It's my pleasure to introduce our next presenter, Srinivas Rao, CEO of AtaiBeckley, a clinical stage biopharmaceutical company pioneering development of highly effective mental health treatments to transform patient outcomes with a pipeline that's focused on short-duration psychedelics and pro-cognitive therapeutics. Just to get us started, for those investors who are maybe less familiar with the story, can you provide an overview of where the company is today and your vision for positioning AtaiBeckley across the interventional psychiatry space? Yeah, absolutely. Well, first of all, just a quick thank you to you, Patrick, for inviting me to this conference. I really do appreciate it. Yeah, just a quick summary of AtaiBeckley. We are a company that's focused on mental health. We currently have a pipeline of three psychedelic compounds in late clinical- stage development. Our lead is something called BPL-003. I can describe it in a little bit more detail subsequently. That's entering phase III. We just actually initiated our phase III program. We have VLS-01 that is also in treatment-resistant depression. That is going to be wrapping up a phase II-B later this year in the fourth quarter. Finally, we have EMP-01, which just completed a phase II-A trial. We read out some of those results a little earlier this year. Great. Just regarding the lead program, BPL-003, this is intranasal mebufotenin benzoate. Why is the intranasal formulation the right lead product profile for TRD? How do we think of the differentiation of BPL-003 versus other compounds of a similar mechanism and development? Yeah. There's a specific objective that we wanted to meet with both BPL-003 and VLS-01, that was something that gives you a psychedelic duration that is as long as possible within a two-hour window. Now, why are we picking two hours? Well, that's because that is the window that's been established by SPRAVATO. If you go to SPRAVATO's label, SPRAVATO is esketamine, by the way, for the treatment of treatment-resistant depression. If you look at its label, the way it works is you go to the doctor's office, you're dosed, you have to be monitored for two hours, if medically cleared, you can go home. A priori, when we were developing these compounds, it was something that our objective was to kind of flush out as much of that as possible. Certainly not be over and really making sure that the physiological as well as psychological effects are wrapped up well within that period of time. We also wanted to avoid the alternative. The other issue, which is if the pharmacokinetics are too rapid, you get a very different profile. It's not the same sort of psychedelic effect that you get when there's a more gradual increase. The intranasal route of administration really splits the difference beautifully. You get a Tmax in on the order of 15 minutes, but essentially all of the psychedelic effects kind of wrap up in 90 minutes, and certainly by two hours. Indeed, when we had a discussion recently with the FDA at the end of phase II meeting, the FDA was comfortable with our ability to just discharge our patients in the phase III trials, assuming they met discharge criteria at two hours. VLS-01 again is very similar. Right. That's really helpful. What are the most important outcomes from the FDA end-of-phase II meeting for BPL-003? Yeah, I think clear alignment on what the phase III program looks like and what the two trials look like. Obviously, the other element here was understanding what the safety database needs to be. We're talking about intermittent therapies here, and just kind of jumping ahead, we're talking about something that we redose on the order of every 8- 12 weeks. The underlying condition is a chronic one. Treatment-resistant depression is a chronic one. In general, for chronic indications, there is a desire to have a certain amount of exposure over a period of time and understand what the impacts are. That was a very fruitful discussion as well. Right. Maybe you can walk us through more specifically the phase III program, the ReConnection-1 and ReConnection-2 trial designs, and what distinct question does each trial answers? Yeah, absolutely. ReConnection-1 is replicating in some ways the phase II. It's a single administration during induction, in essence. You give a single dose. In this case, you follow the patients out for 12 weeks. The primary endpoint is at four weeks. We're looking at three different doses. We're looking at true placebo versus 4 mg versus 8 mg. The 4 mg dose is intentionally a dose that has psychedelic effects, but those effects are not as robust as what you see with the 8 mg dose. The idea is to understand dose ranging a little bit. We have an open-label extension that extends for another year, and in this case, the patients start out with an 8 mg administration, and then, depending on how they are doing, they can get dosed. Not only it's every 12 weeks, but if they need it, they can get dosed on an eight-week schedule. That's what the open-label extension looks like. The ReConnection-1 has around 340 - 350 patients. ReConnection-2 is a bit smaller. It's about 230 patients. Here we're asking a different question. We're asking what does a two-dose induction paradigm look like vis-à-vis magnitude of efficacy as well as durability? We have two doses of 8 mg at day one and then day 14. Primary endpoint's day 28, and then again, follow the patients out for a subsequent eight weeks. Open-label extension looks exactly the same. This one's, again, around 230 patients. Right. That's interesting. Maybe you can tell us why a week four MADRS for the primary endpoint, with this drug, following a day two onset and potentially longer durability. Why is that the right timeframe? There's a couple of reasons for this. First of all, there's historical precedence, right? SPRAVATO has had an approval, the core approval for adjunctive use as well as subsequent sNDA for monotherapy that was based on a four-week endpoint, so there's good precedence for it. Moreover, the phase II-B actually had a four-week endpoint, and in general, one wants to change as little as possible between phase II and phase III. Other folks have gone from change their time point primarily in one case from week three to week six. Anything that changes things introduces additional clinical risk. The idea here is to match as much as possible the phase II. In the phase III program, how should we think about the placebo control design, inclusion of a low-dose comparator, and functional unblinding? Those are kind of interrelated. A true placebo is what the agency's currently recommending. In previous studies, including in the BPL-003 phase II, there was a sub-perceptual dose. Compass used that in both their phase II and one of their phase IIIs. Ultimately, the utility of that, ostensibly, it was for functional unblinding because basically you're telling the patient that they will get a dose of the drug. It could be a sub-perceptual dose, but you will get a dose. In reality, it's unclear what benefit it really confers. The way that the agency is addressing questions of unblinding at this point is through dose response. You can actually see that in the phase IIs, in particular for Compass as well as Definium. There were doses in the case of Compass, a 10 mg dose of psilocybin, which was psychedelic, robustly so, but did not have the same degree of efficacy. Similarly, in Definium's GAD trial, 100 µg was effective. 50 µg, despite being psychedelic, was not effective. It allows you to make a conclusion that indeed it's not just the psychedelic effect that is causing the efficacy. It is something that's underlying that. Of course, durability is an important element here as well. Those are the main things that we're looking at. We are doing another dose ranging in essence, and that is by looking at two doses in the second trial, right? There's two shots on goal in terms of dose ranging. That makes sense. Maybe you can talk a little bit more about the dosing. I think from the phase II-B, we've selected the 8 mg dose. What did you learn from the 4 mg, 8 mg, and 12 mg data? What did this teach you about the drug and the therapeutic window, and why did we go forward with the 8 mg dose? Yeah. It's interesting because we view AtaiBeckley as really being as developing second-generation psychedelic molecules. What we mean by that is that we have novel formulations, right? In the case of BPL-003, it's intranasal. It's a dry powder intranasal transmucosal. Then, in the case of VLS-01, it is a transmucosal but oral thin film. What that meant is we really did not have a sense of what the doses should be because it's never been dosed that way. These compounds have never really been administered that way. That's in distinction to something like psilocybin, where there's an existing literature around 10 mg, 25 mg, and a little bit higher, and similarly with LSD. In those cases, you had a pretty good idea where to start. In our case, we did not. With BPL-003, the two doses that were picked for the phase II were 8 mg and 12 mg, as you said. Both of those doses actually had very similar psychedelic effects, and the question was slightly different. It's is there a benefit to actually going to 12 mg versus 8 mg? Is there a therapeutic index benefit, despite them having sort of the same degree of psychedelic effects? Indeed, what we found in the phase II was that, paradoxically, the 8 mg was numerically superior to the 12 mg. In fact, looking at the data in totality, you can sort of conclude that the 12 mg is probably a little high. There was some anxiety that was associated with it, et cetera, so that may have contributed to the somewhat lower numerical efficacy that was seen there. The adverse events were higher. There was a dose response, so they were a little higher with 12 mg, so it was a very clear and very simple decision to make to go back to 8 mg. 4 mg, we do have additional data from the phase I trial. We also have some open- label data, et cetera. We do know that it's psychedelic. We also know that it's not nearly as robust a psychedelic as 8 mg, and it's much shorter in duration. I think it provides a good control for this dose response element that we're looking at. Right. That's helpful. Maybe we can talk about the safety profile and tolerability. What matters most for BPL-003? Should we be looking at sort of cardiovascular anxiety, dissociation-like effects? What is it that we should be looking for here to give us confidence in this safety profile? Yeah. I think most of what we're seeing is basically what you see with the class, right? Excuse me. Whether it's nausea, vomiting, whether it's headache, or indeed cardiovascular parameters like pulse elevations and blood pressure increases, these are class phenomena. We do have some additional stuff that's due to route of administration. There was some nasal irritation. All of it was mild, moderate, and pretty much resolved by the time the psychedelic effects became apparent. I think the way to think about this is almost like an area under the curve, right? If you think about something like psilocybin or LSD, where the effects are much longer. The psychedelic effects are much longer. The pharmacokinetics are much longer. Well, the blood pressure effects and everything else are much longer as well. In the case of LSD, it could be six, eight hours, maybe longer, that the patient is under some degree of cardiac stress. Right? In the case of BPL-003, it's very short-lived. How does concomitant SSRIs or standard of care antidepressants or other antidepressants affect BPL-003 efficacy and safety? Why is the, I guess, the part four cohort strategically important? The core phase III trials currently are monotherapy. Again, just like the phase II-B. The cohort four is alluding to a separate trial that we've got ongoing that's an open- label, phase II-A. We did actually do a cohort that was a single administration of a drug in conjunction with a limited list of SSRIs and SNRIs. We actually found no real difference in subjective effects or efficacy. In fact, numerically, efficacy was a little bit better than in the case of monotherapy. We have a subsequent cohort that we'll be reading out at the end of this year that's looking at two doses of 8 mg on top of a background of SSRIs. The idea here is to really generate a data set that supports the safety and efficacy of adjunctive use. It could be part of the data set that we use to ultimately get a label that looks like that. Right. That's helpful. Then just if we go back to the phase III program, what are you trying to learn from the 52-week OLE and individualized eight or 12-week retreatment intervals? How will you distinguish relapse prevention, maintenance of remission, and retreatment response in the long-term data set? Yeah. We haven't really gotten into the details yet of the criteria that we're going to be using. Obviously, we've had alignment with the agency on that, but just for competitive reasons, we're not really talking about it. I'd say if you step back and look at most of the competitors, particularly the first-generation molecules, the focus has been on 12-week redose. There's a reason for that. These are long days. They're long days for the patient, they're long days for the site, and they can be quite challenging. We don't have any difference. If you compare phase II to phase II, the durability that we saw with BPL-003 was identical to that seen with psilocybin. Right. In fact, numerically, the durability was a little bit better. No concerns about durability despite the short duration of the psychedelic effect. Because of the short duration, we actually have the opportunity to help people that are struggling a little bit and need a dose that's a little bit sooner. That's why we have the option of an eight-week dosing. Again, no specific issues. In fact, the data looks really good, very robust despite the short duration. Again, gives the opportunity for the patient, gives a choice for the patient and the provider, to get a dose a little bit earlier than the other compounds, just to maintain the same. What do you expect the acute monitoring period to look like commercially, and what data supports that operational model? Well, again, we're going to generate the data in phase III, obviously. The idea here is, in fact, a label that looks a lot like SPRAVATO in terms of total duration of monitoring. In general, psychedelics do require. Well, the agency has required additional monitoring for psychedelics, right? Having a person in the room is something that the agency is currently looking for, certainly in the clinical trials. How that'll translate to the real world, I think, is TBD. What is actually going to be in the REMS? I don't know. We'll presumably have some clarity on that with the approval of COMP360 and Definium's DT120 in time here. I think we'll get some clarity on what is actually going to be required. Right now, the expectation is that there will be someone in the room. With BPL as well as VLS-01, as I mentioned, the psychedelic duration is short. More importantly, the duration of an intense psychedelic experience is very short. In the case of BPL, it's like 30 minutes to 45 minutes. That's compared to the same sort of intensity with psilocybin, it may be several hours. Certainly, with LSD, it's a number of hours. The need for monitoring is less, and I think we've got a better chance of ultimately getting away from having to have someone in the room. Of course, that's going to ultimately end up being a discussion with the agency reviewing the phase III data or indeed reviewing post-marketing data. Right. That's helpful. How should we think about the necessary launch infrastructure for BPL-003 if it's approved? Does the approval of the longer-acting psychedelics, like COMP360, does that help? Absolutely. There can be advantages to being a first mover. There can be some significant advantages to not being a first mover. Getting providers comfortable with psychedelics, I think is going to take a little bit of effort, and I think both Compass and Definium will establish that. I think they'll both be successful in that regard. In terms of the commercial footprint, I think it's really interesting that if you look at the current SPRAVATO sales, currently the run rate for SPRAVATO is over $2 billion for this year. About 75%-80% of those revenues are coming from on the order of 700 clinics. They're fairly concentrated. I think it's around 20 states, for example. It's a very concentrated commercial footprint. We're talking a launch, even with 1,000 sites, on the order of 50 to 100 reps. This is great. This is something that a small company can easily implement. It's something that we're really excited about. Great. Just moving on to VLS-01, the Elumina program. This reads out in the fourth quarter of this year. What does VLS-01 need to show in this program to move forward into phase III? Yeah. Ostensibly, what you need to show is the minimal clinically important difference on the MADRS right? Which is typically viewed as kind of a three-point delta versus a placebo. I think in general, there's a number of parameters that we're going to be looking at. Obviously, efficacy at the primary endpoint, like we talked about, the potential MCID. Durability is going to be important and understanding what the durability looks like and how that compares. As well as tolerability, right? How does the side effect profile of this compare to other compounds, I think is going to be really important. All of these parameters are going to be taken under consideration as we make decisions on how to advance the program. Great. Then just on EMP-01, maybe you can tell us a little bit more about this program. It's showed some signals in social anxiety disorder. What would the next controlled study need to prove, and what's the status of this program? Yeah. EMP-01 is currently an oral formulation of R-MDMA. MDMA is indeed a racemate. The S- enantiomer has very strong amphetamine-like properties that causes norepinephrine and dopamine release. The R- enantiomer is much more serotonergic. When we started the development of this, our expectation was that most of the beneficial effects would be actually in the R- enantiomer. We put it into a phase I. We actually found some really interesting properties. We were able to push the dose higher because we got rid of the bad actor, and in so doing, we actually found a very different profile, one that was psychedelic, but also entactogenic and kind of different than either MDMA or psilocybin, for example. That's why we were excited. We wanted to test this in a subsequent trial, in a phase II trial in patients. Could have done something easy, like depression or something, but wanted to really explore a new indication. We chose social anxiety disorder for a range of reasons, not the least of which is it's a huge unmet medical need, really something that people are not looking at closely, at least in the psychedelic space at the moment. We did a double-blind, placebo-controlled, 80-patient study and looked at primary improvement of safety, focused on the key endpoint of the so-called LSAS, which is a regulatory endpoint, the Liebowitz Social Anxiety Scale. Importantly, that's a behavioral scale. You ask the patient about how they would respond in different hypothetical scenarios. These could be like talking to a stranger, going to a party. They're hypothetical conditions. It's important that these are not symptoms, right? Symptoms can change immediately. You alluded to that with depression, right? With BPL-003, you got an improvement at 24 hours. You can't assess behavior that quickly. We had a short study, two doses of EMP-01. In six weeks, we found effects on the LSAS that were comparable to what you see with an SSRI at 12 weeks of continuous dosing. There was a nice slope. There's no expectation the slope would suddenly flatten at six weeks if we had run this trial out. We anticipate that we'd continue and get much greater effects. Indeed, when you ask the patient subjectively how do they think they'd react to these different scenarios, the effect size was huge, about 0.84. We are, again, very happy with this. Still reviewing some data. We'll be providing additional guidance on how we want to advance this over the next couple of months here. Maybe just one on the earlier stage pipeline. What does this look like, and how does perhaps a non-hallucinogenic program fit into the investment thesis long term? Yeah. It's a pretty robust discovery program. We don't get a chance to talk about it a lot. It actually came from a collaboration with a company called Cyclica, it was AI-based drug discovery. Essentially, looking for novel structures. We've synthesized probably well north of 700 compounds at this point, tested in vivo and in vitro, many of those compounds. I think we have a really good understanding of the 5-HT2AR receptor, how these different molecules have to bind within, what leads to putative hallucinogenic effects versus none. Of course, with this all pre-clinical, we're looking at the head twitch response. In terms of where these could go, I think this is a different paradigm than the psychedelics, right? It's a means of obtaining high levels of neuroplasticity, much greater than one would see with an SSRI or an augmentation strategy. In the absence of traditional psychedelic effects. That could be something that is a new paradigm, completely different than psychedelics, but could be useful for certain patients, or useful in the same patients, but in a different stage of their disease. Maybe just as a last question, with the cash runway extending into 2029, how should we think about the main catalysts over the next 12 - 18 months? What should investors be looking for, and is there anything that you think might be less appreciated by investors? Yeah. I think the main readout is really VLS-01's phase II-B, which will be in the fourth quarter of this year, as we discussed. Of course, once we have that data in hand, assuming it's positive, we would then move that forward into phase III. There'd be an end of phase II meeting next year, and a kickoff with a phase III in the roughly 18-month kind of time point. Of course, with BPL, we are initiating the phase III trials now. We also do have that other readout with the phase II-A later this year. There's a couple of things that are ongoing there. Again, we'll provide a bit more color on EMP-01 as well. Terrific. Well, Srini, thank you so much. Always a pleasure to catch up. AtaiBeckley, I think, has one of the most exciting pipelines in all of neuropsychiatry. Really looking forward to these next readouts and trials. Thank you to everyone for joining us for the conference. Have a great rest of your day and conference. Thank you.