinic paradigm supports scalability. Yeah, I mean, so when we started with VLS-01, I mean. Hello, everyone, and welcome to the 6th Annual H.C. Wainwright Neuroperspectives Conference. My name is Patrick Trucchio. I'm a senior healthcare analyst at H.C. Wainwright. We have a robust agenda at the conference this year, with more than 30 companies presenting, with their full sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats with world-class KOLs on June 16th for the in-person portion of the conference, with broad CNS drug development focus across multiple indications, from depression and epilepsy to Alzheimer's disease and ALS, and featuring novel methods of drug delivery to the CNS. This is by far our strongest agenda ever. With that, it's my pleasure to introduce our next presenter, Srinivas Rao, CEO of Atai Life Sciences, a clinical stage biopharmaceutical company pioneering the development of highly effective mental health treatments to transform patient outcomes, with a pipeline focused on short duration psychedelics and pro-cognitive therapeutics. Maybe first, if we can just begin with an overview of Atai's pipeline strategy and how the recently announced merger with Beckley strengthens that strategy. Oh, Patrick, first of all, thank you very much for having me on. Yeah, it's actually a really exciting time for Atai. As you pointed out, there was just an announcement very recently, in fact, early Monday, I guess the 3rd or the 2nd, where we announced the acquisition of Beckley SciTech. That simplifies our pipeline pretty significantly. BPL-003 is an intranasal transmucosal formulation of 5-methoxy-DMT, also referred to as mebufotenin. That's being developed for treatment-resistant depression. That's in a phase 2B trial we'll be reading out soon. We have VLS-01, which is an oral transmucosal thin film formulation of DMT, dimethyltryptamine. That's also in treatment-resistant depression, and that'll be reading out in Q1 of 2026. We have an earlier stage asset called EMP-01. That's currently an oral formulation of R-MDMA, so the single enantiomer of MDMA. That's in a phase 2A trial for social anxiety disorder. We also have a non-psychedelic compound that's in development, and that is RL-007. That is being tested for cognitive impairment associated with schizophrenia. That trial will also be reading out here in the middle of the year. Those results are also forthcoming. Quite a bit going on. Yes, great. Okay, so maybe you can just walk us through the rationale for focusing on short duration psychedelics and how the two-hour in-clinic paradigm supports scalability. Yeah, I mean, so when we started with VLS-01, I mean, the idea was, the assumption was, I should say, that J&J would be able to make this work from a commercial perspective. And, you know, if you go to the label for Spravato, essentially it means, you know, the way it's outlined is you come in, you're dosed, it's an intranasal administration, then you're monitored for two hours, it's, you know, per label, then you're assessed, and if you're stable medically, then you're allowed, you're discharged. And, you know, that's the paradigm. It's interventional psychiatry. It's really the first, you know, pharmacotherapy that was actually on label. I mean, ketamine presumably was also sort of the precursor to that, but this is actually on label and being, you know, was developed by J&J. We were right in the assumption that J&J would be able to figure this out. It was off to a slow start, to be sure. Spravato did not get going for a little while, but they did hit blockbuster status last year. And, you know, in the U.S., is about worldwide was blockbuster. U.S. was about $930 million, and that was based on around 50,000 patients. So they have cracked the code, if you will, in terms of reimbursement. They basically provided a cookbook for the, you know, for the clinical sites to on how to do this. So we wanted something that would essentially be a drag and drop into that paradigm. So we talked a little bit about each visit for Spravato, but the challenge with Spravato is you just have a lot of them. So it is an induction and maintenance paradigm. Induction is basically four to eight weeks. It is 12 visits during the first eight weeks, which is a lot. You know, you're going in, you can assume it's at least all in four hours. I mean, you got two hours of monitoring, but at the very least, you're going to have an hour on either side. It's almost like another job is what some people have said. Then maintenance beyond the induction period, per label is, you know, roughly every two weeks or less. 60% of patients that get Spravato actually are taking it every week. Again, you're losing one day every week with this. Psychedelics have more durable efficacy based on all the results with psilocybin and other compounds to date. They have a more durable efficacy profile than ketamine and esketamine. That's what we're anticipating with these short durations. Something that has the best elements of, you know, it's got the short visit in a doctor's office, but has the durability. That is what we've been targeting. Right, terrific. Maybe moving on to BPL-003. This is for treatment-resistant depression, alcohol use disorder, AUD. What are your expectations for the upcoming phase 2B readout in TRD, and how are you going to define success in that data? Yeah, so the trial, if you look at it, is very similar to the trial that Compass did a number of years ago now, actually, with psilocybin or COMP360 in treatment-resistant depression. It's a high dose, as it were. I mean, the top dose is 12 mg. There's an intermediate dose of 8 mg, and there's a subperceptual dose of 0.3 mg. In this case, it's 195 patients all in. The 8 mg dose is a smaller arm. So that's essentially what the trial is, you know, how it looks. The endpoint is the primary endpoint's at four weeks, a single administration, then four weeks later is a primary endpoint, and then there's a blinded follow-up that goes on for another four weeks, a total of eight weeks. That's the layout of the trial, very much modeled on, again, on Compass's trial. You know, what we're looking for are sort of similar effects. I mean, that's basically what I can say without getting into, you know, powering assumptions, but that's basically what we're looking for. I mentioned that the, you know, the transaction that we announced last week regarding Beckley and the acquisition thereof. That is contingent upon success in this trial, which is, you know, hitting Satsiga on the primary endpoint. Right. Assuming that we see the positive data that we're expecting, what are the anticipated next steps for advancing BPL-003 into phase 3? What might that trial look like? What might the clinical development path look like? Yeah, so obviously the first thing is parsing that data, understanding what that data is telling us. It would then be an end of phase 2 meeting, assuming that the results support continued development, of course, and then we'd be kicking off phase 3. It's hard to know or hard to really guide on what that phase 3 trial will look like in detail. If you look at it kind of big picture, all of the phase 3 programs in general look pretty similar, right? There's a dose or two, and, you know, they're separated by, you know, two to three weeks. The primary is somewhere between four and six weeks, and there's usually 12 weeks of blinded follow-up. That's basically what these trials all look like. The devil's always in the details. Now, the other devil, or the other detail here is the open label bit and the redosing elements. We talked about induction. What does maintenance look like? That is, you know, something that different companies are approaching differently. I mean, certainly, you know, some companies are focused like Compass, I think, is focusing on roughly three-week, I mean, sorry, three-month redosing schedule. You know, that is something that we will need to look at the data first, understand what the decay curves on efficacy look like, and then we can make some assumptions about how frequently one should anticipate redosing. Right. Now, there's, you know, this question around functional and blinding that I think comes up actually across neuropsychiatry. It's come up more specifically around psychedelics. How is this question being addressed in both the phase 2B trial and as well, you know, potential pivotal program? Yeah, as you point out, functional unblinding is kind of rampant across neuropsychiatric drug development. I mean, if you're in a randomized control trial that involves, you know, olanzapine or fluoxetine or paroxetine, and you're getting that or placebo, I can pretty much guarantee you'll know which one you got, you know, just depending on, just based on the side effects. Certainly, psychedelic compounds have a more robust unblinding effect. There's no doubt about that. The way that you basically can assess the impact of functional unblinding is sort of twofold. Number one is you're looking for dose response, right? You know, just a concrete example of that is Compass. In their phase 2B, they looked at 1 mg, which is subperceptual, 10 mg, then 25 mg. What they found is a 25 mg dose provided robust efficacy, statistically significant efficacy. The 10 mg dose, even though it was quite psych, it was robustly psychedelic, did not have the same efficacy. That tells you that it's something above and beyond the psychedelic effect itself that's driving it. There's an underlying mechanism for the efficacy. That's the first mechanism. The second is to actually look at durability. Folks with treatment-resistant depression, if you give them, if there's some kind of intervention that's performed on them, you'll get efficacy. I mean, that's true of any kind of neuropsychiatric indication. It typically decays right back to placebo. These are treatment-resistant, right? Things, some perturbation may happen, and it might feel better, but then it goes back to baseline. You really want to see what the, you know, how long it takes to revert back to depression. Those are the two elements that we're really looking for. As I described, the BPL trial actually does incorporate both of those. Right. And so then how do you see BPL-003 differentiating from GH001 and other short-acting psychedelics, both in terms of clinical profile and commercial model? Yeah, so I mean, there really are only two programs that are designed to fit squarely in the Spravato paradigm. What, again, going back to that, it's a single administration, monitor for two hours or so, and then discharge. The only two programs that do that are BPL-003 and VLS-01. Other programs are either longer, like, you know, psilocybin's longer, certainly LSD is significantly longer. Others, like GH, as you pointed out, are more complex because they involve an individual dosing paradigm. It's up to three administrations in a given day. It involves dosing, and now each administration is shorter. I think it was around 15 minutes, 20 minutes in terms of total duration of psychedelic effect. Each individual one is shorter, but then you monitor the patient, you ask the patient essentially through a questionnaire how intense that experience was. At the top of the hour, you can redose again. That is a different paradigm. It is a more, you know, involved paradigm from the site's perspective. It can be longer, right? It can be, you know, three hours or so. Particularly when you factor in kind of practicalities, it will not necessarily be completely on the hour, like clockwork. Right. What's the potential for the label over time in alcohol use disorder's potential? Are there other, you know, bipolar depression, PPD? What is the potential ultimately for BPL-003? I think it's a great question, and it also ties into VLS-01, how the two sort of play together, right? I mean, the nice thing about psychedelics so far has been that they are transdiagnostic in many ways. There are these underlying network dysfunctions in a range of affective disorder, you know, developmental network and reward networks, et cetera. These compounds have impacts on aberrant activity in those networks, and they seem to resolve that, normalize that. Again, that means you can get efficacy across different things. Anxiety has been looked at, GAD has been looked at by MindMed, of course, but they're also looking at depression. Certainly that's something. Substance use disorders have come up repeatedly with these compounds. LSD had some very good data a long time ago around opioid use disorder. Obviously, the AUD data with BPL-003 was also quite compelling, even though it was open label. Yeah, there's a number of different avenues that we could pursue once we have these data in hand, certainly. It's a good segue then into VLS-01. This is DMT for TRD. Maybe you could first talk about VLS, what differentiates it from other DMT approaches currently in development, particularly its, you know, buccal film formulation. Yeah, so I mean, I think that's a major point of differentiation. There are the, we really engineered this for, you know, patient acceptability and provider acceptability. This is, you know, we really wanted to actually have a formulation that essentially no one had major problems with. I mean, you know, there's a subset of patients that don't like stuff going up their nose, right? That's evident with Spravato. I mean, there's, you know, some% of people just don't like that. We wanted something that was super simple that the providers could get, would be very comfortable with, and the patients would find easy to use as well. We have essentially like a Listerine strip. It's basically placed on the inside cheek surface. It sticks to that surface, and it dissolves over time, roughly 10 minutes plus minus. It's how long it takes to dissolve. It delivers the drug, again, transmucosally across that buccal membrane. That's a point of differentiation. It's a complex formulation, as it turns out. It's very difficult. You don't have a lot of surface area to play with. We talked about GH Research, right? Right. That's hailed into the lung. You have roughly a football field worth of absorptive area in that context. BPL-003, it's intranasal. It's a transmucosal, you know, you get the nasal membrane. It's a number of, I mean, it's, you know, several square centimeters. When you're talking about these, you know, the buccal, it's, you know, a couple of square centimeters. A very small absorptive area. It's challenging to get it to work, but we're very happy with the results that we've seen. Right. Can you walk us through the phase 2 Illumina trial design? What do you hope to learn from this when it reads out? I think it's in the first quarter of next year, 2026. Yep, that's correct. That's when it's reading out. You know, we obviously are, you know, will be privy to the data from BPL-003. We wanted to go in a slightly different direction with VLS, going back to this induction and maintenance paradigm, and see what the impact of having two doses would be. That's what differentiates this. Now, you're probably familiar with Compass's phase 3 program. Their first trial is a single dose, and their second trial is two doses. Here we want to understand that in phase 2. We have two administrations two weeks apart. Primary endpoint is at four weeks. Blinded follow-up, 12 weeks in total. Then there's a re-randomization where we actually look at 120 versus 60. We get some dose response data as well. It's slightly different design, two arms in the first bit instead of doing three, just to facilitate recruitment and everything. Then we get the dosing data in a re-randomization, 14 weeks after the initial dose. If we look ahead, you know, several years into the future, VLS-01 and BPL-003 are both successful. Do you see them serving complementary roles in a commercial setting? Or, you know, would they become almost, you know, competitors or competing for the same use cases? I mean, I think it's a little bit early to say. Of course, they're both being looked at at TRD at the moment. There's obviously opportunity to change the subsets, different subsets of MDD depending upon the results. I'm not that concerned, even if they're both after TRD. I mean, the TRD market is huge. As I mentioned, the $930 million in the U.S. was based on 50,000 patients out of 3 million with treatment-resistant depression in the U.S. That's, it is a large population. You know, the pharmacologies are different. Subjectively, these compounds seem to be different, and we need to be more definitive on that. You know, we'll get that data with phase 2s. How that may translate to different patients or different patient subtypes, of course, is something to be seen. I think there's a lot of different paths that we can take going forward. Right. Great. Maybe just moving on then to RL-007. This is in cognitive impairment associated with schizophrenia or CIAS. Maybe you could talk about this program, just kind of give us the background on the program, how it came to be part of the pipeline, and then talk a little bit about the phase 2B top-line data that's expected in mid-2025. Yeah. So this is a really interesting compound that was basically developed at Allergan a number of years ago. And, you know, this was something that was, normal drugs are usually kind of pharmacologically characterized, right? So when you're doing the screening, you look at in vitro receptor screens and things. This one was actually phenotypically characterized. So they were put, it was put into animals, and then they were put, you know, given different sort of challenges or tasks, et cetera. So what they found here is that at lower doses, there's a pro-cognitive signal. And at higher doses, the cognitive signal went away, but it became more of an analgesic. And so there was a decision to move after, move into the pain space with this compound. But they kept looking at the pro-cognitive effects. In fact, they did one phase one trial that was focused on cognition. It was actually a scopolamine challenge trial. Scopolamine, you know, is a muscarinic antagonist that actually causes cognitive impairments. And when they gave this compound, you could actually reverse the elements of those cognitive impairments, and you could actually reverse some of the EEG changes that are caused by, you know, the, by the scopolamine. That was kind of interesting. In a larger phase two trial in diabetic peripheral neuropathic pain, the primaries obviously were analgesia, but they did look at, as an exploratory endpoint, cognition, and they found sort of the same pattern. It was verbal memory and other things were improved. There was another phase one in that was not pharmacologically challenged in any way, but they also showed improvements there. That was the backstory. Again, this was at the lower doses, there was a pro-cognitive signal. The serum concentrations actually lined up with the animal data. It was a very compelling story. When Allergan merged, you know, with AbbVie and everything, this was something that kind of got put on the shelf. The team at Allergan really wanted to see this move forward, and they essentially spun it out. We brought this into Atai a number of years ago at this point. You know, again, very interested in areas of large unmet medical need, and certainly cognitive impairment in schizophrenia is one of those. That is what prompted us to begin that development program. The trial that we've got, that'll be reading out very soon, is actually a robust 234-patient study looking at placebo versus 20 mg versus 40 mg of RL-007. The primary endpoint is the MCCB, the MATRICS Consensus Cognitive Battery. We'll be looking at that at six weeks. Yeah, I mean, it's going to be a very interesting result. We're looking forward to that, you know, this has been a long time coming, this trial, so on these results. Right. Interesting. And then just on EMP-01 for social anxiety disorder, what prompted the decision to pursue R-MDMA for social anxiety disorder? And how do you view its differentiation from racemic MDMA? Yeah, actually, the initial, you know, the kind of initial hypothesis around this is that, you know, R and S MDMA are very different pharmacologically. S MDMA looks much more like a stimulant. We knew that MDMA had pretty pronounced stimulant activity and cardiovascular effects. The idea was that we could get a kind of gentler, potentially safer version of that by pursuing just the R. When we actually tested in phase one, we found that yes, indeed, it is much less of a stimulant, but the subjective effects were very different than anticipated. It does, in fact, have intactogenic effects, but it also has psychedelic effects, but that were not normal psychedelic effects. It was not quite like a psilocybin, but it also was not quite like MDMA. That is what got us intrigued by this. We wanted to, you know, think about where we could deploy that. Long story short, there is some literature around MDMA in social anxiety disorder in a particular subset, which is in folks with autism. Decided to look at social anxiety disorder and, you know, based on that result, you know, look at this compound. You know, there were some measures like self-compassion, et cetera, that got better with this. There was, you know, so there were specific elements that really looked like they could be beneficial for this indication. That's why we decided to conduct a phase two wave study there. Certainly an area of large unmet medical needs, significantly larger actually than depression. Actually became more, you know, thrust more into the limelight, if you will, because of COVID, you know, because of all the social isolation. These are effects that are going to be persistent for some time, particularly in the younger folks that kind of, you know, lost some years of socialization there. Really an interesting indication, not something that's been mined particularly well recently. I mean, certainly there's no psychedelic that's going after this. The last approvals were, you know, the early 2000s. Again, that's what really kind of got us interested in this and why we're pursuing that phase two way. Can you tell us what you're hoping to learn from the phase two trial that's underway in the U.K. and if the data are positive? Just the timing, is it first quarter 2026? Correct. It's first quarter 2026 using a regulatory endpoint, the Liebowitz Social Anxiety Scale, looking to see, you know, how this compound in using only this, you know, psychological support, what kind of efficacy we can see there on, again, on a regulatory endpoint. How does that compare to SSRIs, et cetera? That'll be obviously supportive for our decision-making as we move that asset forward. I mean, we are also looking at reformulations of that potentially to shorten the duration of it. Those are all things that are currently ongoing. If we just move to the discovery portion of the pipeline, can you update us on the progress with your non-hallucinogenic 5-HT2A agonist program and what the therapeutic profile it is that you're targeting with those compounds? Yeah. So I mean, we've developed, let's see, I think we've certainly, you know, synthesized somewhere north of 700 different compounds that are both psychedelic and non-psychedelic, reputatively so, I should say. How do you assess this? You normally put it into animal models like rodent models and look for head twitch. How good a predictor head twitch is for the human psychedelic experience is open to debate. You know, we don't know that these are non-hal, but, you know, we're interested in actually developing them. We do have a really good mechanistic understanding at this point of what drives head twitch. You know, what we want to do is essentially, you know, get these into humans over the course of the next year, year and a half, and actually assess what these compounds look like. They're very different than some of the other compounds that have been developed that are putatively non-hal. Because we use a computational chemistry approach initially, these are not tryptamine structures. They're very different. You know, we have a number of different scaffolds that we're playing with that have somewhat different properties. Really excited to get this, both, you know, certainly the non-hal compounds and reputatively non-hal compounds into humans soon. What would you say investors are missing about the Atai story? Yeah, I mean, there's been a couple of things. I mean, the story has changed a lot over time, right? Initially we were much more of a hub-and-spoke kind of arrangement, and that was complicated for everybody involved, including investors, right? Because we had minority ownership in different companies or majority ownership, et cetera. Now it's a much simpler story, right? Now it's, we have a pipeline and, you know, we own 100% except for RL-007, but everything else we own 100% of. It's a very straightforward story to tell. Also, we were, you know, some years out from readouts. Last year, for example, there were no readouts last year other than phase one. That also kind of, you know, blunted enthusiasm for it. It's going to be a very exciting year for Atai. We've got these two readouts coming up now. We've just announced this transaction with Beckley so that the BPL readout again is, you know, quote unquote, Atai Beckley's. It's ours, if you will. And then we have three other phase two readouts coming up. It's going to be a very exciting year. Right. Terrific. It is an exciting year. Thank you so much, as always, Srinivas, for taking the time to speak to us. We are looking forward to all the readouts. Thank you to Atai for attending the conference. Thanks to everyone for being with us at the conference this year. Have a great rest of your day and a great rest of your conference.