COMPASS Pathways Plc American Depository Shares H.C. Wainwright 28th Annual Global Investment Conference

Thanks so much, Patrick, and thanks for the invitation to be here. Just a reminder, we will be making some forward-looking statements here, so you should refer to our many risk factors in our various filings. We have had breakthrough designation since 2018 based on some of the early work and the resurgence of interest in psychedelics in 2010 onwards. TRD was chosen because that's where both regulators and the founders of the company felt was a very large unmet need. At that point, there were actually no drugs recently approved for treatment-resistant depression. In talking to psychiatrists and patients, it was very clear that there was a large gap there, and hence the decision to go into treatment-resistant depression, which we believe was exactly the right thing, as we'll talk about from a commercial and scale-out possibility.

Steve, I do not know if you want to comment briefly on MOA and what a COMP360 session looks like.

COMP360, which is a synthetic form of psilocybin, is a psychedelic which acts very differently in the brain relative to conventionally known antidepressants, which are typically taken on a daily basis. We have administered COMP360 one or two initial times within our phase III trials, and ultimately, this will be a very infrequently delivered treatment on the order of one to four times per year. The compound initially acts at serotonin receptors, 5-HT2A receptors, and elicits an initial reaction that requires it to be delivered in a supervised medical setting, but with elements of an experience that may be correlated to the positive therapeutic outcomes, which may lead to shifts in depressive patterns of thinking that are durable long beyond the action of the medication in the body.

Sure. No, happy to do that. COMP005 was placebo-controlled, single dose of 25 milligrams against placebo. COMP006 is two fixed doses, three weeks apart, and compared against 10 milligrams and one milligram. In both cases, we saw that at the primary endpoint of six weeks, we saw a statistically significant separation in change from baseline of MADRS of just under four points on both. What we saw was rapid onset, measured as soon as the next day in every case. With the single dose, roughly a quarter of patients with a clinically meaningful response. With 006, with the two fixed doses, 40% of patients with a clinically meaningful response. We now have data out to 26 weeks. We ran these trials fully blinded to 26 weeks, which I think is probably unprecedented in depression.

What we see, therefore, is that one, two, or perhaps three doses produce sustained durability out to at least 26 weeks, because that's what we have at the moment, though we do have some open label data, which we'll come to in a second. Produce sustained durability. The combination of rapid onset, sustained durability, limited dosing is unprecedented in depression and therefore is a potential complete paradigm shift, particularly given the only other drug approved, which is SPRAVATO, esketamine.

We have submitted, I think all of the modules except clinical at this point. We do now have all the data required for the complete the clinical module in hand. But these two phase III studies are close to 900 patients between them, so putting together the integrated summaries is clearly a significant amount of work. That is the final piece, and that we will complete in quarter 4, and we're still on track for that.

Sorry. The blinded period is through 26 weeks, so that was through our part B. We did just release part C data, which took us out to 12 months, and that was open label from 26 weeks out to fully one year. What we saw is exactly like Kabir said is that with one or two initial doses, you saw a very dramatic, very fast, very rapid onset of action. I just want to quickly remind everyone, this is treatment-resistant depression. This is not general MDD. This is treatment-resistant depression, where these patients have, on average, been in their current episode for about three years. So they have tried multiple products and had no success with these products, and we were able to show after one dosing session, a very rapid onset of action within 24 hours.

That is unheard of and unlike anything available for treatment-resistant depression right now. What we saw is that with potentially one additional dose, that durability lasted out through the blinded period of 26 weeks. With the open label data, where patients were all either blinded or on the placebo arm were eligible for an additional dose at 26 weeks. When they received that additional dose at that time period, they were able to sustain that durability out through the end of the year. This is really incredibly promising data. The only other pharmacologic product that's available for treatment-resistant depression right now is SPRAVATO, and that would, on average, take about 25 to 50 administrations in a year.

That's 25 to 50 days off of work that a patient and a caregiver would need to take to go and have this product administered, whereas we have shown data in this patient population, again, a very difficult and hard patient population to have efficacy after somewhere between two and four doses on an annualized basis.