COMPASS Pathways TD Cowen Novel Mechanisms in Neuropsychiatry & Epilepsy Summit

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

Thanks, Kabir. Thanks, Rita. First, just a reminder on the overall study design just to set the scene. As you mentioned, this is our COMP005 study, the phase III study comparing our 25-milligram COMP360 versus placebo in a treatment-resistant depression population. That is those with major depressive disorder who have 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 MADRS. There was then a blinded portion, Part B, out to week 26 or 6 months, where participants could receive a single retreatment on a blinded basis.

Part C, which is the one you are asking about, and we have just reported top line on, which is open label, and this is an opportunity to receive a single 25-milligram dose, either those who have already been in the 25-milligram assignment or the placebo group. The key takeaways here is that this really reinforces the profile that has been emerging for COMP360. One thing we are really proud of, and it has been very reassuring to see across each of the points of data we have released, is how consistent they have been in each part of the study and also between COMP005 and our second study, COMP006.

Indeed, in this case, what we are seeing is for those who were already in the 25-milligram arm in 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. For those who previously had had placebo and now are getting their first dose of COMP360, it reinforces, again, that profile we are seeing of a very rapid response with very clinically meaningful and significant reduction in MADRS that is durable out to that 52-week time point, and certainly to the point we reported of six weeks post that dose administration.

Overall, what we are 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.

Yeah. First half is realistic because there are a number of variables, and I will get to those. In terms of status, we are completely on track to complete the filing in Q4. I can confirm that. What is outstanding is the remainder of clinical data. Now we have all the data in-house that we require. But clearly, this is two large phase III studies, and we do need to integrate some of the data from that, specifically on the safety side. Really the work that is 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 NDA. So there are a couple of questions.

First, will the agency still take 60 days to accept the filing? Then while the target for approval is between 30 and 60 days, they have made clear that is a target, not a commitment. Indeed, it may be that they issue a standard priority review PDUFA and then look to beat that. But again, there are so few precedents here that there is a lot of variability around that.

Clearly with a rolling submission and review, Emma, just to confirm.

Yeah there really is a rolling review.

We are getting IRs, we are responding to IRs. It is clear that there is a high level of engagement.