Right into questions. Wanted to dive into your recent interactions with the FDA. You alluded to the possibility of a rolling NDA submission for COMP360 and TRD. Can you talk about what that would look like, and maybe give us a sense of the earliest potential timeline to completion of that submission? Sure. Thanks, David, and thanks for the invitation. Just a reminder, we'll be making forward-looking statements, so please refer to our risk factors. So, yeah, I, I think a little bit of context here. If you look back at the last 12 or so months in psychiatry, you see a whole host of really positive readouts from psychedelic companies, ours included. From traditional psych companies, you see a whole lot of negative readouts. The FDA have also very publicly, the psychiatry division said, more than half of what they're reviewing currently is psychedelics. So in that context, when we took the primary endpoint data from our first study to them in September, they were clear that they wanted to work with us to see how they fulfill their mandate of trying to get transformative treatments to patients. Perhaps earlier than otherwise. And so with that, what we are able to do, we also were able to give them the timelines on our second Phase III study, 006, and the fact that we have now subsequently announced the complete enrollment of that several months ahead of expectation. With those together, we will be in a position to disclose the primary endpoint data from the second study, 006, in the first quarter of next year, together with full details of the primary endpoint from the first study. Taken together, those are clearly the reason to believe we are confident in that data. So with those, the FDA is open to us agreeing a formal rolling submission and rolling review process. Assuming that that 006 data is positive. What that allows us to do is to start to do some work at risk now, which is what we're already doing. They will still want to see the long-term six-month data, 26-week data from the second study. We're expecting that in early Q3, but that then really becomes the final piece of the NDA submission, as it were, the gating item for that, which has us looking at a potential submission sometime in the latter part of next year, and assuming indeed a rolling review and that they have been working on it till then. That's why we are preparing for a potential launch as early as the end of next year, and that really is the 9-12-month acceleration from earlier expectations that we announced last month. You're building in expectation of a priority review here? Yes. We have breakthrough. Yes, breakthrough. The expectation that would be a priority review. With the potential, even with a rolling review, that they beat the PDUFA date, which is, if not from psychiatry, certainly a precedent from other divisions. Okay. That's helpful. So before we go over the clinical program, I wanted to spend some time on the market and really commercialization. So current landscape, I think J&J has cited around 6,000 Spravato treatment centers. So just bigger picture question, what's the extent to which the number of centers are actually growing? How fast are we seeing growth in those centers? And will your launch strategy, at least initially, primarily focus on those centers? Yeah. So that's a great question. So right now, at about 6,000 sites that are registered and set up to administer Spravato. Mm-hmm. Which means they can administer a multi-hour product. That's growing at about 35%-40% year over year. Mm-hmm. That's a pretty exceptional growth. Given they're six years into their launch, they should be reaching about a plateau. They're adding HCPs at that clip. They're adding patients at about that clip, but they're only treating about 60,000 patients out of an eligible patient population of about 4 million, so there's lots of room to grow, and given the fact that we know exactly where these centers are and who is treating at these centers, our commercial launch will be highly concentrated to these centers because the Spravato room is a COMP360 room. Yep. The staff that will be used to administer COMP360 is the same staff that is used to administer Spravato. Makes sense. So you talked about accelerating your commercial readiness plans. Can you provide details on what that means? Sure. Yeah. Very, very grateful that we've done a lot of work already. Yep. So there's been a lot of work done with our strategic collaborations to really understand the barriers that we may face at launch and so that we can get in front of that and try and remove some of those barriers. We've also had MSLs out in the marketplace for about two years now, doing a lot of work educating on treatment-resistant depression, psychedelics, our trial designs, who COMP360 is. We've been doing a lot of government affairs type work. So a lot of the foundational commercial efforts have already been in place. We've also done a lot of HEOR work already, which is quite unheard of for a company at this stage, to prepare for any payer discussions. Accelerating the commercial activities will be bringing on your more traditional type commercial activities, marketing, your commercial operations infrastructure build to get prepared for marketing campaigns, your sales force sizing, structuring, targeting. All of that will be brought on board. Market access most importantly. Mm-hmm. And then, you know, obviously, as time progresses, we'll start bringing on other functions like sales and. So let's talk about the sales force itself. I know this is not gonna look at all like a reuptake inhibitor or a branded antidepressant product. So that's certainly not lost on me. But that being said, how should we think about, you know, headcount and, you know, there's other things behind the scenes that are important here, just given the nature of the treatment or, you know, the patient journey, if you will. There's nursing, there's MSLs, as you pointed out. So just help us understand this overall headcount and the different types of positions you're gonna be filling. Yeah. So if you think about your sales force from a traditional antidepressant launch. Yep. So there are a lot of physicians out there who are prescribing antidepressants. Branded antidepressants require prior authorizations because they usually cost a lot of money. Of those, there are about 50,000 psychiatrists who actually prescribe branded antidepressants. Mm-hmm. That's a very large number of psychiatrists you would have to, you know, cover with a traditional type sales force. With Spravato, we know that there are only 5,000 to 6,000 prescribers who are actually prescribing the product, so your sales force will be dramatically reduced because you know exactly where you need to go. The other piece that we need to think about, though, is referring physicians, so how do we get physicians who need to refer patients into these treatment centers, and so the sales force will need to canvass a little bit of that, but a lot of that can also happen as we grow and gain scale. Yep. There will also be, you know, we will make sure that our MSL field force is sized, probably a little bit disproportionately to other traditional launches because we believe being first to market is very important to make sure that scientific integrity opportunity to discuss with physicians is out there and ready to go. So now, that sort of leads my next question about your marketing message in terms of, you know, positioning versus Spravato. How should we think about that? We need the Phase III to really fully characterize what that will look like. Yeah. But if you just take the one data point that we have from our 005 six-week data, we already are positioning ourselves quite well. Mm-hmm. Spravato, to receive an equivalent efficacy, requires 10 treatments over the time course of six weeks. We achieve what Spravato can achieve with one day of a treatment over that six-week period. And so already from a patient burden and caregiver burden, we are already feeling like we're positioning ourselves quite well. Yep. What about payer access? And this is in the context of 360 being a buy-and-bill product. So how should we think about that? It's not only gonna be a buy-and-bill product. Okay. It will certainly be an option, but it will most likely be specialty pharmacy. It will be. The buy-and-bill will be an element of that. Okay. Mostly, you know, centers that have high volume and want to exercise that option. From a payer standpoint, formulary access for the drug, we feel very good about, mostly because there's only one marketed pharmacologic product out there that has proven clinical efficacy in a treatment-resistant depression patient population. Yep. There are a lot of MDD products out there, but none of them have proven efficacy in the treatment-resistant depression indication. And because of that, Spravato has quite favorable payer positioning and on formularies. They're widely covered PA to label, so typically two failures, and can get approved for the drug piece. We expect we will be doing similar type discussions with payers. Is Spravato pricing pretty logical analog to use regarding pricing of 360, or are you looking at it a little more differently? I usually punt that question. Yeah. mostly because we don't have the full, Of course. The characterization of the clinical profile of the product. Yeah. But it is the only analog out there. But I would encourage people to look at it on a per patient, per annual basis. Mm-hmm. Not a per dose basis. Yep. Understood. Okay. So let's dive into the Phase III trials in TRD. So I think it'll be helpful for people listening in and here in the audience just to review the six-week results from the COMP005 study. Maybe talk to the design of that study. Also talk to the clinical meaning of that 3.6 MADRS improvement that you saw at week six. Yeah. So, the 005 study, the first Phase III, was a two-arm study. Yep. Single dose of 25 milligrams against a true placebo. Designed essentially as a safety study at the FDA's request so that they had a true safety baseline. And the data point that we read out in June was that at six weeks after a single administration, we saw a 3.6 difference in effect size on the madros side. We had been very clear to characterize anything more than three as a win from a clinical perspective. Clearly, it was highly statistically significant. So from a regulatory perspective, it absolutely met the bar. And maybe in terms of contextualize that, I'll turn to Steve as a practicing psychiatrist to see how he sees that in the context of practice. Yeah. Thanks, Kabir, and I don't know that everyone can see your Pacman socks, so I just wanna acknowledge and appreciate those. Oh, thank you. I mean, not everyone, you know, there's a lot of younger folks that don't know what Pacman is. Yes. You know, they did not go unnoticed. All right. I appreciate that. Thank you. Back on the topic. Yeah. Strong thought game going on up here. There's already been some discussion of what's currently available for patients with treatment-resistant depression. Yeah. And in short, that is not much, right? It is Spravato. And so merely because of the size of the unmet need that there are more than or about four million patients with TRD. Mm-hmm. Only 60,000 or so who've been getting Spravato. Primarily what's needed is a new option. Sure. That just means an approved product, which means a stat-sig result and an approval of product. Certainly, that bar is met. When it comes to clinical decision-making, you know, what might a clinician choose for their patient, how they might have that discussion with their patient, it typically doesn't focus on MADRS. Frankly. Yeah. Psychiatrists don't know what MADRS is, and they don't. Yeah. They don't use it in their clinical practice, and so that's where I think the, you know, the fact that we had a highly statistically significant study. Mm-hmm. But also, you know, as Lori said, what we've seen, at least at this point with the primary endpoint at week six, that differentiation from the number of treatments required for Spravato, the fact that we were able to show the same efficacy at week six after just a single administration that would've required 10 with Spravato is highly differentiated in what's going to be most important to. Sure. Patients and their clinicians. Okay. No, that's, that's helpful. So now, just switching gears, you've alluded to the 26-week data that you're gonna disclose, in, you know, the next few months, maybe sooner. Can you just talk to the design of the, of Part B and Part C of that study? That, that context would be helpful. Yeah. No, I'm happy to do that. And then I'm also happy to talk about what we can expect to see with. Yes. That data release in quarter one of next year. So for both studies after Part A, which is, you know, leads to the primary endpoint, that's six weeks in both of our studies. In 005, the first study, which is the first to read out, in Part B, patients remain fully blinded. Mm-hmm. After six weeks, for anyone who has either remitted and then relapsed or who has not remitted, they have the option of another treatment of their original assignment. If you're on active, another active treatment. If you're on placebo, another placebo treatment, or going back on a select group of antidepressants. Mm-hmm. Only one further administration permitted during that Part B through to 26 weeks. After the end of that double-blind period, then, with the same criteria, anyone who has remitted or relapsed and then relapses or anyone who has not remitted is eligible for an open label dose of 25 milligrams in Part C. So with that context, in quarter one next year, we'll have a really important set of data. First, we will have the primary endpoint data from the second study, COMP006, with the two fixed doses. Mm-hmm. Primary endpoint, again, at nine weeks. But the first part of that study run, sorry, at six weeks. Mm-hmm. Primary endpoint at six weeks. Three weeks after the second dose, the Part A of that study runs to nine weeks because nobody is eligible for a subsequent dose until six weeks after the second dose. So we'll have the full data from that. We'll also have the full data from Part A of the first study. Mm-hmm. So far, we've just disclosed one data point, but we'll have the MADRS time curves and so on. Mm-hmm. So we'll have contextualized both primary endpoints from one dose or from two doses. We're confident in the second study, and assuming that's right, that really discharges a great deal of regulatory risk because we'll have both of those primary endpoint data. And then we will have 26-week data from the first study as well. We'll have full safety analysis for that. Mm-hmm. SAEs or AEs above a certain threshold. And in terms of durability, which I know is an important focus, what we'll be showing is at six weeks, segmented remitters, responders, partial responders, non-responders. And then we'll show how those patients track over weeks six to 26. So our SAP shows the tracking of those, and that will enable us to understand what actually happens to patients over the course of those six to 26 weeks. And that's really important from a clinical and commercial perspective. Important to stress from a regulatory perspective, the FDA is not looking for data on duration beyond six weeks. Yep. They are looking for data on the safety of redosing to ensure that that can be done, but they're not looking for data beyond that. Yep. So our SAP contemplates those curves. Also, we will have a week 26 MADRS against the placebo, against the controller. Yep. But I think, again, a lot of that is around really what, how does that inform clinical and commercial practice. And maybe Lori, you wanna comment on that? Yeah. You know, when you think about what you need to promote to physicians is you really need to help them understand how to treat the patients that they're treating. Sure. Giving them that expectations of, if my patient remits by week six, what, what should I expect in terms of time to relapse? Mm-hmm. Or when to redose. If they don't and they get another dose, what happens to them along the way? So us breaking them out into these subsets really is, you know, the data, the data that physicians are looking for to help guide their decision-making. A quick question about one of your studies. So you had a 10 milligram dosing arm in one of those studies. So that's a lower dose. And just wanted to get your thoughts on the rationale behind including that lower dosing arm. Yeah. So that's that replicates the design from our Phase IIb. Right. Only with the second fixed dose, and really, that was something we pioneered, this three active dose study. Mm-hmm. It really was to manage what we knew would be a very substantial discussion around the risks of functional unblinding and managing expectancy. With this three-dose, you obviously have 1 milligram, which acts as the placebo-like, but it's still an active dose. With the 10 as an intermediate dose with a certain potency, but we thought likely not to be as effective, what it really does is it confounds expectancy, and it really helps us manage the functional unblinding, particularly. Yep. In a largely naive population. Sure. So that's what it's there for. The primary analysis is still 25, 25. Yep. Against one, one, and that's really what we're focused on. Got it. Okay. Well, let's talk about safety. You know, there's, you know, perceptual events, you know, hallucinations or delusions. But I wanted to get your thoughts on, you know, severity and on average, how long these took to resolve. Yeah. I can cover that. In the Phase IIb, the most common side effects were headache, fatigue, nausea. Mm-hmm. Generally deemed mild to moderate. In the vast majority of cases, these were resolved by the next day. Certainly in a treatment-resistant depression population, you always wanna consider suicidality. Yep. With the top-line readout from the 005 study back in June, we did have a statement from our independent DSMB that had been reviewing both participants from 005 as well as 006 at that point, well beyond that primary endpoint. Sure. Stated that they saw no new safety signals and no clinically meaningful imbalance between the arms. Okay. And, you know, that's data that the DSMB continues to see on an unblinded basis monthly. They continue to meet on a regular basis. And each time they've told us to continue the study as is. Okay. Switching gears to, I think you had 52-week data from your Phase IIb. But how do you think about duration of, you know, antidepressant effect? I mean, you talked about one treatment. Now, redosing is a, you know, this is a highly heterogeneous population. So in practice, I mean, when to redose is, you know, gonna be a kind of a moving target, and it's probably gonna be individualized. Is that the right way to think about it? I'll start and certainly chime in. Yeah. I absolutely, and that's exactly why we like breaking out by those subgroups. Yep. Because that will help us understand and help physicians understand when to expect to, you know, redose or potentially, watch their patients for relapse. Yep. I do think, you know, if you think about what a label may look like, because we don't know. We don't have the data. Sure. Which is, I'm sure, where you're going with your question. Mm-hmm. You know, we do not expect to have typical constraints around the dosing. What we do expect is that we will likely have, you know, one or two initial doses, and then an episodic after. Got it. Okay. Now, this is one of those products where I would surmise there would be some sort of REMS here. So I don't know if you can talk to that, but I know there's one for Spravato. So, you know, maybe that's a good roadmap of sorts. But how should we think about what the REMS could look like? Yeah. We should certainly anticipate a REMS for COMP360. Yep. To guide early expectations of what that might look like, it would be helpful to look at the existing REMS for Spravato. Mm-hmm. That sets a good precedent, as well as the briefing materials that FDA prepared for the Lykos ad com a couple of summers ago. Sure. Where they laid out, they had a framework for expectations for a different product. I think the combination of those two data points would give a good indication. With that, you know, probably not a lot of granularity around. Yep. The delivery of the product so much as, you know, ensuring along with any identified elements of risk to be mitigated through the monitoring of patients, just basic criteria of the availability of a prescriber and healthcare provider. Okay. Wanna spend some time on the PTSD data, so walk us through that data and the strength of signal here and just next steps for the program. Yeah. So we conducted a Phase II open label study, 22 patients in PTSD. Mm-hmm. Primary purpose was safety because there was clearly concern that a profound psychedelic experience could, in some sense, be retraumatizing or triggering. So first of all, we saw no unexpected or different safety events from anything we'd seen in TRD. This was multi-site across four sites across a couple of countries. So while it was open label, it was, it had some diversity in it. And what we saw was from a single dose, a profound effect. So we saw remission in more than 80% of patients. Mm-hmm. Sustained in over 70% out to 12 weeks. What we also saw from patient interviews was that that was an experience that actually, for some patients, there was a re-experiencing of trauma, but not for all. And so despite that, it was felt, fell in the same kind of paradigm as TRD treatments with psilocybin, relatively reassuring, inner-directed, and so on. So really none of the concerns about this being an inappropriate, you know, for this population. And compared to MDMA, which is the only other significant dataset. Yep. Which required three sessions with MDMA and 15 sessions in total to achieve comparable results, we saw this as a very compelling signal. Yep. So with that, we have now designed a late-stage, potentially registrational study. The protocol is finalized and aligned. We've selected a CRO. We're currently in active recruitment of sites, identification of sites, and so on. We intend to announce that protocol early next year with the details of that study, and that will move into clinical execution in first quarter of next year. I'll hand actually to Lori to talk just about why this is such an important departure for us and why this is so important for patients. Yep. Yeah. This is probably one of the areas of highest unmet need of mental health. Yep. There are 13 million patients out there right now with only two options that are approved for PTSD. They are more than two decades old. So there's been limited to no innovation in this space for many, many years. Mm-hmm. Patients are obviously suffering. About 60% of the 13 million are actually women, even though PTSD gets a high, you know, political commentary and obviously very important subgroup of veterans. Yep. They only account for about 15% of the patient population. Obviously very important and, and something we will focus on, but the majority of patients are actually women. Yep. So this, the potentially the path to an FDA label expansion would be, could be a single registrational study? So yeah. Clearly, the FDA is not gonna agree with you upfront on that. Yep. But I mean, we are clear that by designing a large, fully-powered study, likely an adaptive design, so we would have the option to take an interim look. Mm-hmm. Which allows us either to see does this study need to be bigger or if in fact, if there was, we saw the need for a second study, that could be a decision taken down the line. But our view is the agency is fully understands that the safety database translates, the preclinical package, and so on translates. So we believe with the momentum behind psychedelics now and so on, the right thing to do is to design and execute on this single Phase III study at this point. Okay. And then last question. And I did wanna ask this 'cause you're there, there are other neuroplasticism programs that are looking more broadly, at mood. In other words, MDD, not TRD. And also, you know, looking at GAD. So how are you thinking about broader development of COMP360? Right now, very focused on TRD. Yes. I think it's very important for us to continue, obviously, our focus there. Again, there are only two pharmacologic products that are approved for TRD. So I feel very good about the opportunity for us to prove efficacy in this patient population. Mm-hmm. Obviously, there are opportunities that present themselves in the future once we start collecting real-world data, and understand what that efficacy looks like. We will certainly start to. And. Well. I would only add that there are other psychiatry indications that are even worse than that, such as OCD, such as bipolar II. Yep. We actually have supported ISS that generated signals in both of those. All right. Well, thank you, Kabir. Thank you, Lori. Thank you, Steve, and thanks to everyone in the audience. We'll leave it at that. Thank you. Thank you. Thanks very much, David. Thank you.