COMPASS Pathways Plc American Depository Shares TD Cowen Novel Mechanisms in Neuropsychiatry & Epilepsy Summit

Good afternoon. Thanks, everyone, for joining us for the COMPASS Pathways Fireside Chat here at the 6th Annual TD Cowen Neuropsychiatry Summit. With us from COMPASS, really big year for you guys. We have CEO Kabir Nath. We also have Chief Commercial Officer Lori Englebert and Chief Patient Officer Steve Levine. Thank you guys for joining us. I will be leading this conversation together with my associate and VP, Athena Chin. And as I mentioned, game-changing 12 months for you guys for 360 and the company at large with the rolling NDA underway. Recent executive order creating tailwinds for development. Guys, you recently reported extension phase 3 extension part C data from study 05, your single dose phase 3 study. And I think high-level at this point, as we approach a potential launch, data suggests that additional doses, whether a second or third dose, provided incremental improvement with benefits sustained up to one year. We'll just spend a few minutes on data before we launch into commercial. But how, what is the data telling you about one retreatment, two retreatments, doses to remission, and how this will reflect in the real world?

Thanks, Rita. I'm actually going to pass that to Steve. I'm just going to remind everyone that we will be making forward-looking statements, and you should refer to our risk factors. But Steve, as a practicing psychiatrist, over to you, please.

Thanks, Kabir. Thanks, Rita. So first, just a reminder on the overall study design, just to set the scene. As you mentioned, this is our 005 study. The phase 3 study comparing our 25 milligram COMP 360 versus placebo in a treatment-resistant depression population. That is those with major depressive disorder who've been failed by at least two treatments in their current episode, and represents a very severe and chronic population with an average duration of illness of at least three years in this current episode, and multiple prior episodes. The overall design of the study included a primary endpoint at week 6 of change from baseline in madras. There was then a blinded portion part B out to week 26, or six months, where participants could receive a single retreatment on a blinded basis. And then part C, which is the one you're asking about, and we've just reported top line on, which is open label, and this is an opportunity to receive a single 25 milligram dose either those who've already been in the 25 milligram assignment or the placebo group. And the key takeaways here is that this really reinforces the profile that's been emerging for COMP 360.

One thing we're really proud of, and it's been very reassuring to see across each of the points of data we've released, is how consistent they've been. In each part of the study, and also between 005 and our second study, 006. And indeed, in this case, what we're seeing is for those who were already in the 25 milligram arm and parts A and B, who may now be getting either a second or a third dose, we see a response to that treatment with similar rapidity and an increased depth of response that is quite durable. And for those who previously had had placebo and now are getting their first dose of COMP 360, it reinforces again that profile we're re seeing of a very rapid response with a very clinically meaningful and significant reduction in madras that is durable out to that 52-week time point and certainly to the point we reported of six weeks post that dose administration. So overall, what we're seeing is that with a generally safe and well-tolerated profile, there is essentially an immediate benefit for those who respond that is very durable. And with now one, two, or three treatments, durable out to 52 weeks.

Got it. Now, let's jump straight into the commercial prep you've reiterated that COMPASS expects to be launch-ready by the end of this year. With approval potentially in first half, how conservative Kabir is this first half timeline? And what modules of the rolling NDA remain outstanding before the NDA is complete at this point?

Yeah. So first half is realistic because there are a number of variables, and I'll get to those. In terms of status, we are completely on track to complete the filing in Q4. I can confirm that. And what's outstanding is the remainder of clinical data. So now we have all the data in-house that we require, but clearly, this is too large phase 3 studies and we do need to integrate some of the data from that, specifically on the safety side. And so really, the work that's going on right now, we have a team working really hard to put together the final integrated summaries, particularly the integrated safety summary. But that is completely on track for completing the filing in Q4. In terms of the variables thereafter, there are limited precedents for an NPV. So there are a couple of questions. First, will the agency still take 60 days to accept the filing? And then while the target for approval is between 30 and 60 days, they may clear that's a target, not a commitment. And indeed, it may be that they issue a standard priority review per DUFA and then look to beat that. But again, there are so few precedents here.

So there's a lot of variability around that.

We have heard the division director call that 30 to 60 aspirational.

And clearly, with a rolling submission and review, I mean, just to confirm, there really is a rolling review. We are getting IRs. We're responding to IRs. It is clear that there is a high level of engagement. We can talk a little bit more.

Kabir, what are IRs? Information requests.

So these are essentially queries from the FDA as to what we've submitted. So what we have submitted is clearly under review under active review. They're highly engaged. But to your point, Dr. Faccioni has said that that is a target, not a commitment. Let me hand to Lori just to talk about the other key variable that goes into that first half window, which is rescheduling.

Yeah, thanks, Kabir. Hi, Rita. So yes, so as a schedule one drug, we will need to be rescheduled once we have an FDA approval because that means that there is medical use approved for the drug. So the federal DEA typically has a statute of taking 90 days to reschedule a product. On average, they typically hit and they go to about 90 days. So that is the expectation is that they do that. However, the executive order back in April asked that the FDA and the controlled substance staff with the FDA work in closer tandem to try and pull those timelines in. How that looks and what that translates to in terms of timing is somewhat unknown. But what I can tell you is we're doing everything possible to help facilitate any potential to pull that forward, including already submitting our A-factor analysis to the FDA so that they could start the review if they wanted to and hand off to the DEA in a timely fashion. Once federal reschedules, then the states need to reschedule. So that they can legally be prescribed and administered in a state. Now, there are several states that will reschedule immediately upon federal DEA rescheduling.

They're called trigger states. Yep, they just follow what federal DEA does. There are other states that require either legislation or regulatory pathways to adjust their statutes. And we've worked very hard over the past two years to pass legislation in these states to make sure that that timeframe is within 30 days. Of rescheduling. So right now, if we were to get approval today, and it were to be rescheduled, we have 93% of the population living in states that will reschedule within 30 days. So just going back for a second, some of these information requests, have some of the information requests been on data that was part of the A-factor analysis, such that it's already under it's suggested that it's already under active review?

We haven't disclosed that level of information around what the IRs are to, but what I can tell you is, yeah, virtually everything that we put in, there is clearly an element of review. But again, to Lori's point, our ability to actually determine the speed at which CSS works, or or indeed when they hand over to the DEA, we really don't have insight into that. So just to come back to your question, the first half is a realistic window. There is clearly an extraordinarily unlikely scenario where we get approval and federal rescheduling by the end of this year. And that's why we have consistently said we would be launch-ready by the end of this year. But again, the likelihood is this will fall somewhere in the first half. And again, as we get closer to completing the submission and dialogue with the agency, we may be in a position to tighten that range. But right now, we're not.