Thanks very much, everybody. It's my pleasure to be moderating this chat with the Definium management team. With me is Rob, Brandy, and Dan. Maybe we'll have Rob start and just give a couple-minute overview of Definium and maybe set the stage of just 2026 is a decently big year for you guys. Then, yeah, I've got a lot of Q&A written out, so we can dive deeper into things. Yeah, maybe just a couple-minute overview for those to get up to speed. Yeah. Absolutely. No. Thanks so much for having us, Paul. Definium, yeah, I think we've been incredibly excited about the year ahead of us. We've been working on our lead asset, DT-120, which is a proprietary form, a tartrate form of LSD or Lysergide Tartrate that we're developing in generalized anxiety and depressive disorder. We are quite excited about everything else in our pipeline, but given the pivotal data from 3 studies coming later this year, most of the attention gets paid there. We as an organization have been really committed to a data-driven approach that isn't willing to accept sort of some of the assumptions or traditions that have sort of characterized our field for a long time. had some really exciting phase II data on GAD and some findings in depression as well that gave us confidence to launch these phase III programs. We have a breakthrough therapy designation for the GAD program, and have been going at a really remarkable clip over the last 4 or 5 years to advance this program to the clinical readouts. Yep. Okay. Great. Well, let's start with MDD, just 'cause that's the next readout, right? Obviously, we'll save a lot of time for anxiety. For MDD, maybe talk about, you know, how you are thinking about probability of success and the data in support of the prospects of DT-120 and MDD. Then on the flip side, right, I think the 1 question we've talked about is just, is showing a signal on MDD within the context of an anxiety study the same thing as trying to test a signal on MDD in a study where the primary goal is again showing an antidepressant effect? I know a lot to unpack there, but maybe I'll leave that with you, and then we can do follow-ups. Yeah. I'll give it a start and then maybe turn it over to Dan to comment as well. Fundamentally, if GAD and MDD as a starting point are highly overlapping, they're overlapping both in terms of how the diagnoses are structured, but also in terms of the scales that are used to measure symptoms. Always point to the reality that item 6 on the Hamilton Anxiety Scale is depressed mood, which is of course the thing you're measuring in depression. The big distinguishing factor is that in major depressive disorder, it's an episodic illness. Patients come in and out of episodes of depression, and when they're in a depression episode, which is required to be in an MDD study, they have really elevated levels of depression symptoms, so it's a measure on the MADRS. Now, the same is going to be true for patients who are not in a depressive episode but have severe anxiety, and 1 can score severe on the MADRS, for instance, with only items that overlap on the Hamilton Anxiety Scale. The degree of overlap gives us a lot of readthrough between these indications, where if we see an effect on one, you read through it a decent degree to the other. In phase II, there is some prior academic data, though we looked at it as more directional and not so much quantitative. In our phase II study, which is a GAD population, patients not in a depressive episode, we still have the baseline MADRS score in the mid- to upper 20's, which would be right at or just very slightly above the criteria to enroll in our MDD study. We saw an over 18-point improvement in depression symptoms, saw a 22-point improvement in the Hamilton Anxiety Scale, and that's 12 weeks after a single dose of drug. On the MADRS, it was 6.4 units better than placebo at the 100 microgram dose and on HAM-A, it was 7.7 points better than placebo. Altogether, we've seen sort of similar trajectory, similar magnitude of change. The thing we didn't see is that, you know, what I think we have to do is have even more room for improvements. When we think of the depression indication, because we were starting in the mid-20s and saw an 18+-point improvement, we're sort of bottoming out the scale. We're getting to a point where we lose discriminatory power, we lose the ability to actually improve the scale any further. That gives us a lot of excitement about seeing patients who are fully in a depressive episode, who likely start with even further elevated in the low- to mid-30's baseline MADRS score. If we see the same sort of response as we did in phase II, it could even give us better sensitivity to detect a change. That's what gives us a ton of excitement. Of course, we don't have a standalone MDD study to base that off of, but you know, given the overlap, we feel very confident. I don't know, Dan, do you want to add? No, I think you covered it pretty well. Yeah. Sure. Thank you. Yeah. Great. Well, to that point, right, like you guys have powered the study for a 5-point difference on the MADRS, right, at 80%, I think, which would be a healthy differentiated effect size. Obviously, you can't compare MDD to TRD, but that would be bigger than what Compass just saw. You know, again, like are you worried at all that that's not that conservative and that that's actually a pretty high bar? Oh, we're not worried, but, you know, we're very focused on it. We've been very thoughtful about how we've approached the execution of these studies, the design of the studies. While we're powered at 80% for a 5-point delta, we would expect just based on the way that the stats work, we would expect that if we saw a similar magnitude of change as has been seen with psilocybin and TRD, that we would get a statistically positive study. Right. I think frankly, if we saw less than 4-point change, it wouldn't be quite as exciting as what we've seen to date. We'd be a bit underwhelmed by that. You know, we think this drug can really perform, and we've sized our studies and, you know, approached these studies accordingly. Makes sense. Why choose MDD and not TRD like some of the others in the space? Yeah. I wouldn't say it was an either/or decision that our MDD population certainly will include a large percentage of people who have had prior treatment and have not been successfully treated by prior drugs. What we've done throughout is to take a broader view of the populations of interest, both in GAD and MDD, to ensure that we're demonstrating efficacy for both regulatory and payer purposes, and of course, we're appealing to the provider and patient communities as well, that is most representative of the people who are overall affected by the illness. That includes, as I said before, a range of prior treatment experience. It also includes severity requirements, so that we're making sure that we're treating folks who are at least in the middle of moderately severe, which means that they're having functional effects from their illness. We get up into, as we've seen in our prior research, people who are pretty severely ill. Rather than a priori specifying a narrower population, we ensure that we capture a representative sample of that population even as we investigate in the broader population. I'll dumb it down briefly and just say that when we look at the current available treatments for anxiety and for depression, those treatments fail most patients over time. Yeah. If that's the case, artificially selecting out the patients for whom the treatments didn't work is somewhat of a worthless exercise because it all works for most people. If that's the case, 1 should choose the broadest possible market and give ourselves the big maximum flexibility in terms of where we could ultimately take the drug. Because the reality is, whether someone qualifies in a clinical trial or not as, quote, "treatment-resistant," most of these patients aren't getting what they need out of the current therapies that are available. Yes. Yeah, for sure. I guess why else would they be in a clinical trial, right? What is your expectation for durability in this? Is there any difference in what you think is feasible from a durability perspective in an MDD population versus an anxiety population? It's a great question. One that we're certainly interrogating most thoroughly in our 12-week Part A of the studies. Everyone remains blinded for 12 weeks, after which they become eligible potentially for open-label treatment if they have moderate or worse symptoms, and that's true in both GAD and MDD. That 12-week bar is quite a long time after a single dose of drug to demonstrate durability. We set the primary endpoint in depression at 6 weeks more for comparability across, you know, most of the approved products and studies that are ongoing. We're very interested in durability, certainly out to 12 weeks. Given the design of the phase III, where patients continue to be observed but are only given open-label drug if they have moderate or worse symptoms return, it gives us an ability of looking beyond that in terms of the durability. We certainly expect there's gonna be different response patterns for some. Hopefully, we see a year or more durability after a single treatment. Think of a lot of subsequent doses, but a good degree of separation between those, so that maybe only a few doses over the course of a year. Okay. Do you expect to have like an interesting anxiety subgroup analysis in this study that I guess would kind of serve as maybe further confirmatory evidence to that anxiety phase II data you put up? We're certainly gonna be looking at the corresponding outcome measures. In MDD, we also look at the Hamilton Anxiety Scale and anxiety as a primary HAM-A, and also look at the MADRS. Yeah, I think what we would expect is definitely a directionally similar change in building this body of the supportive evidence in both directions, so that even if it's a depression population, we're seeing hopefully an improvement numerically in anxiety scores. This is not powered to detect that. Obviously, there's some depending on where the baseline characteristics come in, it may be hard to statistically separate if you're starting at too low of a level. Yeah, we're definitely gonna be looking across the board. As we think about the regulatory strategy and labeling, the more evidence we can see a consistent change on both of the domains, it gives us a lot of confidence that we're seeing a true effect on both anxiety and depression symptoms. Okay. Great. Maybe switching gears to GAD, do you wanna just kinda give a quick overview of the phase III program scope, status of the studies, and then, yeah, we'll do some follow-up? Yeah. Building off of successful phase II study, we did the only comprehensive dose response study that's been done in this field. We looked at 4 different doses of drug versus placebo. The 100 microgram dose was clearly the appropriate and the maximally efficacious dose. The one with the 200 microgram dose, the best tolerability profile and such. We used that study to justify a dose selection to design a phase III study. In phase II is our 22-point, almost 20.9 improvement on the active drug, which was 7.7 is better than placebo. Based on that, though, we designed complementary phase III studies, the first of which is a head-to-head. A 100 micrograms versus placebo. The trial was called Voyage. You can enroll about 100 patients per arm. Second study is Panorama. It is also statistically a head-to-head, but we include a third arm in the study, which is half the allocation, so 50 patients in that arm who receive 50 micrograms of drug. That's sort of a decoy dose to try to confuse people who feel the effects of drug on the day of dosing, so they can't be certain they're actually getting the real dose of drug. Kinda mitigate this expectancy and functional unblinding, all these kind of concerns that have come up in this field over the past several years. Both studies power to detect a 5-point difference at 90% based on some assumptions. Both studies include a blinded sample size re-estimation, which we just passed in VOYAGE, and announced the data from a few weeks ago where we saw both a better patient retention rate, so a 10% not evaluate rate and a better variance in the data at 6.7 unit standard deviation, which ultimately at those levels give us 99% power to detect a 5-point difference. Gives a lot of confidence going into 3 arm. Can I ask you a question? Is a better variance a good thing or are we hoping for like a polarized outcome between drug and placebo? I don't know if I'm understanding the concept of variance the right way, but that's always something that people ask, so maybe you can clarify the interpretation of that. Yeah. It's a big question. On a blinded basis, it is impossible to know which. The blinded variance is the sum of the inter and the intra-group variance. The reality though is that within all sorts of practical limitations, that blinded variance is wildly dominated by the intra-group variance such that. Right is going to be much more valuable than some. Okay. That's really good context. Yeah. Okay. Makes sense. You know, and then as you think about this phase III program, obviously it'd be great if both studies work, but do you feel like the 2B already counts and that you only need to go 1 for 2? How well do we kinda understand this regulatory cushion that you've de-risked it all? I'd say we are very confident and very committed to getting positive studies from the ones we're conducting and reading out soon. Of course, depending on the nature of the readouts and so forth, you know, we have really strong evidence to date, and based on the data that we generate in phase III, we're gonna have regulatory discussions accordingly. We know that there's a climate right now that's, you know, quite accommodating, and we have a lot of supportive evidence that can be true whether we have 3 studies or, you know, or less. We're pretty confident going into these readouts that we'll be able to demonstrate positive results across all 3 which is just getting started. There's been like a lot of conversation in psych about professional patients lately. I mean, it's been a conversation for a long time, like Neurocrine was talking about this when they were in phase II and TD. J ust as it relates to like a trial execution thing, can you talk about like the specific things you're trying to do from a risk mitigation perspective to not have the studies fail your drug either in MDD, GAD or both? Yeah. We make an effort not to blame the participants in our trial for things that don't go our way. This is a classic move in psychiatry. You blame the placebo for being too strong. You blame the patients for not, you know, for not being the right people. That's on us, right? That's on our sites. Throughout the conduct of these studies, we're incredibly cognizant of making sure that we capture the population we intended to. We write the studies in a way that is meant to investigate the population we're interested in, and then everything we do from getting that protocol out into the world to when we get data back in is about ensuring that the people we are working with in the studies are those out. We do that through a few different methods. We mostly truly rely on double-checking everything so that when we have new participants enter the study, they get diagnostic assessments at a site level, but they're also getting a remote third-party diagnostic assessment, and they're getting severity assessment done by another party even who's doing another blinded remote assessment so that everybody at the point of entry is getting at least 3 different entities independently assessing them. That increases the probability that the diagnosis they're reporting is in fact the right diagnosis. Across those assessments, across labs, across all of the instruments we use, we're looking for directional alignment, magnitude alignment. If anything doesn't look right in the alignment of these things, then we put the brakes on that participant and make sure that we're seeing what we want to see. This includes review of all of their documentation, short of identifiers of course, by internal medical staff on our team as well. This is at the end of the day, working with sites we trust in a continuous way and constant presence with those sites. We are the constant communication with the sites, sometimes to their enjoyment and other times maybe less so. We're there for them and we're there with them, and then having our own review of everybody we enroll. Incentives are aligned and everybody wants to run the study exactly the way we intended it to be run. Right. Okay. Well, let's try to hit a couple commercial questions. Maybe to start, right, like I think a lot of investors to make it easy are taking the number of SPRAVATO patients and just doing a back of the envelope on the other companies and assuming that number expands. I t's just it's easy math, but you know, GAD is different. It's also similar 'cause there's comorbidity with depression, but just like how do you help people size the GAD market? Like a patient model on the frequency of anxiety gets overwhelming. Like what's the actual funnel of patients that could actually get this and how much does that overlap with the SPRAVATO pool versus actually serve as a distinct population. Yeah. I think you can think of the SPRAVATO pool of patients who is labeled for treatment-resistant depression in the presence of suicidal ideation behavior, right? We think of that as the narrow sliver of 1 of the 2 populations that we're showing. The numbers do get quite large when you look at these populations. When you look at people who would likely even pass the acute prior failures, we're still talking in the low teens of patients with both MDD and/or GAD who have failed through 2+ treatments. These markets are absolutely and tragically far too large, and so the numbers start to look silly, but we have to trust the realities of who is out in the world. When we think of that and think of as we as a business look at it as an opportunity, of course, even treating tens of thousands of patients would be a remarkable success for us as a company. That's not really success how we measure it. We want to actually have what we believe is a game changer and deliver on the magnitude of benefit that, you know, if we really have the best-in-class drug and one that can drive the kind of treatment benefits that we've seen to date, and it gets everyone excited, this needs to be in the hands of as many providers as possible, and we really aspire to meaningfully have an impact, which can't be accomplished if we're talking about a few thousand people at a time. You know, when we talk about 10 to 15 million patients who would be eligible, you know, that is an eye-watering kind of number, but it is the real number, and it's an opportunity that we think in the years ahead we'll be able to make a dent. How do you get comfortable with the duration of the inpatient stay for LSD from a logistical scalability perspective and an economic perspective for these sites? Yeah. One of the easiest is to just go ask sites and, you know, you'll get a range of answers. By and large, what we hear is that, especially from sites who both have clinical practices and have worked with 120 in clinical trials, and right at this point we've had a lot of investigators who have done a lot of treatment sessions, whether it be blinded or some open label treatment sessions in our studies. The predictability of the patient experience, the predictability of running a practice and delivering a drug where you have a reliable on-ramp and off-ramp, where 1 patient could be in under observation for a day and that afternoon, end of a workday, they're going home and going about their lives, is something that is not only attractive to the providers and quite efficient for them from an operational standpoint. It is really attractive for patients. Patients are tired of being shuffled through and rushed out the door. The concepts of trying to have fast turnover and, you know, speed them through so they can crank out patient after patient, it's a convenient thing to try to plug into conceptually, but it is not a reflection of these drugs. It's not how they're going to work, we don't think, and it's really not what patients deserve. If we're going to be able to drive a multi-month durable effect, you know, I think patients don't really care whether it's a couple hours or spending one day to get better for months at a time. Sorry, I muted myself. Makes sense, Rob. Thanks. We only have limited time here. We could obviously talk about a lot of these questions for another half hour, but maybe the one sort of last thing I still get from people is on the regulatory side in this space. That's just related to, like, beyond showing evidence of efficacy in a parallel group study. You know, what do you need to satisfy the FDA on durability and kind of direction on how to redose one of these drugs? You know, there's the whole functional unblinding question too, which I know you love to answer. Maybe just hit those quickly for the sake of completeness. We don't have time left in the workday to cover functional unblinding and how silly of a concern that tends to be. I mean, I'll sort of cover that one first, which is functional unblinding happens with every psych drug that has ever been approved. It's never been a problem before. For the drugs that are in this loosely defined category, that being MDMA, which has gone to a decision, look at the MDMA CRL, we haven't found an instance of functional unblinding being a reason for regulatory concern. Psych drugs where 20 milligrams of Adderall is a dose that people can feel. Most psych drugs have that effect. We have the same one. We've gone to great lengths, probably more than anyone had in the past to sort of mitigate that and address, you know, that concern. In terms of, you know, regulatory durability, we had a great dialogue with FDA. They've been really engaged throughout process and really great partners in the true sense of that word. What we have agreed is that if we can show a 12-week durable effect, that is as long as anyone could reasonably ask to do after a single dose of drug. We're really following patients for a year, and what happens after that 12 weeks is going to be informative, and that's what you need for labeling, right? Is you need to be able to inform prescribers. You don't need to answer everything in a statistical contrast to be able to say, "Well, you know, placebo got dose this many months less thing," but that's not what that Part B is intended to do. In order to characterize the safety, in order to inform retreatment patterns, part B of our studies where patients can get up to 400 milligrams of drugs designed in a thoughtful conversation with FDA. We feel with the data we'll have accrued at the time of, you know, the readout, hopefully an NDA submission, we'll be in really good shape to be able to appropriately inform prescribers. Yep. Okay, great. Obviously a lot more we could talk about, but in the last minute here, anything else you guys would like to add? You wanna talk about cash runway or, you know, anything else I think would be good. Yeah, happy to do that. We ended the year with $412 million in cash. Really helpful to do a raise in October that gave us additional funding so that we could do a lot of preparation while we are anticipating these top-line data readouts this year. Things like NDA preparation, our, you know, priorities for market access, KOL education, we have been running full steam with all of those, and we are looking forward to hosting an investor and analyst day on April 22nd, where we will go through our expectations for top-line data, as well as the commercial opportunity, and look forward to seeing you there, Paul, and many others as well. Awesome. All right. Well, thank you very much for joining. Really appreciate it. Really appreciate it.