Okay, so we're going to get started with our next session. I'm Andrew Tai, Senior Biotech Analyst at Jefferies. Thanks for tuning in. It's my pleasure to have the Atai team with me. To my direct left, Srinivas Rao, CEO, and to his left, Christian Angermayer, co-founder of Atai. Welcome, both of you.
Thank you very much. Thanks for having us.
Thanks. Maybe to start, help us frame the Atai strategy briefly, what you're trying to achieve and how you're differentiated from other psychedelics.
Yeah, a couple of elements to that. We obviously have been in a company that's been in a bit of transition, right? When Atai was founded, it was much more of a hub-and-spoke type organization. We had a range of investments, essentially. Some of those were partial investments. We had investments in public companies, et cetera. The assets that were developed were really being developed under subsidiaries for the most part. Some of those are wholly owned. Now, we've been simplifying that tremendously. Many of these assets sort of died organically. We had pretty high bars for advancement. Now we have, with this recent announcement with Beckley in particular, a more traditional pipeline. It's three assets that are in clinical stage and phase ll that are psychedelic in nature, that are wholly owned.
We do still have some legacy from the previous model, which is Recognify, that's developing a drug for cognitive impairment and schizophrenia. We own approximately just under 60% of that company. That's in a slightly different space. I mean, we had a somewhat broader mandate initially around both psychedelic and non-psychedelic compounds. We are really kind of focusing it down on psychedelics. In that context, we have the points of differentiation, particularly for the lead compounds that are in depression, is that we have always looked for compounds and drug products that will cleanly fit into the Spravato paradigm. We want that to be a single administration, just like Spravato, hang out in the doctor's office, just like Spravato, get assessed, and go home. Keeping it simple, but hopefully getting better degrees of efficacy, but also, equally importantly, many fewer administrations.
That's going to be the important element.
Great. Do we want to start with some questions for Christian? Big picture?
No, let's go.
Why don't we just walk through the stuff and then, yeah.
Sounds good. Sounds good. Okay, so congratulations on the Beckley deal.
Thank you.
That's great. I mean, you have essentially potentially whole ownership of that compound. We have a data set coming up in mid-2025. There is also actually another compound that you have for CIAS, the Recognify Acid, also due mid-2025. Can you give us the cadence of catalyst? Which one comes first?
I mean, we haven't really publicly guided that. They're sort of on top of each other, and they're both relatively forthcoming. They're going to be in the not-too-distant future.
Okay. Okay.
I don't know if everybody knows the sort of Beckley deal you referred to, because this week we had, so we always had, always since January last year, we had 35% in a company called Beckley Psytech, whose lead compound is 5-MeO-DMT. That was one of the examples Rao said. In the past, we were more flexible, having minorities, majorities up to 100%. We decided two years ago to more like sort of clean it up, be like more like a traditional biotech company with fully owned compounds. The question most investors always had over the last two years, what's going to happen with Beckley? Because it's a super interesting asset, which is reading out late this year.
What we did, which I hopefully, I think people liked it a lot, because I think we're also good dealmakers, we signed a takeover of Beckley versus shares for 100% of the company. For the remaining 65% we didn't own yet. However, closing is just if the phase ll-B data is meeting certain, from my personal point of view, very stringent, high-up bars of efficacy and safety. If not, we could walk away. It's practically, and we're all in finance, a free option, which I think you always take.
Yeah.
We do expect, obviously, the data will be very good. That's why we wanted to sign now, so that on the day you read the data, you also know.
Hit the ground running.
Okay, we are the full owner of Beckley. It is very downside protected for Atai and our shareholders.
If I were to ask back the Beckley team, I mean, they're joining our team, it seems like, by then.
Yes.
Why did they take the deal? What would they say?
I mean, there's.
Very convincing.
Yeah, no, I mean, there's clear conviction in the asset. I mean, we all have expectations on that trial. The efficacy bar is stat-sig on the primary. I think that given the nature of the study, given the nature of some previous results that admittedly were open label, there's a lot of comfort in that. More fundamentally, I think there is, again, it's a clear recognition that being separate at that time could mean that there's going to be some efforts that are at cross purposes. By aligning this way, we're moving in lockstep to get the next trial going, to get things funded, et cetera.
Makes sense. For the top-line release, what can we expect to see in terms of efficacy, safety? Are you going to share kinetics? Are you going to host a conference call? Just level set expectations here.
Yeah, of course. It depends on results, of course. Pending positive results, it will be the so-called core study. What that means is the four-week endpoint. We have a total of eight weeks of blinded follow-up. It is four-week primary and then four weeks of additional data. It will be that core study looking at efficacy, obviously the MADRS, responder rates, et cetera, as well as safety. It will be a pretty robust data set that we will be presenting. That is the plan. Yes, we do anticipate having may i call it , to kind of walk through it at all.
How did you power this study? What did you power it to show on the four-week primary endpoint?
I mean, we haven't really guided the details of the powering assumptions, but I think you can look at the size of the trial and kind of back out. I mean, it's not that, so what are the data sets that would go into it, right? This trial was heavily based upon the Compass trial, right? The Compass phase ll trial that read out a few years ago. It's essentially the same design as that. Data, I mean, you know what the variance and other things there are. I think that's a reasonable place to anchor.
Is the threshold that you've established with Beckley the same threshold or a similar threshold for this study, or is it a higher threshold?
Oh, I see where you're headed. No, it's stat sig on the primary.
Okay.
Yeah.
I mean, but ultimately, to get a drug approved in TRD, we're talking about a two-point separation versus placebo.
Yes, two to three points would be the lower bar. The way to think about that is you can get that with a huge trial. Like if I had 300, if I had 500 patients per arm, you can start discerning ever smaller separations. Considering the size of the trial, you're not going to get there. It can't be too small because there is sort of a floor of variance. It's not like the variance is going to be markedly, markedly, markedly better than other trials, TRD trials. You can't get there. You can't get down that low and still be stat sig. It's kind of the long and short of it.
Of course. Yeah. It is an eight-week-long trial, but a four-week primary. Would you expect curves to widen? There are two active doses versus a low-dose inactive dose. Do you expect curves to widen over time versus placebo out to week eight?
Certainly the open label data that we have suggests that it's very flat. In other words, the response curves were single administration out to three months in those cases across 23 patients at this point. You got good response, and it sort of stayed there. Traditionally, with placebo in single administration trials like this, you'd anticipate the curve to kind of go back to baseline. That would be great. I mean, the reality is that this is the first real robust data set for a short-duration psychedelic, right? That gives you a primary endpoint that is regulatory in nature, right? Four weeks to six weeks is a regulatory sort of time frame. It also gives you that blinded durability data that we really need to assess.
I know where you're going, like how does this, these data are going to be critical for designing the phase lll program, as an example. Yeah, this is the first real data set that will be generated for that.
Right. Ultimately, what kind of dosing paradigm in terms of number of redosing do you, what's your base case expectation for this compound?
I mean, again, haven't really guided on that. We're looking at a single administration in this trial, understanding the decay curves with this. In the VLS-01 phase ll trial, we're doing two doses, very much anchoring on induction and maintenance as a general concept. If you look at the label for Spravato, it's literally that. It's induction. In the label, it's eight weeks. It's 12 administrations over that time. Maintenance is after that. For Spravato, it's 12 administrations in eight weeks. After that, it's every two weeks. There was a recent poster that was presented at ASCP, I think it was last week, that showed that 60% of patients that are on Spravato are taking it every week from there on out. They're against the label in a sense, but taking it very frequently.
What we're expecting is something like one or two doses for induction over four weeks. Maybe if it's six weeks, it could be another dose. And then a paradigm that's closer to once every three months after that. Of course, we need the data to be definitive on that.
Of course. So would you expect a dose response between the two higher doses?
I mean, it's possible. We'll see. I mean, there's less separation. Compass was kind of the poster child here, right? They looked at one, 10, and 25 milligrams. Here we're looking at 0.3, eight, and 12. The difference between eight and 12 is obviously less than what Compass did with 10 and 25.
Probably more overlap.
Yeah. Remind us, you mentioned the open-label prior data just to level set or remind the people listening, what kind of MADRS score reductions did you see in the open-label monotherapy as well as adjunctive trials? What kind of reaction rates?
There are two cohorts there. It is a phase ll-A that had multiple cohorts. The first cohort was monotherapy. There were 12 patients dosed, 11 evaluable. The second one that was just recently announced was SSRI. In other words, adding on to SSRI. I know the first one was around 15-16. It could have been a little bit higher in terms of the separation of the delta from baseline. I do not remember if that data was actually presented for or made public for the second bit. I mean, a lot of that, the change you see is heavily dependent upon the baseline. These are around 30-ish, just under 30. That is a pretty robust separation or reduction.
Right. Would this phase ll-B data set be considered a potentially pivotal study?
Gotten that question a few times. There's certainly scenarios where, let's go to Spravato again, right? Spravato for acute administration did rely on some phase ll data because some of their trials were negative, right? Transform two was their so-called, it was basically their induction trial. They used that. They used some of the long-term data. They used some phase ll data. Phase ll data can always be supportive, particularly if one of the phase lll's does not hit a 0.05. There's nothing special about that. If it hits 0.10, 0.10, but you have good supportive data from the phase ll, certainly you could go down that road. There's certainly been discussions around how the current administration may look to accelerate things. There's been discussions about going to a single trial. In that context, a phase ll could be considered pivotal.
Would that change how you approach the phase lll program? That's a different question. Again, we know that so far, the psychedelic trials have been robust in terms of the efficacy that's been demonstrated. Depression trials do fail because they just fail. It just happens. There's a long history of this. Would you go after a single trial only? Because if that, for whatever reason, something happens in that trial, you are now behind by three years. Usually you try to do at least one additional trial. Like in a previous program that I was at a company where I was Chief Medical Officer, we needed two trials, two pivotal trials. We ended up doing three, initiating three trials to get those two. It just doesn't cost, it costs you too much time and too much money if you don't do it that way.
Right. And for this class of drug, 5-MeO-DMT, there's another company, GH, which reported positive data already earlier this year in their own phase ll study. Can you kind of give us a compare and contrast your drug as well as your study design versus GH? Why do you think your program is ultimately more robust than GH?
There are very different routes of administration. GH Research is using a vaporization technology and then pulmonary absorption. Very, very rapid decay. It gets into the system very quickly. If you think about it, the absorptive area in your lung is about a football field. The BPL asset is using intranasal transmucosal. That just goes, kind of sticks to the inside of your nasal cavity and gets absorbed. That is a few square centimeters. That is the difference. Pulmonary, again, vaporized, kind of crashes out when it hits the colder lung parenchyma, goes in very quickly. Cmax, I mean, Tmax is usually tens of seconds. Cmax can be very, very high. Bioavailability tends to be very, very high. Transmucosal, the Tmax is around 15 minutes or so. It varied a little bit with dose. Certainly a bit kinder and gentler.
Because of that, it also takes longer, which is what we were going for. We wanted a psychedelic experience that maximized that sort of two-hour window that Spravato has set. That is the first bit, just route of administration. I have worked previously with other companies that did pulmonary. The FDA does not like pulmonary administration or they are very particular about it. They want to make sure there is lung safety. There are a lot of requirements put in place. Indeed, GH Research is currently on a clinical hold, I think mainly pending some lung toxicity data, but I do not know if there are other elements there. The technology that we are using with BPL-003 is off the shelf. It is a dry powder Aptar pump, essentially. The technology that GH is using is more ad hoc. It is not something that is completely novel, right?
It's essentially, it's called, it's based on something called a volcano. Essentially, there's a balloon, there's temperature, I mean, there's air that's kind of blown across the drug. It just blows up the balloon, then that's taken off and then it's inhaled. I think, I mean, that's fundamentally what we've surmised based on what we've seen. Just different. The FDA usually when something is new requires more data around that technology. We're doing Spravato paradigm. You come in, you get dosed, you get monitored, and you go home. GH Research is using IDR, the so-called IDR, independent individual dose response. They start with a low dose. The patient's administered that. They're asked essentially the intensity of that experience. If it wasn't a full psychedelic experience, they're redosed on the top of the next hour. That pattern can go one more time.
I think it's six, 12, and 18 milligrams is the sequence. Now, that can, it's more variable on its time. I mean, you could certainly see scenarios where it pushes up against more than three hours, assuming that the redose doesn't occur exactly on the clock, right? In terms of the trial, there's two elements that are markedly different. The first is blinded data, right? We are following the patients out in a blinded fashion for eight weeks. That is to understand functional and blinding elements, right? To really see if there's all placebo response, everything should decay back relatively on the same curves. We're also doing dose ranging. In the context of GH, it was no dose ranging. It was this IDR paradigm. It was also only an eight-day primary. Eight-day primary and then no blinded follow-up afterwards.
I think that's kind of challenging. It makes interpretation very challenging. I think that's what I and other people have kind of struggled with there.
Is your study global or U.S.?
It is global. So it's parts of Europe, U.S., and Australia.
By extension, you've spoken to the FDA about this trial design.
Oh, it's a good point. No, this compound, BPL-003, I think the R&D was in October. No, it was in March or April of 2023. So it's been under R&D for quite some time.
Got it. And so since GH is on clinical hold, your argument presumably would you can leapfrog them ultimately?
I mean, potentially, yeah. I mean, it depends on how they approach it, of course. We have no insight on that. It makes sense to clear the clinical hold before having an end of phase ll meeting, generally speaking. That does not mean it has to happen that way, but it certainly simplifies the discussion.
On the patent side, what are the differences between you and their?
Beckley has issued US patents around the salt. And it's a robust patent. We've obviously done a lot of diligence on that. You can't do a salt switch when you want to go, when you want to use NANDA, right? That's a really important point. It's actually a pretty robust patent around that. There's additional patents, one of which is issued around formulation. There are many other patents that are pending. GH Research does not have any U.S.-issued patents. There are some broad claims that were issued in Europe. The patent process in Europe is very different than the United States. In the U.S., there's no opposition period. There's presumption of validity immediately upon allowance. In Europe, there is an opposition period. They are allowed, and then there's the potential for pushback. The validity is validated through that process.
There have been oppositions that have been filed against the European claims. Then there's also been some office actions here on the GH Research patent. Very recently, actually, like two weekends ago, that was robust.
Okay. Does your trial employ psychotherapy?
No.
It's psychological support in both cases. What that means is really prepping the patient. For someone that's not taken a psychedelic, that is naive to psychedelic, it is a very unusual experience. It can be an unsettling experience. Making sure that the patients are adequately prepared for that. Just giving them some skills like, how do you settle down if things are getting too intense? You can just do some deep breathing, etc. That sort of stuff is provided upfront. Afterwards, it's basically around assessing psychological safety. One of the things that can happen with these drugs is things that happened in your past can reemerge, can become evident to you. Trauma of some kind can kind of surface. You obviously want to make sure that that person is being followed up with psychological support or a psychologist very quickly.
Understood. The patients who are enrolled in this study, what percentage of them do you have prior psychedelic experience?
We're being pretty aggressive in both trials to make sure that it's low, right? In the COMPASS phase ll, about 6% or so, I believe, had prior use or prior history of using a psychedelic. We are looking at at least six months of no psychedelic use and no therapeutic psychedelic use. In the case of VLS-01, it's only two lifetimes. The target is sort of single digits, certainly.
Understood. And so next steps, should this phase ll be positive in stats, the acquisition would close, then you meet with the FDA or maybe in parallel?
No, we do this in parallel. We don't want to waste any time, as we said.
The heart of the question would be, when is the earliest you can start phase lll?
I mean, we haven't really guided on that because we need to see the data. We need to have the discussion with the FDA. I mean, if everything goes well, I mean, it would be, obviously, it'd be next year, but not guiding any more clearly than that.
Okay. Okay. We'll stay tuned for the data readout. Christian, maybe some questions for you. I mean, since you're here, what are, you've been dealing with psychedelics for quite some time now. I guess the big picture question would be, what are one or two things you think investors just don't, what are the misconceptions basically amongst the investor community?
I think mostly around commercial. A little bit the funny fact is like to most investors I talk, I would say at least half of them are like, "Look, I've done it in a country where it's legal like me. I know this stuff works. I know it's safe. I believe it's going to get approved." They look at Spravato, which is the most comparable, although it's not a psychedelic, but psychedelic-like, and see that Spravato had a slow start and say, "Okay, this is going to happen to you as well." By the way, the same is true for Pharma, who also looks at Spravato and thinks, "Okay, we're going to have more time to act on whatever acquisitions, partnerships." I think that is fundamentally wrong because A, Spravato started in COVID, was just a very different time.
B, it was also a different time in society. It was the first, SIMI or whatever you call it, psychedelic-like. And I know that some of the J&J folks really well, they did not know really what to do with it. The rollout was kind of clunky. Then the therapists needed to educate it. They needed to sort of change their workflows in their clinics, whatever. It was a combination of COVID, some homegrown facts at J&J, but also the fact that it was the first of its kind. Now, some years later, when all of these problems have been overcome, you see how crazily Spravato is growing. I personally think it has a way to go in terms of revenues. I think investors do not make that sort of, "Okay, we are not going to do the six-year slow rollout.
We're going to jump. That is also what we at Atai, as Runi said before, are focusing on. Yeah, we're focusing on exactly that two-hour window, which people know now. Patients know it. Therapists know it. Clinics know it. It will be a much more quicker rollout than people think.
When you say the two-hour window, can patients even drive home, technically speaking? I guess the investor question would be, what difference does it make in the sense they're not going to work that day or something like that?
We have Uber in the meantime.
Yeah. I mean, I would be a little reticent for folks driving home. Of course, that would not be where one would start. You would do the driving test. You'd be pretty robust on that. I mean, at some point after the fact, I mean, these drugs do get cleared very quickly. They have about a 10-15 minute half-life. The usual rule is five half-lives. I mean, within a couple of hours, you're way past that. There's really nothing kicking around. That potential exists, but certainly you're not going to start there. The fundamental thing is each day with Spravato is not that bad. There's just so many of them, right? You could certainly, by making it shorter, making it less frequent, rather, you're certainly simplifying things.
In terms of the, from the provider perspective, the challenge with longer compounds is if we'll step back. I mean, the standard day is usually around eight hours, right? That's the first thing. Then some patients will require longer, right? Something happens, they get anxious, their blood pressure is elevated. It happens with Spravato, right? Those folks are not getting discharged in two hours when it's Spravato. They may not be getting discharged immediately then with psilocybin either. You do not have a lot of headroom with something like psilocybin. You would with a short-duration compound, right?
It's a cushion or something.
What's that?
A cushion.
Yeah, you have a bit of a cushion. Doctors were happy with the ability to have more than one patient in a day. I mean, that was something else that came up as opposed to a single one.
Okay. Going back to Christian, it seems like you're close to Trump and the administration. I mean, what are you seeing where this administration will go?
Realizing biotech, it's not a badge of honor, but yes, I have some businesses with him and his family. I mean, in general, I think what is always our important point, the FDA has been always very supportive for psychedelics. I think it was a little bit distorted in the perception because Lykos, we're not going to go there, but with all of their own problems, they tried to turn it around and blame it on the FDA. I think that gave some of the investors the feeling as if the FDA is not supportive, and they completely are all the time. However, it does help additionally. Again, FDA is just continuing to be supportive, but it does help that we have an administration where key people like R. F.K. or Sir Macquarie are outspokenly positive on psychedelics.
What I think they will do for the anti-industry, and obviously we're talking to them because we're close, how I see that unfolding for psychedelics, but neuroscience in general, is what can be cut down in sort of a reasonable way. I think, for example, if you look at psychedelics, there might be reasons, but I think, do we really need two phase lll's? Obviously now is the, well, as Runi said, you don't want to take one phase lll if you don't know if that is enough. Let's say hypothetically speaking, if they would say the next month that just one phase lll is enough, full stop, again, obviously provided.
That's different. Yeah.
That would make a huge difference for psychedelics companies. My personal view is that's where they might want to go.
Makes sense. Maybe one more question, last question for you, Christian, is you started another company, the Enhanced Games. It's a sporting event where my understanding is doping is not just allowed, but endorsed.
Yes. We do not call it doping then because doping is a negative word. No, it is like, but performance-enhancing drugs. It is called Enhanced Games. It is going to be in Las Vegas next year, Memorial Day weekend. By the way, with very positive support from R.F.K., Trump's president, who is going to open it. We allow performance-enhancing drugs because the IOC did a fabulous job pretending doping is illegal, which it is not. It is banned, meaning you sign a contract as an athlete that you are not using performance-enhancing drugs. By the way, 25% of all drugs on the World Anti-Doping Agency list are available at your GNC next door. You sign that in a contract. Yes. That is why it is cheating if you do it secretly. In our event, we do not have that. We allow all medical products.
Why this maybe has a relationship also to psychedelics, I think one on a very high level. That's not going to happen this year, but one development where the key people in healthcare and this administration are focused on, who are the key people, like R.F.K., obviously, but I would tell everybody pay even more attention to a very good friend of mine, Jim O'Neill. He got confirmed yesterday. He was in biotech before. We worked together because he was working for Peter Thiel. Peter Thiel is obviously very influential. What is really what we all hope sort of which is going to get done in the next four years is a redefinition of actually what is an illness and what is medicine. Because we have, and I had this in the briefing before this talk, I was like, "Don't talk about off-label use." Yeah.
I'm not going to talk about off-label use as the Chairman of Atai. Yeah. But it's a bizarre situation that we have a whole industry, and I think we all should be much more, investors, CEOs alike, where we're just defining a very narrow, and by the way, for some drugs, it makes sense. Obviously, you just need oncology if you have cancer. Yeah. There are other drugs where the definition of illness is a very subjective one. Yeah. For example, if you take obesity, yes, we have medical definitions of obesity, but there might be people who say, "Look, I feel not happy with my body as it is," and now they're taking Ozempic. Ozempic, the biggest driver by far is what we unfortunately still call off-label use.
We should, so one big push we have a group of people is doing with the current administration is to redefine that and to allow for certain topics, humans define what you want to be. By the way, in a very crazy way, the last government did that because we had the whole transgender movement. Transgender is one of the crazier, I mean it positive, crazier extreme ways where people say, "I am born as a man and I want to be a woman." By the way, it's fine. I'm very libertarian. If we allow that group of people to take very heavy drugs, I mean, that's real heavy stuff. Why would we not allow somebody who says, "Oh, I want to be slimmer," yeah, very officially a prescribable weight loss drug?
Why don't we allow somebody who says, "I want to be checked and ripped," some anabolic steroids? Yeah. Why don't we allow a person coming through psychedelics who says, "I'm not depressive, but I could be happier. I'm going to a bad phase in my life." Why don't we proactively allow those people support? Yeah. I think that will be the biggest change if we get that done in the current administration. I think that's going to tremendously increase the addressable market for certain biotech companies.
Okay. I got to end it here, but thank you for sharing these insights. You're clearly pioneering the space a little bit. Thank you, everyone, for tuning in and thanks for coming.
Thanks.