Welcome to the Definium Therapeutics phase III EMERGE Top Line Results call. We ask that you please hold all questions until the end of the prepared remarks, at which time you will be given instructions for the question and answer session. As a reminder, this conference is being recorded today. If you have any objections, please disconnect at this time. I would now like to pass the call over to Rob Barrow, Chief Executive Officer. Please proceed. Hello, everyone, thank you for joining us this morning. As the operator said, I'm Rob Barrow, CEO of Definium, joined today by our Chief Medical Officer, Dr. Dan Karlin, our Chief Financial Officer, Brandi Roberts, and our Chief Commercial Officer, Matt Wiley. We couldn't be more excited to be here with you this morning to share the landmark results from EMERGE. Before we get started, please note that on today's call, we'll be making certain forward-looking statements. We'd encourage you to review our SEC filings for a discussion of the risks and uncertainties associated with these statements. Opportunities to share results like these today are exceedingly rare. We believe the findings being presented today have the potential to redefine what patients can expect from the treatment of Major Depressive Disorder and position DT120 ODT as a potentially best-in-class product. Major Depressive Disorder and Generalized Anxiety Disorder impose an enormous burden on patients, families, and our society. Despite decades of research, the need for transformative new therapies remains. Before going any further, I want to take a moment to thank our study participants, investigators, study partners, and our incredible team at Definium for making all of this possible. I am deeply appreciative and honored to work together with you and for your trust, commitment, and belief in what we're striving to achieve. Your efforts have brought us to this remarkable moment, and most importantly, have brought us one step closer to making our dream a reality. We have an ambitious vision at Definium and believe that profound change in psychiatry is achievable. We set a high standard for our program, seeking to prove that a single-dose supervised in a clinical setting of DT120 ODT can deliver rapid, robust, and durable efficacy and can offer new hope to the tens of millions of individuals living with depression, anxiety, and other mental health disorders. We're of course here today to discuss the top-line results from our phase III EMERGE study of DT120 ODT, our first pivotal study for the program. It's my absolute pleasure to share highlights from the readout before turning the call over to Dan to discuss these results in greater detail. The EMERGE study met all primary and key secondary endpoints and was highly statistically significant, with a P value of less than 0.0001. This was represented by an 8.1 point placebo-adjusted improvement on the MADRS at week six, which was the primary endpoint in the study. This staggering efficacy was durable for the full duration of Part A, with a 7.3 point placebo-adjusted improvement on the MADRS observed at week 12, and was further complemented by the rapid and significant improvements observed on the CGIS as early as day two. DT120 ODT was generally well-tolerated, with no SAEs or suicidality signal in the study. Importantly, through our intentional granular approach to characterizing the dynamics of each dosting session, we were able to share further clarity on the efficient treatment session dynamics of DT120 ODT. The average time for participants to clear the end-of-study checklist was 5.8 hours, with over 50% of participants clearing at hour five and all participants clearing the checklist by hour eight. At a recent investor and analyst day, we shared our belief that a durable response of at least four points would represent a potentially best-in-class profile in the context of both historical and modern antidepressants under development. Today's results far exceeded those expectations with efficacy at week six that more than doubled that bar and which stands out as one of the largest placebo-adjusted effects ever observed in a pivotal study of depression. We could not be more excited by these results and what they mean for the potential to deliver our mission and for the millions of patients in need. With that, I'll turn the call over to our CMO, Dr. Dan Karlin, to discuss the results in greater detail. Dan? Thanks so much, Rob. EMERGE is a phase III study that consists of two parts. The initial part, Part A, is a 12-week randomized, double-blind, placebo-controlled. This is a single-dose paradigm with DT120, 100 μg. This is a monotherapy. Participants were tapered off of any background antidepressant or anxiolytic, and those medicines were washed out prior to participation. There was no psychotherapeutic intervention that went alongside the drug, so it's truly a single-dose study of drug versus placebo. The primary endpoint for the study was the MADRS at week six, assessed by independent central raters who were blinded to treatment allocation and to visit number. The second part of the study, Part B, was an extension phase where after that first 12-week double-blind period, participants remained in the study for 40 additional weeks and were eligible to receive up to four open-label doses over those 40 weeks if they were eligible by having a MADRS score of 20 or higher, meaning that they were moderate or worse on that scale. 149 participants were randomized, and all received a double-blind dose of DT120. Of those 149 participants, 84% completed Part A, which was completely aligned with our expectations for the study and consistent with historical studies in the field. The demographics of the participants who participated in this study were well-balanced and representative of the MDD population. Notably, you see here that we enrolled participants with a high degree of severity, as shown by a baseline MADRS of 34.5, which is consistent with a baseline CGIS of 4.8. This puts these participants well into the severe category on the MADRS. As anticipated, the extent of prior psychedelic use in the study is consistent with the general population, which is estimated to be about 15%. Prior LSD use is only 4%, which is also epidemiologically consistent with the general population and a small enough number not to confound any outcomes of the study. Another look at disease severity here. We see that 34.5 MADRS, along with a breakdown of the severity of the patients in the study, with only 20 or so percent at moderate and the remainder in the severe category. You also can note here the history of antidepressant use among these patients divides them nicely between people with zero or one episodes of prior antidepressant use and people who have been failed by two or more antidepressants. Clinically, we call that 2nd category treatment-resistant depression. The length of the current depressive episode is consistent with the disease definition of MDD, with the majority of patients having a current depressive episode of less than one year and a fair number of the patients, approximately 25%, having a current depressive episode length of one to two years. You'll note that none of these patients had an episode longer than two years, at which point we start to look at diagnoses other than major depressive disorder. The number of lifetime depressive episodes is nicely distributed between people who are relatively early in their course of illness and people who have been dealing with major depressive disorder for a significantly longer time. At every measured time point, the treatment group statistically and clinically exceeded the placebo group. That treatment group showed a difference at every time point with a p-value of less than 0.0001. There are a few categories that we look at when we describe the effect of the drug. Robustness. At the primary endpoint, we saw an 8.1-point separation from placebo. That primary endpoint was measured at week six, which is the standard time point for showing antidepressant efficacy. We looked at durability. That single dose was effective out to week 12, where we saw a 7.3-point differentiation from placebo with that same level of statistical significance. Rapidity is an incredibly important feature for people suffering from major depressive disorder. As soon as week one, the first time point where we measured the MADRS, we saw a very strong 17.6-point total change from baseline and 14.2-point differentiation from placebo, which of course is also strongly statistically significant with a p less than 0.001. This really remarkable rapid and robust response and tremendous separation from placebo give us enormous confidence in seeing this drug effect over time. Another way of measuring disease severity is the CGIS. We see that the CGIS curve describes effectively the same response as the MADRS. What's most notable about this is that the CGIS is assessed by site-based raters, while the MADRS, as I said previously, is assessed by blinded centralized raters. These are two very different ways at looking at the same construct, which is how affected by MDD is the patient through the course of the study. These two different instruments assessed by raters with two different conditions describing effectively the same curve gives us tremendous confidence that the measured drug effect represents real change in these patients. Another way of looking at the MADRS is remission and response. Here you see remission numbers for a MADRS of less than or equal to 12, which is generally thought to correspond to no clinically significant depression. Our remission numbers there are 24% of the population at week six versus 3% for placebo. We also look at mild or better. Mild and better will come up as we talk about part B, where the trigger for treatment in the open label opportunities for retreatment is moderate or worse. Effectively in part B, we're treating to mild or better. At week six, we see a rate of mild or better of 41% in the treatment group versus 13% in the placebo group. Another way of looking at the MADRS scores, which rather than using absolute cutoffs, uses a relative cutoff to where a patient starts at their baseline score. Here we see the conventional definition of response of more than 50% change in score. 35% of treated patients versus 7% of placebo patients reached that 50% cutoff. Each of these measures of remission and response is highly statistically significant. We looked at subgroup analyses to ensure that no subgroup was disproportionately responsible for the observed overall effect. Across each of these analyses, we did not identify any subgroup that could be independently responsible for that observed effect. This is particularly notable when we look at previous MDD medications. As I said before, we had a significant number of folks who had two or more prior medication failures, and in that case, we did not see a disproportionately high or low treatment response in that group relative to people who had been failed by one or no medicines. Overall, DT120 ODT was well-tolerated, and the adverse event profile was consistent with what we've observed in prior studies. 99% of adverse events were mild to moderate in severity. Most treatment-emergent adverse events occurred on and resolved on dosing day. No treatment-emergent adverse events led to study withdrawal. There were no serious adverse events. There was no incidence of suicidal or self-injurious behavior, and there was no indication of increased suicide risk or suicide-related risk in the study. Here we see a more detailed view of treatment-emergent adverse events. As I said previously, these treatment-emergent adverse events were mild to moderate in severity, with one exception for a severe adverse event that was an episode of exacerbation of chronic back pain that occurred six weeks after dosing. One thing that's notable on the TEAE slide here is that we have a 99% rate of treatment-emergent adverse events in the treatment group. We have an expected profile with treatment-emergent adverse events, and the fact that we are picking these up in the study is suggestive of a high-quality clinical conduct at the study sites. There were no treatment-emergent adverse events that led to study discontinuation. These are the common treatment-emergent adverse events, and these, as I said before, are completely consistent with what we expect from the study drug. These are perceptual, affective, thought processing, and behavioral changes that are expected during dosing day and generally resolved by the end of dosing day. Rob mentioned this before, but we think it's really important to reiterate. The treatment session dynamics are remarkably constrained in the 5 to 8-hour window. We used a structured end-of-session checklist that assessed participants to safely leave the treatment session. As Rob said, 57% of participants cleared that end-of-session checklist at hour five, and 100% cleared by hour eight. We believe this translates very cleanly into clinical practice where the end-of-session checklist can be easily implemented under any subsequent REMS program. Now we get to talk about Part B. As I mentioned before, this is the 40-week extension phase where participants have the opportunity to receive up to four open-label treatments if they qualify by having a score of 20 or higher, representing moderate or worse symptoms on the MADRS. At the time of our analysis, 94 participants had entered the extension population in Part B. Based on the way that these studies enroll with an increasing rate of enrollment over the course of the conduct of the study, we had a limited number of participants who had progressed beyond week 28 at the time of the data cut we're discussing today. Therefore, our ability to meaningfully discuss data beyond week 28 is somewhat limited. What we'll focus on today are results through week 28 and the participants who reached that point. The demographics of Part B are obviously going to be similar to the demographics of Part A from which they are selected. With lower MADRS scores representing both the treatment and placebo effect of the participants who completed Part A. This treatment pattern slide gives you a sense of how participants entering Part B have progressed through the first three months of Part B with those opportunities for open-label treatment. As we anticipated, multiple treatment patterns are emerging, with most participants receiving only one or two open-label doses across the first six months of the total study. Here we see longitudinal efficacy moving from Part A to Part B. With the availability of open-label dosing, we see continued reduction in MADRS scores in both groups. Those receiving placebo in Part A begin to converge with those who receive DT120 ODT in Part A. The results from this Part B give us great confidence in the real-world treatment paradigm and give us our first sense of potential longer-term multi-dose efficacy and durability for DT120 ODT. As with Part A, we can look at response and remission over time in Part B. What we see here is that across each of those measures, the treatment groups converge at about 50% mild or better, MADRS less than or equal to 12 remission, and 50% response. This, again, gives us enormous confidence in our ability to ultimately show multi-dose drug efficacy and safety in the real world. Thank you very much, and I'll turn it back over to Rob. Thanks so much, Dan. Our goal at Definium is to enable a new treatment paradigm that could profoundly reshape clinical practice in psychiatry. We believe the landmark results shared today are another important step in pursuit of that goal. With the incredible momentum heading into our upcoming phase III readouts, beginning with the VOYAGE and PANORAMA studies in the months ahead, could not be more excited for the future of the DT120 ODT program and the patients we aim to serve. Given the enormous unmet need in these areas, with over 4 million patients failed by today's treatment options, the strong desire from patients and providers in the large and growing sites of care, we believe there is a unique opportunity to deliver significant impact and value in the years ahead. We see two distinct drivers of this value creation opportunity: our continued commitment to excellence in clinical and regulatory execution as we continue to advance our pipeline and pursue regulatory approval for DT120 ODT, and setting the standard for commercial impact and execution to bring this clinical promise to patients as impactfully as possible. We're working tirelessly to build Definium into a psychiatry powerhouse that can set a new standard for what patients and providers can hope to expect from care. Before we go to Q&A, I want to say again a special thanks to our team at Definium. We've built an organization of exceptional people who are deeply passionate about our mission and the patients we serve, and none of this would be possible without your unwavering dedication and tireless effort. It is an honor and a privilege to work alongside each of you every day. I cannot wait to see what the future holds for us. With that, we'll open up the Q&A log. Thank you. Thank you. At this time, if you would like to ask a question, please click on the Raise Hand button, which can be found on the black bar at the bottom of your screen. When it is your turn, you will receive a message on your screen, and then you will hear your name called. Please accept, unmute your audio, and ask your question. We ask that you please limit yourself to one question this morning. We will wait one moment to allow the queue to form. We'll take our first question from Andrew Tsai with Jefferies. Please go ahead and ask your question. Good morning. Big congratulations on the data. I really appreciate you taking the question. In this study, can you remind us what percentage of MDD patients also had comorbid GAD or elevated anxiety? What did you see on the HAM-A scores for that subgroup of patients? Just thought I'd ask so we could have another supporting data point for your phase III GAD readouts coming up very soon. Thank you. Thanks so much for the question, Andrew. I'll turn it over to Dan. Thanks, Andrew. It's a really good question. We had observed a GAD diagnosis rate of about one-quarter. 25% of these patients had a GAD diagnosis, which is actually pretty high. In an MDD population, due to the features of the diagnosis, GAD is often not diagnosed. While many GAD patients will have received an MDD diagnosis along the way, that has more to do with epidemiological features related to making the diagnosis than actually having the experience of GAD. While we don't have the HAM-A data available in this top-line readout, we do know that there was a high level of background anxiety, in part because MADRS also assesses for anxiety. What we see consistently is that in folks with higher symptomology, whether that's depressive symptomology or anxious symptomology, we are able to move those scales further. We're really confident in our ability to move anxiety scores in the MDD population. Of course, based on our prior phase II research, we know that we are able to move anxiety scores in folks with GAD, not in a major depressive episode. Great. Thank you. Makes a lot of sense. Congrats. Thanks, Andrew. We'll take our next question from Marc Goodman with Leerink. Please go ahead and ask your question. Yeah. Good morning. I'm curious about this end of session data that you have, hour five, six, seven, 8% of patients that lasted that long with respect to their experience and how you expected this to play out with respect to the label, as well as the real world and how different you expect that to be and just your conversations with FDA about it right now. Thank you. Yeah. Thanks so much for the question, Marc. At a high level, it would be, of course, premature to talk about labeling and REMS as we have yet to submit an NDA for the program. But based on our dialogue with FDA and the sort of implicit realities of the fact that in these studies, while for research purposes, we kept everyone under observation for the full 8 hours. If any patients, we didn't know going in the study, of course, but if any patients had progressed beyond that 8 hours, this checklist was what was going to be used to determine their safety to subsequently end monitoring during the dosing session. So there's some sort of implicit reality that this end of session checklist is appropriate to inform the end of that monitoring. As a result, we've had a very specific conversation with FDA over time, all in service of trying to reach a goal that appropriately monitors patients but doesn't place an undue burden on patients or providers. Because we're talking about an extended intervention, of course, a patient who has a return to normality of perception by hour five, it's hard to see what the value in holding that patient under observation for many more hours would be. So we think the approach and the very specific and intentional conversations we've had with FDA over the course of the development program, have chartered a path to bring this into the regulatory discussions at the NDA stage. Of course, as we see with products like SPRAVATO out in the market today, using a similar framework to both setting a minimum standard for when patients need to be in the clinic under observation, but then using a checklist such as this to determine when they can then safely leave observation. Thanks. We'll take our next question from David Amsellem with Piper Sandler. Please go ahead and ask your question. Okay. Thanks. Can you hear me? Yes. Yes. Okay. Sorry about that. I have a commercialization question here, which is, as you think about the magnitude of effect, the rapidity of effect, and the fact that this is a single treatment on a single day, do you envision significant usage potentially as a frontline or second-line option? I realize that might be putting the cart before the horse here. Obviously, you still got to get it approved. There's additional data readouts. As you think about what you've shown this morning, how do you see the usage paradigm, particularly in patients that have not had significant antidepressant exposure playing out? Thank you. Yeah. Thanks so much for the question, David. Yeah, thank you. At a high level, and then I'll turn it over to Matt to maybe add some detail. At a high level, of course, our expectation is that early adoption would be in patients who have been failed by two or more prior therapies. We see this with virtually all new branded products in psychiatry and these indications. The intentional choice to go after the broad MDD and GAD labels, though, certainly opens up the possibility that over time, either as we build evidence or as the overall landscape changes and the recognition of the value that such a profound shift in patient expectations and improvement can lend, not only to those patients but to the overall system. We certainly think there are opportunities to broaden out where this treatment option could be available and try to have the broadest impact. Being siloed in a small corner of the market is certainly an early step. To really drive the full potential of what we see with DT120 in this field and the promise of these results, we do think quite expansively over time. In the near term, we're laser-focused on getting the launch right if we're able to get the product approved, and to making sure that in the early adopters, we see a really good uptake and good results out in the clinical world. Matt, turn it over to you to add any color there. I agree with all of that. I mean, the product profiles that we've tested in market research, this data exceeds what has been tested to date. There's more evidence to collect in market to understand how physicians and payers will react to it. The data does open the opportunity for earlier line treatment downstream, as Rob said, and we're very excited about that. All right. Thank you. We'll take our next question from Paul Matteis with Stifel. Please unmute your line and ask your question. Hey, can you guys hear me? Absolutely. Hey, Paul. Awesome. Hey, Rob. Hey, congratulations on the data, yeah, thanks a lot for taking my question. Absolutely. Thank you. As it relates to your guys' long-term retreatment data, I thought that was super interesting. Can you remind us how you're thinking about what constitutes a long-term exposure for your FDA retreatment database? Do patients need to be retreated a certain number of times per year to count as like an ICH Guidelines one-year exposure? Maybe more broadly, talk about just like the filing scenarios here and your level of conviction that one MDD study could be enough, or is that still sort of an open question and all dependent on the GAD readouts? Thank you. Yeah. Thanks so much for the questions, Paul. I'll take the second question first and then turn it over to Dan to talk about retreatment and safety. In our interactions with FDA. I just want to take a moment. We couldn't be here without the thoughtful partnership of FDA and the Division of Psychiatry. They have really, over the course of the 8-plus years that I've been working in this field, been great partners in all of this and been really data-driven and thoughtful in their approach. Of course, with drugs like this, the complexity of dynamics like retreatment and safety are somewhat unique from a regulatory standpoint. You need a regulator who is both thoughtful and exercises their good clinical judgment and discretion throughout. Going into this readout, over the course of the last several months, I think we've had several conversations with investors and the broader world about that potential. Certainly, even by long-established regulatory and evidentiary standards for approvals of products, there is a pathway that has existed for one-study approvals when there's strongly compelling evidence. Of course, our intent with such evidence is to go have a conversation with FDA, and they've, again, been very engaged with all of this dialogue over the course of both our GAD and MDD programs. We absolutely intend to go have that conversation with FDA and certainly believe we'll have a receptive and engaged audience and partner in those discussions. We absolutely hold ourselves to the highest standards of generating evidence. When there is such a profound need and the results are so compelling. If today's results aren't compelling, I'm not sure what would be. We certainly see and want to pursue every opportunity to accelerate access for patients because there is such an enormous need, and based on the data we have in hand to date, there seems to be a really unique opportunity to benefit those patients. The same will apply in Dan's discussion, I'm sure of the ICH requirements, but I'll turn it over to him to comment there. Yeah. Without reiterating too much of what Rob said about FDA as an incredibly collaborative regulator in this enterprise. I guess I can make a general comment about long-term exposure, which is that the designs of our study, in this case and our other phase III studies and, of course, our phase II study, are all very intentional and meant to meet multiple goals. One of those goals is thinking about what does a year of exposure mean when you have a drug that is fundamentally unique in psychiatry, in that exposures are spaced out, intermittent, and likely triggered by need, by clinical symptoms. The reason that we have this year-long study with about as close to real-world opportunities for open label treatment as you can get in a clinical study like that is because that gets to as close as you can get to what a year of exposure to the drug should look like and will look like in the real world. In our discussions with FDA, we've obviously addressed exactly this question: What does a year of exposure look like to a drug that is intermittently dosed based on clinical need? What we've come to is the studies that we've designed, where folks get the opportunity for exposure should they need it over the course of the year. We're confident that these designs bring us toward a safety database that represents real-world likely exposures and generates great evidence for the safety of the drug in that paradigm. Thanks, guys. Thanks so much, Paul. Our next question comes from Gavin Clark-Gartner with Evercore ISI. Please unmute your line and ask your question. Hey, guys. Thanks for taking the question. I thought that the subset effect, the forest plot that you showed, showing a consistency of effect in various subgroups, especially the patients who had failed more prior antidepressants, was really interesting. I was curious if that consistency of effect was maintained out to the 12-week time point. Appreciate this is just the top-line results, curious if you had a chance to look at any other factors like length of depressive episode, patients with comorbid anxiety, or anything else like that. Thank you. Thanks so much, Gavin. We are still early in digesting the full data sets, of course. There will be, I think, some really interesting finding as we progress through that. The forest plots at week six and at week 12, as we've been able to analyze them at this point, really do just speak to the consistency of effect. As Dan alluded, the reality that we aren't seeing a particular group that is responsible for driving or not driving a treatment effect at this point. Certainly, some of the other features that we talked about, Dan alluded to the relative incidence of past exposure to psychedelics, something that's come under a regulatory discussion historically. There, too, we saw that those with past exposure to psychedelics didn't differ from those who had no past exposure to psychedelics in any sort of statistical way. What we're really finding is that where we have reliable subgroup analyses, and I say reliable because, of course, with small ends for a subgroup such as that one, you can get statistical wobble. We haven't seen anything yet that statistically rises to a level of explainability or that would explain those results, and that's true at week six and at week 12. I think to a larger point as well, when you have a magnitude of effect as large as what we've seen here in a study of this size, it's really unlikely that you're going to find any subgroup that was somehow the fundamental driver of that. A magnitude of mean effect of this size has to be a population effect. We're really confident that this outcome represents our ability to move this scale across the population of MDD patients that generalizes out into the MDD patients seeking care in the real world. Great. Congrats on the results, guys. Thanks, Gavin. Our next question comes from Francois Brisebois with LifeSci Capital LLC. Please go ahead. Hey, guys. Can you hear me okay? Yeah. Hi, Francois. Oh, hey. Okay, great. I was just wondering about that five to eight-hour window to get out. Was there something there that you've seen with maybe the patients, the stratification a little bit? Is it like the more severe patients take longer? If you can touch on maybe the impact of the ODT formulation to fit in that window of 100% of patients getting out at eight weeks. If you could just touch on also the bar going forward for GAD. Does that impact anything? We see the powering going forward for five. Any thoughts there for the GAD readouts and expectations on that side? Yeah. Thanks so much, Francois. I'll turn the first question on the sort of subgroups in the session over to Dan. Yeah. It's a great question, Francois. Something we're obviously very interested in because as we move through this process and towards submission and, if successful, ultimately into the clinic, of course, we'd like to provide as much a priori guidance to treaters about what they can reasonably expect, both in the session and after the session, from an efficacy standpoint. A lot like the previous question where we look at subgroups and try to make predictions. At this point, nothing stands out that allows for this sort of a priori prediction of session length. Of course, as we speak, we're gathering more and more session data, and we'll continue to investigate every angle there to try to track down any features that might be predictive of really anything about what happens with folks when they get the drug. We're thrilled with the performance of the ODT formulation. This oral disintegrating tablet has a predictable onset and clearly a predictable resolution of symptoms. Notably, from the AE profile, and I didn't say this before, but I could have, the gastrointestinal AEs are markedly reduced versus the powder and capsule formulation we used in phase II. Across the board, we're really excited about the ODT formulation. Of course, we're also using this new checklist that we devised for the phase III studies after the phase II. We've kind of got two variables that are changing session time from our previous experience. Attributing a change to one or the other would always be a bit tricky. Again, like I said, we're going to keep looking at every feature we can that might offer predictive value to treaters who ultimately use this in the world if we're successful. I'll just add briefly that both of those changes were in service of what we've done from the beginning of this program, which is to start with the end in mind, to really think about the impact we want to have and how we can get this product out to patients in the most impactful way. The ODT formulation, the steps, the incremental changes, and the data-driven approach to inform both the dose selection, the dosage form, the way we monitor, and the way we collect those data to really granularly assess and granularly describe exactly what's happening is incredibly important. I think it's important for the entire field to be able to appropriately make arguments and make data-driven, data-informed decisions and present those decisions and arguments to FDA so that we can have something that's grounded in science, something that's grounded in the data and what can be safely done. We absolutely are committed to patient safety while trying to maximize the opportunity out in the world. I think you asked about the bar in GAD, too, Francois. Thanks for that. Of course, we're just overwhelmed with excitement by the data today. We've seen quite exciting historical data from our phase II study in GAD as well. We continue to have really strong conviction. The GAD studies, as we reported out from the sample size re-estimation, are quite highly powered. Really our desire is to have positive studies that enable us to chart the path forward and to move forward with regulatory submission. We need positive studies is really the bar. Of course, what we've said previously is that we think something that's four points or better really stands out. In GAD, in the context of a disorder where there has not been an approval since 2007, almost 20 years, we think that compelling evidence really will stand out above that four-point bar. We're excited to get to those readouts for both VOYAGE and PANORAMA in Q3. Thank you very much. Congratulations. Thanks, Francois. Our next question comes from Brian Abrahams with RBC Capital Markets. Please unmute your line and ask your question. Hey, guys. Congratulations on the data. Just given the magnitude of effect you're seeing here, I'm curious, do you plan to apply for breakthrough status? What the implications of that might be in terms of regulatory interactions, and if you are able to get an expedited path across both indications, anything beyond the additional phase III readouts in GAD that would potentially be gating for commercial launch and scale up here? Thanks. Yeah. Thanks so much for the question, Brian. We tend to not talk about sort of speculative things out in the future in terms of our regulatory engagements. As both Dan Karlin and I said, we have an incredible respect for and partnership with FDA and Dr. Farchione in Division of Psychiatry, and have had such a constructive dialogue. We certainly always pursue every opportunity to chart an efficient path to bring this product to market, as long as we're not introducing undue risk or lowering any sort of standard for the program. We're highly committed to doing this the right way, as efficiently and as quickly as possible. We're going to continue to have that dialogue in a number of venues, a number of ways, both through meetings and through the various submissions that are available to us with FDA. As that progresses and as we have clarity on the outcomes of those discussions, we'll of course, be sharing that more broadly. In terms of what else comes after that, if we're in a fortunate position to get an approval for this product, building an incredible team led by Matt here, in a commercial organization that will stand our test of excellence, just like our clinical, regulatory, and whole organization has over the past number of years. To bring in that leadership, to bring in those who have a ton of experience navigating complex launches, programs with REMS, controlled substances in psychiatry, we really think we're at the forefront of this field and are going to continue building in that direction. As always, try to set ourselves apart and set a new standard for what everyone should be expecting, both from this field and from psychiatry at large. Understood. Well, thanks again, congrats again. I know it's been a long journey, so really great to see the outcome. Great. Our next question comes from Sumant Kulkarni with Canaccord Genuity. Please unmute your line and ask your question. Good morning. It's nice to see the data. Thanks for taking our question. Clearly, it's not typical to see the placebo-adjusted MADRS score change you saw with DT120 in a phase III for depression. When you combine that with the response and remission rates you saw and the longer-term part V data, what might that mean for the number of doses of DT120 that might be required over the course of a year for depression and for potential pricing, given the solid durability you see here, especially relative to the number of times a patient might have to go into the clinic for SPRAVATO, as an example? Thanks so much, Sumant. The staggering efficacy we saw in Emerge study really is not normal. I think that something that really cannot be overstated is just how unique this is. Of course, while any sort of cross-study comparisons always have their limitations, right? Each study has a different design and different sites. Will, of course, recruit different patients and have different things like placebo responses that can influence outcomes. Across the board, when we look at placebo-adjusted changes in this study, we see efficacy that stands out. That means things like a 9.8-point MADRS separation at week four. You stack that up against 6.8 points for SPRAVATO at their week four time point in their monotherapy study for TRD. I mean, that's the difference of one session with an average duration of 5.8 hours versus 32 hours in the clinic across 16 sessions for intranasal ketamine. A quite different and distinct, more profound underlying change is what we hear qualitatively from the patients in these studies. Again, we have a very high bar for how we think not only of the standards of our data, but what we expect from this program. In any context, put up against any data that we have seen in depression to date, this study and this drug continues to exceed those expectations and really stand apart. We think that there is an enormous degree of opportunity here and an enormous degree of enthusiasm, of course, from us, but also broadly from the field of psychiatry and from the patients we want to treat. Our next question comes from Jay Olson with Oppenheimer. Please unmute your line and ask your question. Oh, hey. Congratulations on these landmark results. This is great news for patients and their families. Since you saw no increase in suicidal ideation, do you think that would be an important differentiator for DT120, especially for moving into earlier lines of treatment in terms of not requiring the patient to fail SSRI treatments to have box warnings for suicidality? Thank you. Yeah. Thanks so much for the question, Jay. I mean, what we see is that there tend to be a feature of depression, and that's true whether it be labels for MDD or TRD or bipolar depression, all tend to carry that box warning. I think that it's a reasonable expectation that most products will continue to, even products like SPRAVATO that are approved to treat suicidal ideation and behavior in MDD carry that box warning. It is a feature of MDD and something that prescribers and patients should be made aware of. The really encouraging thing that we see, we don't want to take a sort of deductive view of this from not seeing a suicidality signal. What, of course, enters the risk for suicidality is when patients have an early activation but do not have improvement in mood, and to see such profound acute effect. As Dan described, category shifts on the CGIS over the course of the first week. A 14-point placebo-adjusted change at week one on the MADRS. To get such a rapid response, I mean, that's the thing that's driving such enormous adoption of things like SPRAVATO out in the world, is the fact that patients can come in and quickly thereafter leave better. The change here is that they also stay better. That we're able to show that they not only acutely improve on average, but that change is durable for at least 12 weeks thereafter. We're going to be absolutely focused on continuing to craft that narrative and share those data and make sure that that translates out into the world. I don't know that we would point just to the lack of suicidality risk as a single differentiator. Great. Congrats again. Thanks for taking the question. Thank you. Our next question comes from Christopher Chen with Baird. Please unmute your line and ask your question. Good morning. Congrats on the data. Thanks for taking my question. Just going ahead and looking ahead to ASCEND, just a quick question. If there was any color on enrollment updates there, and maybe thoughts on possibly how this data might spur enrollment for ASCEND. Thank you. Yeah. Thanks so much, Chris. We don't have an update that we're going to be sharing today on ASCEND enrollment. We have seen a high degree of engagement from our sites, and that's true across the EMERGE and ASCEND studies, the VOYAGE and the PANORAMA studies, and every study we've conducted. What we hear, again, qualitatively, quite often, is that when sites are running studies of daily drugs and when they're running studies with DT120, again, these are anecdotes, so take them with the appropriate grain of salt. These sites tell us that patients really don't want to be taking daily drugs. That they tend to have a preference for going into studies where they have an opportunity to take a drug, to be in a clinic for a day, and then potentially come out quite a bit better and impacted over the course of several months. We expect that enrollment and the momentum we have across our clinical programs to just continue. Of course, we're incredibly excited to not only get to the ASCEND readout next year, but to get in very near term here to our two pivotal readouts in GAD. Great. Thank you. That concludes the allotted time for the Q&A session. I will now hand back to management for closing remarks. Thank you, everyone, for being here today. Before we close, I just want to say a brief thank you to everyone who's been involved in this process. To be on the cusp of delivering a new product like this is something that's really special to be a part of, and especially a part of no matter whether you're inside of the company or whether you're working with us in any capacity or supporting this in any capacity. I think to zoom out for just a second, while, of course, we're here to discuss the study and our organization and the progress we've been making, we have a real opportunity to actually change the landscape for these patients. We've been heading in the wrong direction for quite a while in the treatment of mental health disorders. To have that opportunity, to have an organization that can deliver on that vision is something that we certainly feel very proud to be a part of and a high degree of responsibility to do appropriately and to do well. Again, whether you're sitting on the call here or involved with us directly in any day-to-day sort of operational role, I want to thank you for being a part of this and for making this possible and for believing in that future that we do, that we can really make a profound change in psychiatry and a profound change for these patients. We're very excited about the months and years ahead of us, and we'll look forward to sharing in those successes, hopefully, over the course. Thank you. This concludes today's conference call. You may now disconnect.