COMPASS Pathways Plc American Depository Shares Morgan Stanley 24th Annual Global Healthcare Conference

It is great to be here. And just our own disclosures, I will be making forward-looking statements. We will be and please refer to our various risk factors. So COMPASS was really founded to make psilocybin available through the medical model with broad and equitable access, and that is exactly the purpose we have been engaged on now for the last nearly decade. One of the things that I think is key and perhaps investors still do not fully appreciate is the decision to go into treatment-resistant depression. So we are working in a patient population with chronic recurring depression, a population that is really very different from an MDD population, where many other things have been approved, and that is a key point of differentiation, and Lori will talk more about that in a moment. As you said, we are in a great place right now.

We are going to complete the submission in Q4. We have a Commissioner's National Priority Voucher. I am sure we will talk more about it, but really the agency is extremely engaged with us. One thing we have to acknowledge as the first likely psychedelic to be approved, we are doing a lot of the heavy lifting. So where we are going, others will come behind us. So when we talk about not only the way we have designed our trials, you will actually see imitation is a great source of flattery. Lots of other people have designed similar trials. Indeed, the FDA's own guidance for psychedelic trials really described our phase III program.

We believe in many ways we have been pioneers, have set the standard in this field. We are just very excited now to be within sight of the next huge milestone of potential approval and launch.

Yeah, happy to. Right now, there are currently 55 MDD approved products being used on an annual basis. Five of those are branded, and they are all pricing at innovator pricing. TRD has one, and that is SPRAVATO, which is currently being used. The reason that this is such an important difference to make is there are 4 million patients who actually are TRD. TRD is traditionally defined as the failure of two antidepressants. So 4 million patients out of the 13 million MDD patients that are currently being drug treated is a very large patient pool of patients who only have one option currently indicated for. The difference between MDD and MDD in terms of being able to have this efficacy set that we have proven in this patient population is and comes down to payers.

Payers will, because this product is the only other one that will be approved at the time, will most likely cover us PA to label. That is how SPRAVATO is used today. Again, SPRAVATO made $1.7 billion last year, and only treated 100,000 patients. So there is tremendous pricing power potentially with payers and having efficacy in this patient population specifically.

Absolutely. COMP005 was two arms, single dose of 25 milligrams against true placebo. That was really designed as a safety study, and the dialogue with the agency was around truly establishing a safety baseline. Again, remember, we were the first psychedelic to enter phase III, so that was part of that dialogue. COMP006 is the same three arms that we used in the phase IIb, so the 25 milligram, which we believe was the active dose, 1 milligram replacing the placebo, so not an inert placebo, but something that would have some potential subjective effects, and then 10 milligrams chosen as an intermediate dose, which first, in a fully naive population, would actually help from a blinding and confounding perspective.

We know the agency likes to see a clear dose response to show that this truly is a drug effect, so that was the other part. That is two fixed doses- 3 weeks apart.

Primary endpoint in both 6 weeks. Also both running fully blinded to 26 weeks, which is, I think, unprecedented in depression trials, but certainly pretty unusual. We really knew even though we designed these trials before the FDA issued their draft guidance, the durability was going to be key, not only from a regulatory perspective, but as we'll come on to discuss, absolutely from a commercial perspective as well.

Yeah. I'll briefly touch on the data and then hand to Lori to talk about how we see that translating into real clinical and commercial practice. In both studies on the primary endpoint, highly statistically significant results, we saw a separation of just under four points in the change from baseline on MADRS. Again, in this population, and again, just to perhaps belabor the point of this Treatment-Resistant Depression population, the average duration of the current episode of depression was three to four years in our trial. This is truly a population that, while to enter the trial, had to have failed at least two antidepressants in the current episode. Typically, over the course of disease, have tried multiple medicines and really nothing else is working. So very much a chronic refractory population.