Hi everyone, my name is Athena Chin, and I am an associate at TD Cowen. Thank you all for joining us this afternoon. Here we have Srini Rao, CEO of Atai Life Sciences, who will be providing a corporate update following Atai's corporate presentation. I will be moderating a Q&A and also opening up the floor for any questions. Srini, please take it away.
All right, thanks, Athena. I am going to stand, I think. Thank you very much, everyone. Appreciate your time. Standard forward-looking statements, so we'll, you know, standard disclaimer rather, there will be some forward-looking statements in my talk. Just big picture, I just want to give you kind of a lay of the land with Atai. Essentially, we are focused on mental health and really looking at indications with large unmet medical needs in that space. Now, if you think about mental health writ large, it's one of the largest, you know, medical, you know, global health burdens amongst all chronic diseases. It's basically one out of two people that in the course of their lifetime will be affected by a mental health disorder. Depression, anxiety, et cetera, being the most common of those. We have currently five assets in our pipeline.
We have four phase II readouts over the course of the next year, which I'll walk through. On the depression side, we have a specific focus on, in terms of our psychedelic drugs, and that's really this two-hour window that's been established by Spravato. I'll give you a little bit more color on that. We do have, as I mentioned, multiple phase II readouts over the course of the next year, next 12 months, actually. We recently completed a raise, insider-led raise. We currently have cash, we have a runway in 2027 that includes cash and cash equivalents, as well as marketable securities. This is the management team, and there have been some changes since the beginning of this year. I'm a co-founder of Atai, and I recently stepped into the role of Chief Executive Officer.
There are basically, we had a shift in terms of our focus and our approach. Originally, we had a much more complex business model. We had entities that were partially owned. There was an element of it that was more of like an investment company. We've really shifted into a more traditional biotech role, and that was, you know, well suited for my background. In addition, Kevin Craig and Glenn Short have been promoted to Chief Medical and Chief Scientific Officer roles, respectively. Gerd Kochendoerfer, who's someone that I worked with in the past, has come on board as the Chief Operating Officer. Really happy with the current team, really well set for the next year's worth of execution. This is an overview of our pipeline. The top there, the psychedelic programs that are listed are VLS-01.
I'll talk a bit more about that, but that's based on DMT and an enzyme methyltryptamine, pursuing treatment-resistant depression, again, in phase II at this point. EMP-01 is our MDMA, so it's one of the enantiomers of MDMA. I won't go into any detail on that today, but we basically found that in a phase I trial, the profile of this compound was markedly different than MDMA, by eliminating the one enantiomer, which made it very interesting. Spent some time thinking about indications, ultimately settled on social anxiety disorder, large unmet medical need, but not a lot of companies pursuing that. We have strategic investments, again, that are sort of reminiscent of our older model, one of which was actually announced about a year ago. That's Beckley Psytech. And we own about a third of that company. And they have a late-stage asset or mid-stage asset, I should say, BPL-003.
That's what was really the basis of our enthusiasm, our excitement for this strategic investment. I'll walk through that in a little bit more detail. They also have a backup compound, essentially, ELE-101, which is an IV formulation of psilocin. If a patient or subject is given psilocybin orally, you end up with psilocin. Psilocybin is actually a pro drug. Finally, we do have a non-psychedelic asset as well. We had a broader mandate around mental health originally, and we have, you know, managed to sort of step away from that, really kind of focusing on the psychedelic assets. This program is actually the largest of the phase II trials that's currently ongoing and will be reading out in the middle of this year. This is kind of a, you know, just kind of stepping through all our milestones.
BPL-003 will be reading out again, you know, in a June sort of timeframe, right on top of RL-007. These two are kind of neck and neck at the moment. VLS-01 is going to be reading out in the first quarter of next year, as is EMP-01. Three of these are actually phase II-B type trials. In other words, we would go to the agency afterwards and, you know, we are prepping for phase III. The only exception to that is EMP-01. That is an earlier stage trial. It's a proof of concept, again, going into a different indication. We will also be shifting, we're planning on shifting formulations and route of administration before going into the next study. Okay, let's talk a little bit about short-duration psychedelics. Let me start by just kind of giving you an overview and differentiating the two assets.
Because again, we've got two things going on in treatment-resistant depression, BPL-003 and VLS-01. Pharmacologically, you know, these are based on two separate molecules. BPL-003 is mebufotenin, also referred to as 5-MeO-DMT. And VLS-01, as I mentioned, is N,N-dimethyltryptamine, or just referred to as DMT. Pharmacologically, very different compounds. They, 5-MeO-DMT actually is much more of a 5-HT1A agonist. 2A is what's thought to really drive the psychedelic effects, but certainly they're modulated by this other pharmacology. Interestingly enough, there's a lot of, you know, if you look at trip reports and things like that, there are differences in terms of subjective effects that are noted between DMT and 5-MeO-DMT. We have seen some differences even in the two respective phase I trials. We haven't run about, you know, a comparative study, but there are some differences that we noted, which is interesting.
What that means in terms of efficacy, of course, we don't know, and that'll take some time to really ascertain. Both formulations are nasal, I mean, are transdermal, or transmucosal rather. BPL-003 is a nasal spray, so it's a dry powder nasal spray. And VLS-01 is a buccal film. Essentially, this is like a Listerine strip, thin film. You put it on the inside on the cheek surface, and it dissolves over the course of 10 minutes or so. Both treatment durations are around, I mean, both compounds or both products give you psychedelic effects that last about, well, a little less than two hours. They're fully resolved by about two hours. Again, we'll talk about that on the next slide, really focusing on what the Spravato paradigm, as I've mentioned. Both of these are in phase II. BPL obviously is further along.
INDs are open for both assets and good intellectual property on both assets as well. Okay, Spravato, again, was sort of our North Star as we were developing VLS-01. This, you know, it was a couple of years ago, obviously. We anticipated that J&J would be able to build up a commercial infrastructure to make Spravato a success. Indeed, that's exactly what they've done, right? Last year in the United States, Spravato was used in about 50,000 patients. In the U.S., it was about $930 million. Worldwide, it was just over $1 billion. They had a slow start. They launched into COVID, but importantly, they didn't really have all of the commercial infrastructure set up. It took them time. They've done it now. They have about 4,500 clinics that have been through the REMS process that are REMS registered, essentially.
You know, they plan on expanding that further over the course of the next couple of years. The label for Spravato is essentially that you come in, you are dosed, you're monitored for two hours, and assuming the patient is stable, they're then discharged. There's very limited monitoring other than assessing safety during that period of time. VLS-01 was designed to fall into that paradigm. We wanted it to be something that a site could drag and drop into their existing infrastructure. BPL-003 sort of had convergence and evolution, if you will. It's the same kind of paradigm. It's around two hours, as I mentioned. If you think about assets that are in depression in particular that are fitting into that, there's really ourselves. I mean, there's really only ourselves. I mean, there's no other company that's pursuing that. There is another company that's doing 5-MeO-DMT.
It's a company called GH Research. They're using a multi-dose strategy. It's up to three doses in a day. You're dosed, you're monitored. It's much shorter. Each psychedelic effect is shorter. It's about 30 minutes, plus minus. You're assessed. If you didn't have a full psychedelic experience, you were redosed at a higher dose level. That can happen three times. My understanding is it can only happen on the hour. Realistically, the shortest is around three hours somewhere in that timeframe. It can be longer if things don't go exactly to clockwork. Of course, there's additional monitoring that's required over the course of, you know, that period of time. Psilocybin is longer, you know, on the order of six hours.
MDMA is longer still, as an LSD finally is really the longest and, you know, could actually get into the realm where it's outside of a normal business day. That's, you know, that was something that we tended to avoid and again, really focus on super short duration. Spravato's out there. It's got a two-hour duration. Why do we need something else? Spravato, each individual visit is actually pretty straightforward. It's just that there's a lot of them. If you look at the label for induction, it's eight weeks. It's twice a week for the first four weeks and once a week for the subsequent four weeks. It's 12 visits. You come into the doctor's office, as I mentioned, you're dosed, you're assessed, and then you're discharged. You're not driving home.
If you think about it in your own life, going there twice a week, you're probably not going to be doing too much work after the fact. This is just a lot. With a psychedelic compound, I mean, we need the results, obviously, but even with a short duration, we anticipate over the course of four to six weeks, up to eight weeks, you'd maybe have one, two administrations, somewhere in that ballpark. Markedly easier for the patient, markedly increased bandwidth or throughput for the sites. Each site can obviously handle many more patients. That is the promise of short-duration psychedelics. That is why we've been focusing on it. All right. With that, I'm actually going to just pause there. Athena, you know, happy to take any questions.
I do have a question actually about all the different short-duration psychedelics in development. Who do you think would be the ideal patient for something like BPL-003 versus Compass's COMP360, which is about six to eight hours for treatment?
Yeah, I mean, I think the short answer is it's going to depend. One of the things that I mentioned is we don't have a good sense of durability of response with the short-acting compounds, right? I mean, we anticipate some difference potentially between BPL-003 and VLS-01. With DMT, there are two short duration studies that were conducted. One was only a week. It was actually using ayahuasca, and ayahuasca, the active moiety, or psychedelic moiety there is DMT. Another one was an IV infusion of DMT, very short infusion. The first trial went out to a week, as I mentioned.
The second only went out to two weeks, at least in a double-blind context. They had good separation. 5-MeO-DMT, believe it or not, does not have double-blind placebo-controlled data beyond a week. In fact, that one-week data was just recently released by GH Research. That is it. That is all we have got.
Are there any learnings you can take away from that study design that you might apply to any future study designs that you are in the works about?
I think that that trial design is likely to be problematic. I mean, it was a, you know, one of the things with psychedelics, of course, is their dysfunctional blinding of the patient, right? Not a big deal. Most, you know, CNS drugs do have a degree of functional blinding. That is not a problem.
What you want to see is a dose response, and you want to see durability. If you go back to Compass's phase II- B trial, they showed both of those really quite nicely. They looked at one milligram, 10 milligram, and 25 milligrams. They showed that 25 milligrams clearly separated from one, 10 did not. Nonetheless, 10 milligrams had good psychedelic effects. It suggested that it was not just a psychedelic effect. There is something above and beyond. That was a good demonstration. They had durability out to 12 weeks. All of the other programs, to the best of my knowledge, if you look at the trials, they all resemble that trial. In fact, our trial does, you know, VLS-01, BPL-003, all kind of resemble the Compass phase II- B trial.
I mean, there's subtle tweaks to them, but that's kind of the general thing. I don't know where to take that with the GH Research. I'm curious to see where it nets out with the agency. My hunch is that they'll have to do something that's more traditional that looks more like some of the other trials. We'll see.
You mentioned that you are currently designing or thinking about phase III program design for your TRD programs, correct?
I mean, sure. We're having some top-level discussions, but ultimately that's going to get guided by the data that we see, right? In the case of BPL-003, there's the core eight weeks of blinded durability. Then there's an open label section that gives you one dose, and then there's another eight weeks of assessments. With VLS-01, we have two doses.
We wanted to actually assess what the impact of a second dose would be. We have a four-week primary, then we have 12 weeks of blinded durability, then open label redosing with one or two doses. They're blinded on which dose they get, and then a subsequent two doses. We need those data to really understand redosing, et cetera.
Your target dosing annually would depend on that durability that you see from these phase II-B studies.
Yeah. I think, you know, again, it's if you think about Spravato, it's induction and maintenance. Induction, as I mentioned, is up to 12, it's 12 doses per label in eight weeks. Then it's every week or every two weeks, but really going with the minimum amount. It could be less than that for a given patient.
To maintain remission, it's kind of at the doctor's discretion. Some people get it once a month. Other people do indeed get it once a week. We anticipate it being much less frequent with any of these psychedelic compounds.
Is there an effect size that you are targeting for your phase II-B, BPL-003 study?
Yeah, I mean, we haven't got it publicly on effect size for either one of those. But, you know, if you think big picture, the delta, the MADRS change delta with Spravato was four points, right? It's an efficacious drug. It's a good proxy. You know, we want something at least as good, if not better, but obviously with many fewer administrations. I mean, I think that's an important point of differentiation here and presumably more durability beyond it as well.
I think recently we've seen a lot of rising placebo responses in depression trials from other sponsors. What are you doing to try and mitigate those effects? Can you speak to kind of what is driving that response?
Yeah, that's been a perpetual discussion in psychiatry. I mean, it's a tough one to answer. You know, there's some trial, you know, the trial designs that you can think about that certainly increase placebo response. I mean, the closer you get to 50-50 drug versus placebo, the better. In the VLS-01 study, that was one of the reasons the core study is actually just either placebo or an active arm. That kind of minimizes things. You know, trying to minimize the number of interactions, having a lot of therapy, blah, blah, blah, is going to increase your placebo response.
Having a lot of putting on laying your hands on the patient a lot is going to increase it. Certainly with VLS-01, there's very limited interactions with the site for exactly that reason.
How limited?
In the case of VLS-01, we have a prep session, if you will, which is really giving the patient informed, much more informed consent, essentially, because it is a very unusual experience. You want to make sure the patient's prepared. That's one hour. Then there's a subsequent visit after the fact, and that can be telehealth as well. That's also an hour. It's just to assess psychological safety. Sometimes things do come up during these psychedelic effects, you know, past traumas, et cetera, can come up, and you just want to make sure that the patient's obviously taken care of in that context.
Are you capping prior users in any of these studies?
Yeah, with the VLS-01, it's up to two uses of a compound in lifetime and nothing in the past six months.
Understood. Let's move on to RL-007. Your data readout for cognitive impairment associated with schizophrenia are anticipated in the middle of this year. What can we expect from this top-line readout? Will it feature primary and secondary endpoints? What are the key secondary endpoints that support your primary analysis?
Yeah, I mean, the primary is actually the regulatory endpoint. It's the so-called MCCB, the MATRICS Consensus Cognitive Battery. That's what we're focused on. That is seven different domains, I believe. Yeah, seven different domains. We're not looking at the social cognition bit, but we're focused on the other ones. That is what everybody has used, and that is what the FDA basically expects.
It is a difficult endpoint because of all of those domains. There's a total of 10 different, you know, 10 different instruments that are used to, you know, to create those different domains on the overall score. We are looking as key secondaries at some of the subscores. In a small phase II- A trial that we ran that was essentially open label, but there was a blinded section kind of in between, the patient was started on placebo and then transitioned to drug, and they didn't really know when. In that context, we had, you know, we looked at sort of subscores within the MCCB. Symbol coding is a very nice proxy for cognition writ large. It has good correlation with the MCCB. It's a very simple and objective test. That's going to be a key secondary endpoint that we're going to be looking at.
There's also functional endpoints, which are something the FDA ultimately wants to see. We don't anticipate that moving markedly over the course of six weeks, but of course, we are collecting that data.
You mentioned 10 instruments as part of the MCCB. What does a patient need to show in order to move that scale by a point?
It's usually measured in T scores. Essentially, everything has been normed literally to a normal population. It's not each, and I don't think it's each individual instrument for the purposes of scoring, but it's at least groups of instruments. You're trying to, you know, typically, you know, if you look at cognition, if you look at IQ, folks with schizophrenia tend to be at least one and a half, but typically closer to two standard deviations below where they should be.
You want to see kind of improvement on that, of course, from baseline. That may not be across all different domains. That is IQ. You might see, you know, you want to see getting closer to normal, at least moving, you know, half standard deviation, but standard deviation essentially would be fantastic.
Understood.
I mean, big picture, where do I see this ultimately being deployed is, you know, there is cognitive remediation therapy that is useful for patients with schizophrenia. It really helps because they have so much executive dysfunction. It really helps them, you know, be able to plan things, just activities of daily living. How do you prepare to go to a store to pick up your groceries? Seems pretty obvious, but it can be difficult if you have executive dysfunction. You know, cognitive remediation helps with that.
If you've got a compound that makes the patient more receptive and more capable while they're getting that, I think you're going to potentially get more benefit. That is where I really see the big benefit from compounds like this coming from.
Are there any safety signals of note from this compound that might differentiate from what is available as standard of care?
Standard of care is really atypical antipsychotics and, you know, some typical antipsychotics as well. They are, you know, very well described. They work well for positive symptoms. They don't really work for negative symptoms. They don't really work for cognition. I mean, there's some small exceptions. Clozapine may have a pro-cognitive effect. We, you know, certainly that was hinted at, but generally there's not a huge benefit. This is going to be an adjunct of therapy.
The interesting thing about this drug is that despite the fact that it seems to have a GABA-mediated, you know, effect, GABA agonists or positive allosteric modulators tend to be sedating. This is not sedating. Overall, it seems to be very well tolerated, even at high doses. The pro-cognitive effects tend to go away when you're at very high doses, but it still remains quite tolerable.
Understood. Before I hog all the questions, did you want to go through any more slides?
No, those were it. I, you know, yeah, within this particular deck.
Understood. Are there any audience questions? Yep.
What do you think new market research, were there other factors that patients cited as reasons for wanting another therapy?
I think it was.
Sorry, let me just repeat the question to make sure I got it. On the BPL-003 program, was there any market research that.
That's it. Yeah.
Frequency of dosing and, you know, obviously efficacy, I mean, this is one of the things you got to think about with depression is it's a very heterogeneous condition, right? There's this final common pathway that is depressed mood. And if you look at the DSM-5 criteria for depression, you can have patients that look completely different that meet the criteria that are both diagnosed with depression. I mean, you can have one that is hypersomnolent, is sleeping all the time, not really doing anything. And you can have another person's bouncing off the walls. And they both meet the criteria. You know, having some additional pharmacological choices that are differentiated, I think will be another important one. Certainly patient convenience is going to, is kind of front and center.
Having something that's more durable is really important. Ketamine, esketamine, you know, again, for each individual administration, it tends to be short duration, short-lived to benefit. People feel pretty good the day of and the next day, but it, you know, progresses pretty quickly back to baseline. You do that multiple times and you seem to drive them into remission, but it just, you know, it isn't, and it does take a number of administrations to really know that you're going to be on a good trajectory. With these compounds, we anticipate with a single administration, you got a pretty good idea whether or not the patient's going to benefit. Kind of a new paradigm really for this space.
Yep.
You're studying EMP-01 for a social anxiety disorder. Can you please tell us about the market and how it compares to generalized anxiety disorder? What potential endpoints were used for this indication? Would something like AMA still work?
Question was on EMP-01 and what the market for social anxiety disorder is and how it compares to generalized anxiety disorder and what are potential endpoints that could be used for an SAD study.
Yeah. Perfect. Yes, SAD is a pretty large, is a large indication. In fact, it is substantially larger than depression. It is more, it is quite impactful. It is just one of those things that sort of languished for a long time. There are three approvals for social anxiety disorder in the United States: two SSRIs and venlafaxine, which is an SNRI. The last one is in 2003. There obviously is a regulatory endpoint. It is called the LSAS or the Liebowitz Social Anxiety Scale. That is what you would use. In terms of size comparison, the GAD, I think it is generally comparable.
GAD is considered a bit larger. There are more medications that are used for GAD. I mean, certainly SSRIs, there are also approved compounds there. In terms of SAD, the SSRIs are not great. The primary, you know, mode of therapy at the moment is cognitive behavioral therapy. It works. It works great for depression as well. It's just that it's difficult to deploy and, you know, it's time-consuming. Most people don't do very well with it. If you're in a very controlled setting, sure, CBT works great for a lot of different things. The interesting thing about social anxiety disorder is, of course, everybody knew it was there and knew it's been, you know, that it's impactful. It really has risen to the fore after COVID, right? All that social isolation made it much more problematic.
You know, the kids that were in high school are going to be stuck with this for a while. It's funny, my youngest described herself, and she was, I think, I mean, she's a sophomore now. She was in middle school then when COVID started, obviously. She describes herself as an extrovert with social anxiety disorder, which is kind of funny. It is true. I mean, that's literally what we're talking about here. You know, the two can coexist. It is kind of where depression was probably 10 years ago or treatment-resistant depression, certainly. Maybe people sort of thought, talked about it, but it wasn't really considered, you know, it wasn't a focus. There are a couple of companies that are looking at compounds for PRN use, for as-needed use. If you're going out to a party or something, you can take it.
Vistagen being one of the examples there, Bionomics, they changed their name, but they have another compound. It's the same basic idea. They're using a different endpoint. It's subject to units of distress. So you basically ask them how intense it is. They do that in a provoked study. It's a simulated public speaking context, but that's different. Ours is a much more general, presumably much more general. And so we're using the Liebowitz.
Have you conducted any abuse liability studies yet on EMP-01, or do you plan to?
I think in general for all of these, you'll end up doing them at some point. In some cases, things have been done, but the pharmacokinetics for all these compounds is going to be different. We will, again, we will end up doing it at some point.
It's interesting that the reason we went after R-MDMA is that the pharmacology of the two enantiomers is so different. S-MDMA has dopaminergic, and norepinephrine kind of effects. And the R enantiomer has a much more serotonergic profile. So our conjecture going into it was, and so the S is really much more like a stimulant. That's likely where the bulk of your abuse liability is going to come from, just based on other drugs. The initial premise was that you're going to get a compound that has a much better safety profile, cardiovascular safety. I mean, MDMA itself causes hyperthermia, which is not great. You've got, when you're thinking about PTSD and in particular, you do have increased prevalence of cardiovascular risk factors. You know, we wanted a safer drug.
When we actually tested it in phase I, we did get a better profile. Blood pressure and pulse were better, but it just looked so different. It had these weird elements of a psychedelic compound combined with an antagonistic compound, but it didn't look like most psychedelics. For example, you know, we compared it to other publications around MDMA as well as with psilocybin. You know, there's the, in the 5D-ASC, it's commonly used. One of those, you know, there's oceanic balance, but there's also this visionary restructuralization, which can be just about hallucinations and things like that. In this case, the normal healthy volunteers were saying they were able to view their life differently. That's just a different level of abstraction, right, than what we think about with a more traditional psychedelic like DMT, 5-MeO-DMT, psilocybin. Very interesting profile.
I love it when there's an effect I didn't expect, right? That's one of the reasons we're like, we got to go do something with this and take it, you know, take it to the next level.
Very exciting. In the last 15 seconds, do you have a favorite program from your pipeline?
Everybody asked me that. No, I don't have a favorite. No. I mean, I'm pretty, you know, VLS-01 has been my baby for a long time. Wow. Yeah. You know, we started with this a couple of years ago and really kind of focused on this very cool formulation technology, which turned out to be very difficult to implement. It's just complex. Got a fantastic profile now, really good pharmacokinetics, incredibly good bioavailability. Pretty excited about that. Again, as I mentioned, EMP-01, different than anticipated. That's always exciting. I love BPL-003 and RL-007.
RL-007 was my PhD work was actually focused on cognitive impairment and schizophrenia. I think they're all a little bit different.
Absolutely. Thank you, Srini. We are at time, but thank you all for joining us today and hope you enjoy the rest of the conference.
Thanks.