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TD Cowen 46th Annual Health Care Conference

Mar 4, 2026

Rituparna Roy
Senior Analyst, TD Cowen

Okay. We are gonna go ahead and get started. Thank you everyone for hanging in there, in the final afternoon or close to afternoon, of the third day of the 46th Annual TD Cowen Healthcare Conference. This is the Fireside Chat with AtaiBeckley. I am Rituparna Roy, senior analyst, covering analyst for Atai. With us we have Srini Rao, CEO and co-founder of Atai. Srini, thanks for joining us.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Thank you for inviting me.

Rituparna Roy
Senior Analyst, TD Cowen

Let's start with your lead compound, BPL-003, a candidate that you got, when, with your business combination.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah

Rituparna Roy
Senior Analyst, TD Cowen

... with Beckley, after their quite impressive early phase II data, in TRD. This is intranasal 5-MeO-DMT.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Okay.

Rituparna Roy
Senior Analyst, TD Cowen

A key differentiator 'cause there's no sort of intra therapeutic regimen titration.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Correct. Correct.

Rituparna Roy
Senior Analyst, TD Cowen

It's one dose. Yesterday you announced your phase III pivotal TRD design following your positive End-of-Phase II meeting with FDA. Can you describe the two phase III designs and how they incorporate FDA feedback? They do differ a little bit from.

Srini Rao
Co-Founder and CEO, AtaiBeckley

They do.

Rituparna Roy
Senior Analyst, TD Cowen

written guidance from, like, a couple years ago.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah. Yeah, absolutely. I mean, basically we have these two phase III trials. The first one is 350 patients. It's looking at the go forward dose, the dose that was demonstrated to be effective in the phase IIb of 8 milligrams. Looking at an intermediate dose that is, has a psychedelic effect, but substantially less than the 8 milligram dose, that's 4 milligrams. Looking at placebo. It's a four-week endpoint.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Primary endpoint, it's 12 weeks of blinded data. There's an open label extension beyond that, so nominal redosing frequency is every 12 weeks. Because this is such a short duration compound-

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

We thought it would be beneficial to also allow redosing if the patient requires it as early as eight weeks, so a little bit more frequent if necessary.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm. Why four weeks versus the, like, three weeks that we've seen with psilocybin?

Srini Rao
Co-Founder and CEO, AtaiBeckley

It's an interesting question. Most of the other psychedelic companies have focus on a six week primary endpoint.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

We didn't have a very good explanation as to why.

Rituparna Roy
Senior Analyst, TD Cowen

Oh, why they chose three and six.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Why they chose...

Rituparna Roy
Senior Analyst, TD Cowen

Okay

Srini Rao
Co-Founder and CEO, AtaiBeckley

... well, six primarily.

Rituparna Roy
Senior Analyst, TD Cowen

Six, right.

Srini Rao
Co-Founder and CEO, AtaiBeckley

In terms of the primary endpoint, for Phase III, it's all been six weeks.

Rituparna Roy
Senior Analyst, TD Cowen

Yep.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Spravato used, or J&J used with Spravato, a four-week endpoint.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Fundamentally, we did not want to deviate from our Phase II. Our Phase IIb that we read out, as you, as you pointed out in July of last year, had a four-week primary endpoint.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You know, in general, you don't want to deviate too far from your phase II.

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah. That's why we picked the four-week. The FDA was completely comfortable with that. One other point that has come up in several conversations is this you know, the, I mentioned that these are basically being compared to placebo.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

not a sub-perceptual dose.

Rituparna Roy
Senior Analyst, TD Cowen

Yes. Which is, which differs from what FDA had talked about in mix.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Originally talked about.

Rituparna Roy
Senior Analyst, TD Cowen

Yeah. Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Even in our pre-IND meeting with our second candidate, which is VLS-01, the FDA had sort of walked away from that. If you look at the more recent phase III programs, not Compass obviously.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

If you look at MindMed or, Definium now, you look at, Healas, they don't use a sub-perceptual dose.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

They use a traditional placebo. There's advantages.

Rituparna Roy
Senior Analyst, TD Cowen

Yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

You used the word sub-perceptual.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

Investors previously we had talked about sub-therapeutic.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Correct.

Rituparna Roy
Senior Analyst, TD Cowen

I, the, I think the understanding, especially with, maybe, I don't know, the Compass Phase III 1 milligram data, is that they may not be the same.

Srini Rao
Co-Founder and CEO, AtaiBeckley

That's right. There's a big difference here. The 1 milligram dose in the Compass trial and the 0.3 milligram dose in the BPL trial were specifically chosen to be sub-perceptual. The idea is that you don't have a psychedelic effect-

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

of any sort. You don't even have the percepts, you know.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You know, distortions of pers- you know, like, you know, visual-.

Rituparna Roy
Senior Analyst, TD Cowen

Grids.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

I think somebody said grids, like you see grids like in Tron or something like that.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah, or anything really.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

I mean, the whole idea was to have nothing, essentially.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Now, that is different than a sub-therapeutic dose or putatively sub-therapeutic dose. What the agency is now looking for to understand, or mitigate concerns around functional unblinding, is looking at a dose that is still psychedelic, but.

Rituparna Roy
Senior Analyst, TD Cowen

Perceptual.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

sub-therapeutic.

Srini Rao
Co-Founder and CEO, AtaiBeckley

quite perceptual.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Think about it all as basically the 10 mg dose that Compass was using.

Rituparna Roy
Senior Analyst, TD Cowen

Yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

10 milligrams of psilocybin is a recreational dose, essentially, of psilocybin, so it is robustly psychedelic. In the phas IIb, it did not have efficacy, you know.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... compared to the 1 mg comparator. Didn't hit stat sig and effect size was much smaller. Even in the more recent phase III, the COMP005 study, or 006, the same thing was found.

Rituparna Roy
Senior Analyst, TD Cowen

They noted that.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah

Rituparna Roy
Senior Analyst, TD Cowen

even though it looked it was not-

Srini Rao
Co-Founder and CEO, AtaiBeckley

It was not.

Rituparna Roy
Senior Analyst, TD Cowen

... as robust.

Srini Rao
Co-Founder and CEO, AtaiBeckley

That's what you're trying to see right there, because that is what is helping you to, you know, understand that this is not.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

a functional unblinding effect. It's not just because you have a psychedelic effect, you're having efficacy.

Rituparna Roy
Senior Analyst, TD Cowen

That is your 4 milligram dose in ReConnection 1?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Correct. Yes.

Rituparna Roy
Senior Analyst, TD Cowen

That is the, um, perceptual-

Srini Rao
Co-Founder and CEO, AtaiBeckley

Right

Rituparna Roy
Senior Analyst, TD Cowen

... but sub-therapeutic dose.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Well, I would say putatively sub-therapeutic 'cause we've not actually tested it.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

It is absolutely a psychedelic dose. We looked at that in phase I and in other contexts. Has psychedelic effects, not as robust a psychedelic effect as the eight milligram dose.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

Shorter psychedelic effect as well because, you know, you don't have as much drug on board. That's why we're using that as our comparator.

Rituparna Roy
Senior Analyst, TD Cowen

Just because we asked, Compass this, it's only fair to ask you as well. Do you see a role for both doses? Monday morning, our neuropsych KOLs actually said they saw a role for both potentially for 10 and 25 for 360. How do you think about four and eight here?

Srini Rao
Co-Founder and CEO, AtaiBeckley

I mean, ultimately that is, as they say, a review decision, right?

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

It's easier to talk about Compass because they've generated the data.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Right? You know, the 10 milligrams clearly did not separate. I can see providers wanting something else and maybe the FDA acceding to that. I mean, there was a level of efficacy when you compare it, but it wasn't numerically very great, and it certainly wasn't statistically significant, right?

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

I think it was in the phase III, but... certainly in the phase II it was not.

Rituparna Roy
Senior Analyst, TD Cowen

Right.

Srini Rao
Co-Founder and CEO, AtaiBeckley

I can sort of see the FDA maybe putting that out there as well. Really the true effective dose is 25. In the case of MindMed, now Definium, they did a very nice study in phase II that looked at a range of doses.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

They found that 50 micrograms rather, did have psychedelic effects, but did not have efficacy.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

100 had both, right?

Rituparna Roy
Senior Analyst, TD Cowen

Yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

They are also looking at the 50 microgram dose in one of their phase IIIs.

Rituparna Roy
Senior Analyst, TD Cowen

phase III.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Again, I think the same thing will hold. If there's any efficacy, maybe the FDA will push for it. If not, perhaps not.

Rituparna Roy
Senior Analyst, TD Cowen

ReConnection 2, we talked about ReConnection 1, placebo-controlled with a four and an eight, single dose.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Correct.

Rituparna Roy
Senior Analyst, TD Cowen

For ReConnection 2 features a two-dose induction.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yes

Rituparna Roy
Senior Analyst, TD Cowen

... administered two weeks apart, but only the 8-milligram dose.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yes.

Rituparna Roy
Senior Analyst, TD Cowen

Correct? What informed the decision on the timing interval, that two-week interval? 'Cause that's different as well, at least from other Phase IIIs...

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yes

Rituparna Roy
Senior Analyst, TD Cowen

... not necessarily your previous. How do you think that's gonna impact the trajectory of the MADRS curve compared to... 'Cause you've already done a double dose, and you... so we saw like the step function, right?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yes.

Rituparna Roy
Senior Analyst, TD Cowen

How do you think that's gonna impact the ultimate curve?

Srini Rao
Co-Founder and CEO, AtaiBeckley

On the latter question, the data that we've seen so far generally has been where either both doses are open label or the first dose is open label and the second one, I mean, sorry, the first one is blinded.

Rituparna Roy
Senior Analyst, TD Cowen

Blinded

Srini Rao
Co-Founder and CEO, AtaiBeckley

... the second one is open label.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

To your point, in general, the second dose has had a pretty marked effect, right?

Rituparna Roy
Senior Analyst, TD Cowen

Yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

In the case of the Compass study, numerically there was a benefit.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Like the second Compass study, the COMP006, had two doses of psilocybin three weeks apart. There was a benefit seen, but it wasn't nearly as big in the context of a blinded study. Moreover, the overall effect at the primary endpoint of six weeks wasn't that different than a single dose, albeit they had a different comparator.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

One with the single dose was placebo. The second trial with two doses was actually a 1-milligram comparator. Right now I think the jury's a little bit out. I, my expectation is that there's an incremental benefit.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

of having a second dose. What the magnitude of that is still TBD.

Rituparna Roy
Senior Analyst, TD Cowen

Why not try, why not interrogate a 4-milligram double dose?

Srini Rao
Co-Founder and CEO, AtaiBeckley

I mean, that is a slightly different question.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

The FDA could have pushed us towards that. They did not.

Rituparna Roy
Senior Analyst, TD Cowen

They did not.

Srini Rao
Co-Founder and CEO, AtaiBeckley

They were looking at dose response in a broad sense.

Rituparna Roy
Senior Analyst, TD Cowen

Interesting. Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

They viewed dose response as either looking at different doses or looking at more than one dose administration. All of this is dose response, and that's what they were comfortable with.

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

It's not that they have not asked for 4 milligram double dose. They didn't feel the need.

Srini Rao
Co-Founder and CEO, AtaiBeckley

No, no, they did not ask for that.

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

Was it FDA who suggested placebo as the control arm for both?

Srini Rao
Co-Founder and CEO, AtaiBeckley

We suggested it.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

again, based on precedent-.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... as I mentioned, right? Both Definium, Cybin, et cetera.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

That was our... We didn't have a de... We basically presented that.

Rituparna Roy
Senior Analyst, TD Cowen

The rationale being that it would give you your widest separation?

Srini Rao
Co-Founder and CEO, AtaiBeckley

It's not even the widest separation, it's the cleanest analysis, right?

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Let's go back to Compass.

Rituparna Roy
Senior Analyst, TD Cowen

Yep

Srini Rao
Co-Founder and CEO, AtaiBeckley

'Cause they're the other example that's done this. There's always been this outstanding question. It came up again. Was the lower efficacy that was seen in the double dose trial, the second trial, COMP006, was that a result of the, you know, comparing to 1 milligram?

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Would it have been a greater separation compared to placebo?

Rituparna Roy
Senior Analyst, TD Cowen

Yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Don't know. Actually, that's the answer. I really don't know. Also it reduces your comparative safety database, because you need a comparator that's placebo, so you can really ascertain what the rates are. If you start using 1 milligram, that's not the same as placebo.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You have more limitations in the size of your placebo comparator set.

Rituparna Roy
Senior Analyst, TD Cowen

Does that mean... The FDA's okay with this?

Srini Rao
Co-Founder and CEO, AtaiBeckley

For Compass, they.

Rituparna Roy
Senior Analyst, TD Cowen

Yeah

Srini Rao
Co-Founder and CEO, AtaiBeckley

... they clearly were.

Rituparna Roy
Senior Analyst, TD Cowen

Um-

Srini Rao
Co-Founder and CEO, AtaiBeckley

But for us-

Rituparna Roy
Senior Analyst, TD Cowen

I'm sorry, the two placebo-controlled doses.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yes.

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yes.

Rituparna Roy
Senior Analyst, TD Cowen

Does that mean that they are more focused on safety than they might have been before?

Srini Rao
Co-Founder and CEO, AtaiBeckley

I mean, I think they want...

Rituparna Roy
Senior Analyst, TD Cowen

Wanting a bigger safety database?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah, I think they do. I don't know if that came up specifically. I mean, I think there's, you know, generally a focus on safety-

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... and, you know, generating an appropriate safety database. 'Cause again, you know, we're doing intermittent dosing in this case, but it is a chronic condition.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

There's an expectation that these doses, these drugs will be redosed, right? Indeed, that's exactly what we're doing in our open label extension. They want to understand safety as a function of time. You know, they want to get a good size safety database. We have done that with these two trials.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... 350 and 300. As a sponsor, want a good size comparator database. With these two placebo-controlled trials, we have a good size placebo. It just, you know, it allows us to make comparisons and provide counterarguments in some situations that, yeah, well, we saw, you know, XYZ side effect. We saw that in the placebo as well. It wasn't a rate that was in excess. I mean, I think that's powerful.

Rituparna Roy
Senior Analyst, TD Cowen

What are the eligibility requirements for retreating in the open-label extension of the reconnection studies?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah, in general, we're gonna be providing more color on these trials on Friday.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

We have Investor Day on Friday. Kevin Craig, the Chief Medical Officer, will be walking through this in a bit more detail. That said, we're right now not gonna provide a lot more information on the retreatment criteria.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

We will do so at a later time.

Rituparna Roy
Senior Analyst, TD Cowen

Can you review sort of the highlights of the previous Phase IIb data and how this informs your Phase III expectations?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah

Rituparna Roy
Senior Analyst, TD Cowen

now that you have the design?

Srini Rao
Co-Founder and CEO, AtaiBeckley

As I mentioned, the phase IIb also had a primary at four weeks, and that's the reason that we didn't move to some other time point in the phase III program. Basically, it was a three-arm trial. You had the high dose of 12 milligrams, a mid dose of eight, and a sub-perceptual dose of 0.3. Single administration, eight weeks of blinded follow-up, primary endpoint, as I mentioned, at four weeks. What we found is a negative, you know, 6.2 point delta between the 8 milligram dose and the 0.3 milligram dose at the four-week primary that moved down to about 5.5 at the eight-week.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... time point. 12 milligrams originally was put in there. These were both thought to be potentially efficacious doses.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

because they both resulted in robust psychedelic effects. The idea was to look at eight and 12 and understand if there was a therapeutic index difference between those. In other words.

Rituparna Roy
Senior Analyst, TD Cowen

More at 12 than eight.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

the dose response, yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Was there gonna be a benefit, you know, an efficacy benefit that maybe overrode any kind of safety concerns or, you know, changes between those two? In general, both were very well-tolerated. Both doses were well-tolerated. The eight more so than the 1-.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

not surprisingly, right? The efficacy actually numerically was better with the 8 milligram dose.

Rituparna Roy
Senior Analyst, TD Cowen

The eight as well. Yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah, which was interesting.

Rituparna Roy
Senior Analyst, TD Cowen

Did you observe any divergence between the initial responders and partial responders in terms of sustained benefit in the study?

Srini Rao
Co-Founder and CEO, AtaiBeckley

We don't have that analysis as of yet.

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

When can we expect that analysis or additional subgroup analysis in data?

Srini Rao
Co-Founder and CEO, AtaiBeckley

I don't think that we've actually guided on that. I mean, there's a lot of submissions that have been made for posters, et cetera, at various, scientific, conferences and things that are coming up. Then I know there's some things like manuscripts that are also being generated.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah, I mean, it's forthcoming over some of this, without a doubt, over the course of this year.

Rituparna Roy
Senior Analyst, TD Cowen

Can you elaborate a little on the anxiety-related AEs seen in the Phase IIb, and if they were associated with certain patient baseline characteristics?

Srini Rao
Co-Founder and CEO, AtaiBeckley

They weren't seemingly associated with patient baseline characteristics. Let me step back for a second.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

There was an adverse event rate for anxiety that was in excess of what was seen with placebo in the 12 milligram arm.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

As you know, on the order of 14%. It was around 4% with placebo and roughly the same with drug, with 8 milligrams.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

There was an excess seen with the 12 milligram dose group. It didn't really correlate to anything at baseline.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

The Ns were not great, though. I mean, there wasn't a ton of these patients, I think that's partially what's driving it. You know, this, the 12 milligram dose group was around 70-odd patients, and 10% is seven, right? It's just not that many. 10% delta is seven additional. We couldn't really tie it to anything in particular, but you know, obviously something that we did look at in some detail.

Rituparna Roy
Senior Analyst, TD Cowen

What was the time course of the anxiety seen?

Srini Rao
Co-Founder and CEO, AtaiBeckley

It was either during the actual psychedelic event or subacutely beyond that.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Within a week to two weeks.

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You know, one of my speculations is, you know, I mentioned that numerically, the 12 milligram dose had a little less efficacy than the 8 milligram. Not statistically, but you know, numerically. The anxiety, I have to wonder if that was.

Rituparna Roy
Senior Analyst, TD Cowen

If it blunted the efficacy.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah, if it blunted it.

Rituparna Roy
Senior Analyst, TD Cowen

Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

I mean, if it was a little bit too high in a sense.

Rituparna Roy
Senior Analyst, TD Cowen

If people have questions around like, well, what if this is the psychedelic effect associated with better outcomes, you would argue the opposite, that it's more likely to attenuate the clinical benefit than improve it.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You know, it's a really interesting question. We haven't seen a lot of work done on very high doses.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Right? Because, you know, if you go back to Compass and psilocybin, 25 was what most old studies looked at.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Like 25 milligrams. That was essentially the vast majority. There were a few studies that went higher. Vast majority of these academic studies looked at 25. Compass never went higher than 25 in phase I, and certainly not in phase II, and of course, not in phase III. MindMed did a little bit more work going up to 200, but that's still within the dose range that's used recreationally. With BPL-003, we actually did not know what the dose range should be.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Right? Because it's a novel route of administration with intranasal, and, you know, it's, it's just something that there was really no recreational data around, certainly no previous efficacy data on. The phase I went through everything from one to 14 milligrams. 14 milligrams definitely was a little bit too high. 12 milligrams in the phase I was deemed the maximum tolerated.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

As is usual, you know, you wanna put the highest dose you can into a phase II. That was done. In retrospect, it was a little high. This is probably one of the first demonstrations of that, right?

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Where you're actually have gone through a dose ranging kind of approach.

Rituparna Roy
Senior Analyst, TD Cowen

Yeah

Srini Rao
Co-Founder and CEO, AtaiBeckley

in phase I, picked a very high dose, and then found, eh, maybe it's a little bit too high.

Rituparna Roy
Senior Analyst, TD Cowen

There was one case of suicidal ideation, I believe associated with the anxiety. Can you provide context around the timing, severity...

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah

Rituparna Roy
Senior Analyst, TD Cowen

... and attribution of that?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah. This is a patient that was interesting. I mean, it's a patient that had previous suicidal ideation, some intent. Suicidal ideation is never exclusionary in these trials, right? Because suicidal ideation is part and parcel of this. You rule out for intent and you rule out for behavior. This is a patient that had intent and behavior in the past, you know, and some, he had some other weird characteristics. There was an episode of dissociation and some other elements. I mean, they were, almost sounded a little bit borderline like. The patient got the drug. About a week later, started having anxiety, and actually I forgot to mention, had a pretty strong anxiety background as well.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Started feeling intense anxiety. Actually noted that this was going in the wrong direction.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Talked to their doctor. This was in Germany. Got admitted. Had full resolutions of the symptoms without any other intervention beyond a hospitalization by the next day.

Rituparna Roy
Senior Analyst, TD Cowen

Do you think?

Srini Rao
Co-Founder and CEO, AtaiBeckley

About a week later, by the way.

Rituparna Roy
Senior Analyst, TD Cowen

A week. Oh, about a week later.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

Okay. based on the safety data, are you modifying your monitoring metrics or discharge criteria for the Phase III, or some of the follow-up protocols for like the week or two after?

Srini Rao
Co-Founder and CEO, AtaiBeckley

I mean, nothing in specific, I would say. You know, we have a readiness for discharge questionnaire in the Phase IIb. It was very much modeled on sort of the Summary Basis of Approval for Spravato. You know, looking at blood pressure, looking at neurologic, you know, how neurologically intact they are, looking for subsidence of subjective effects. All that stuff we looked at. We have cleaned that up, we're tightening that up because there were some misunderstandings on the doctor's part, you know, of how to interpret certain things, so we cleaned some of that language up. You know, the FDA wants more monitoring around blood pressure, et cetera.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Cardiovascular. We're doing that. That's fine. There, you know, this is a class phenomenon, that there's blood pressure elevations and pulse elevations. We're doing that. No, I mean, nothing that is major. We have, you know, we have reduced the number of visits in terms of, you know, just preparatory type stuff.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... as well as follow-up visits. Yeah. I mean, I think generally everything is pretty much aligned. Nothing major changed.

Rituparna Roy
Senior Analyst, TD Cowen

How, well, Spravato is already operationally intensive for most clinics.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah

Rituparna Roy
Senior Analyst, TD Cowen

... build up.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah

Rituparna Roy
Senior Analyst, TD Cowen

... manage the scale and the appointments, et cetera. How scalable is BPL-003 administration within the existing interventional psychiatry network, and can you talk about time, chair time and time to discharge readiness?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah. The whole idea of both BPL-003 and VLS-01, that's the one that was developed internally, is to have a product that has essentially resolution of psychiatric, psychedelic effects as well as physiologic effects within two hours. The reason that we pick two hours in both cases is that this label for Spravato has that in it, right? It's basically you come into the doctor's office, you are dosed, you have to be monitored for two hours. At the end of that period of time, you're medically assessed, and if you're deemed stable, then you get discharged. Right? That's the label. The idea was to create products that essentially can drag and drop into that. That was the idea.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You know, we're generating the data to support that. It's ultimately a labeling discussion with the agency. what I can say is that, you know, for the vast majority of patients, there is indeed resolution of psychedelic effects and psychological effects and physiological effects within 2 hours. In fact, we had about 85% of subjects in the Phase IIb that met readiness for discharge criteria.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... within two hours.

Rituparna Roy
Senior Analyst, TD Cowen

Got it. Let's move on to EMP-01. That was, you very recently had positive data. This is an R-MDMA.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Mm-hmm

Rituparna Roy
Senior Analyst, TD Cowen

... for social anxiety disorder.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Mm-hmm.

Rituparna Roy
Senior Analyst, TD Cowen

Can you review the key efficacy and safety findings there and talk about the market in social anxiety disorder?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah. Well, Yeah, we'll start with the market first.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

With EMP-01, when we did a couple of years ago was actually we did a phase I trial. We found some interesting features to that. Our initial anticipation when we put this drug into a phase I was that it would be kind of like MDMA. It's the R-enantiomer, as you point out, of MDMA, but it'd be kind of like MDMA, but perhaps better tolerated.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

The reason for that is the S-enantiomer is actually a stimulant, essentially. It has a lot of dopaminergic and norepinephrine release properties.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You know, it's kind of a bad actor. It increases pulse even more, et cetera. It does cause some dose limiting. It is a dose limiting, the driver of dose limiting toxicities, essentially. We thought we'd have something very similar to that. What we found is something that was different. It was robustly psychedelic but it also had these entactogenic.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... activities, kind of like MDMA. Found this really intriguing. We wanted to explore that in a bit more detail. Do more work with it in a larger sample set than you would in a phase I. We also wanted to look at a different indication. You know, 'cause we have two in depression, and a lot of people are doing things in depression. GAD is kind of an extension of depression in a, in a weird way. We wanted to look at something completely different. No one had really looked at social anxiety disorder. There are approvals from back in the early 2000s for social anxiety disorder. There is an endpoint that's regulatorily-

Mm-hmm

approved. It's called the LSAS.

Rituparna Roy
Senior Analyst, TD Cowen

The LSAS, right.

Srini Rao
Co-Founder and CEO, AtaiBeckley

We'll get to that.

Rituparna Roy
Senior Analyst, TD Cowen

This is the SSRIs, right?

Srini Rao
Co-Founder and CEO, AtaiBeckley

SSRIs.

Rituparna Roy
Senior Analyst, TD Cowen

Yeah.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Two SSRIs and one SNRI were approved at that point with this Liebowitz social anxiety scale, which is called the LSAS. Social anxiety is a pretty major, you know, health issue. I mean, it's on the order of 15-18 million people would meet criteria for social anxiety. Even if you think of a more severe subset, call it sort of the treatment resistant group, it's still 6 million, which is about the same as all of MDD. TRD is under 3 million, so you can just get a sense of how big this is, and really no one's playing in the space. That's what got us intrigued by it. Of course, we are breaking new ground.

We are gonna throw a psychedelic into this indication that no one's actually played with an endpoint that hasn't really been looked at in a while.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

That was the context. Of course, because of that context, we decided to move forward with an exploratory study.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Looking primarily at safety to understand the drug a little bit better, then secondarily at the LSAS. That was the design of the trial. Short study, it was six weeks in duration. 70 patients, 35 and 35 placebo versus drug. The drug arm was two doses four weeks apart, and a primary that was two weeks beyond that. What we found in the clinic in the study, and what we, it was about a week and a half ago now that we reported these results, was that there was an 11.85 point delta on the LSAS, which was interesting. It was comparable to what you see with an SSRI, but it was being done at six weeks, and there were some patterns that were different, right?

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm. Versus the, when does the SSRI benefit manifest?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Usually around 12 weeks.

Okay.

You know, eight to 12 weeks is typical, but it's interesting. The LSAS actually can be broken into a fear element and an avoidance element.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

In general, it's measuring behaviors. It's not measuring symptoms.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

That's an important point I'll get back to. With SSRIs, you know, SSRIs, if you, in a broad sense, will kind of initially sort of just tamp down your emotional range, right? I mean, you don't feel fear as much, you don't feel joy as much either. That tamping down that fear leads to behavioral changes over time. You get this pattern where fear is changed initially and then behavior over time. In this case, admittedly in a small study, we actually found that both moved together and they moved rapidly. They moved almost like it was CBT.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

They moved in that six-week endpoint, in that duration. It was actually only two administrations, as I mentioned. Folks who had. The one of the things that really captivated a key KOL, a guy named Murray Stein at UC San Diego, who's a, you know, a real leader in the space of anxiety generally. He's like, "You know, people don't like SSRIs, right?

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You have a lot of issues with the side effects. There are the sexual side effects, the sleep, GI, et cetera. You know, most of these folks don't continue on these drugs, and indeed, that was what we saw. A lot of people in our trials, about 50%, just under 50% of people had been on a SSRI, SNRI.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm

Srini Rao
Co-Founder and CEO, AtaiBeckley

... or a beta blocker or something at some point. It was just a small handful of people actually had to wash off.

Rituparna Roy
Senior Analyst, TD Cowen

Got it.

Srini Rao
Co-Founder and CEO, AtaiBeckley

No one was on it.

Rituparna Roy
Senior Analyst, TD Cowen

Because it's just not-

They don't like it.

They don't like it.

Srini Rao
Co-Founder and CEO, AtaiBeckley

It wasn't enough of a benefit.

Rituparna Roy
Senior Analyst, TD Cowen

They don't like how they feel on it. Okay.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah. The real speculation with that, you know. You know, stepping back, you know, the LSAS itself is primarily measuring changes in behavior.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

You know, mood can change acutely, right? If you're doing a depression study or you're doing an anxiety study, you can get changes within hours and certainly by the next morning, right? It's like, how are you feeling? You can sort of answer. If you look at the LSAS, it's how likely are you to talk to a stranger?

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

How likely are you to throw a party based on your behavior over the last week? Those are tough. They don't move quickly, right? Behaviors don't change as rapidly as symptoms.

Rituparna Roy
Senior Analyst, TD Cowen

Right.

Srini Rao
Co-Founder and CEO, AtaiBeckley

What we noted anecdotally in our trial is that many of these patients had aha moments. They would reflect on the day before and say, "You know, that's... I did XYZ, talked to a stranger, whatever. I wouldn't have done that normally.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

That kind of allows them to build on that success. They had these aha moments. It's almost like you needed some time for this to manifest, that's something else that Murray and David Feifel also commented on. Maybe with a longer trial with more time for the behavioral impacts.

Rituparna Roy
Senior Analyst, TD Cowen

To manifest

Srini Rao
Co-Founder and CEO, AtaiBeckley

... to manifest.

Rituparna Roy
Senior Analyst, TD Cowen

Right.

Srini Rao
Co-Founder and CEO, AtaiBeckley

The other point I think is worth mentioning is that it was a very severe patient population.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Much more so than other trials historically. LSAS, as you know, I mentioned the scale. It goes up to 144. Most of the old studies were in the 80-ish, kind of up to 90 range at baseline. We had the same cutoff criteria or enrollment criteria of around 70. Our baseline score is 108.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Pretty severely impacted folks. The fact that we saw the same magnitude of change, you know, one could argue that because it's measuring behaviors, and if you are more severe, you may have more severe behaviors, more entrenched behaviors, and more of them. It may be harder to move them. This is speculation. We just really don't know that well.

Rituparna Roy
Senior Analyst, TD Cowen

Right.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Something that we're kind of curious about for the next, potentially for the next trial.

Rituparna Roy
Senior Analyst, TD Cowen

What are timelines, for sort of next developments in this program?

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah. We do have other endpoints. We report a top line results only.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

We have other analyses that'll be coming, over the course of the next month or two. These include some more subjective elements, which I think will be interesting.

Rituparna Roy
Senior Analyst, TD Cowen

Mm-hmm.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Once we have that data in totality, then we can make some decisions about what the next study could look like.

Rituparna Roy
Senior Analyst, TD Cowen

Got it.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Yeah.

Rituparna Roy
Senior Analyst, TD Cowen

Great.

Srini Rao
Co-Founder and CEO, AtaiBeckley

Wonderful.

Thank you for joining us, Srinu.

Yeah. Thank you.

Rituparna Roy
Senior Analyst, TD Cowen

This was very helpful.

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