Hello, and welcome to the Definium Therapeutics Phase III Voyage top line Results Call. We ask that you please hold all questions until the end of the prepared remarks, at which time you'll 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. Thank you, operator. Hello, everyone, and thank you for joining us this morning. I'm Rob Barrow, Chief Executive Officer of Definium Therapeutics, and I'm joined today by our Chief Medical Officer, Dr. Dan Karlin, and our Chief Financial Officer, Brandi Roberts. We could not be more excited to be here with you this morning to share the unprecedented top-line results from Voyage, our first pivotal study of DT120 ODT in generalized anxiety disorder, or GAD. Before we get started, please note that on today's call, we'll be making certain forward-looking statements. We encourage you to review our SEC filings for a discussion of the risks and uncertainties associated with these statements, including the risks described in our most recent annual and quarterly reports. When we presented our Emerge results in June, I noted how rare it is to have an opportunity to share truly transformational data. That is even more true today when we have the privilege of sharing such findings for a second time in a row. As with our MDD results, we believe the findings being presented today have the potential to redefine what patients can expect from the treatment of GAD and position DT120 as a potentially best-in-class product across two of the biggest and most impactful indications in psychiatry. I'd also like to take a moment to thank our study participants, investigators, partners, and our incredible team at Definium for making all this possible. We are deeply appreciative and humbled by your commitment, your trust, and your belief in our vision. 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 a belief that profound change in psychiatry is truly possible. We set a high standard for DT120 to demonstrate that a single supervised dose can deliver rapid, robust, and durable efficacy and offer new hope to the tens of millions of people living with depression, anxiety, and other mental health disorders. We've always believed there's a particular need for innovation in anxiety, and we've remained steadfast in prioritizing GAD as a lead indication for DT120. GAD places an enormous burden on patients, families, and society, impairing daily function, productivity, and quality of life. That burden has grown dramatically. Prevalence has increased from roughly 3% in the early 2000s to approximately 10% today. At the same time, we've entered an era of far greater awareness and openness around anxiety and its impact on people's lives. But our ability to treat it simply hasn't kept pace. There hasn't been a new drug approved for GAD since 2007, and that's not for lack of trying. Over that period, roughly a dozen drug candidates spanning numerous mechanisms have advanced into late-stage development. Nearly all have failed, with most unable to demonstrate any meaningful improvement over placebo. That long period without success has also left the field without a modern benchmark for what truly compelling efficacy in GAD looks like. We believe the unprecedented Voyage results we're sharing today change that. They represent the promise of real progress for patients with GAD and further reinforce the potential of DT120 to help usher in a new era of psychiatric care. Voyage marks our second pivotal readout for DT120 this year and our first pivotal readout in GAD. As with our Emerge readout, Voyage met the primary and all key secondary endpoints with a high degree of statistical significance. Seeing consistent positive outcomes across two large phase III studies and two adjacent comorbid and highly prevalent psychiatric disorders further strengthens our confidence in the potential of DT120 and the broader opportunity ahead of us. To briefly summarize some of the key points, the primary endpoint demonstrated a 5.4-point placebo-adjusted improvement on the HAM-A at week 12, corresponding with an effect size of 0.81 and a P value of less than 0.0001. To our knowledge, this is both the largest nominal change and largest standardized effect size ever observed in a pivotal study in GAD. This efficacy was also rapid, with a 7.7-point placebo-adjusted improvement on the HAM-A at week one and a 0.8-point placebo-adjusted improvement on the CGIS at day two. DT120 was well-tolerated with no new safety signals identified, including no suicidality signal. We continue to observe an efficient and predictable dynamic of treatment sessions with an average time to clearing the structured end of session checklist of 6.4 hours and over 90% of participants clearing by hour eight. The strength of the DT120 program as a whole is anchored in consistency. DT120 has demonstrated a large and consistent effect size with a Cohen's d of over 0.8 in each study. Using the standardized effect size is especially useful in looking across studies, as changes in study design, population, baseline characteristics, and other study dynamics can impact nominal scores and make comparisons of nominal scores difficult. The fact that this extraordinary effect size has now been shown across three studies and two indications gives us a high degree of confidence in the robustness of the efficacy and continues to build the case for a potential multi-indication practice-changing profile. And finally, to put all this in context with the broader treatment landscape, DT120 has now shown in two studies in GAD an effect size of 0.81, and that is more than double the standard of care. To reiterate that, in a disorder with high prevalence, high burden, high unmet need, and no innovation in decades, a single dose of DT120 has shown a rapid and durable effect with a magnitude that is more than twice as large as the drugs approved today. With that, I'll turn the call over to Dan, who will walk through the study results in greater detail. Hey, thanks, Rob. Today is a special day. As a psychiatrist who has treated many patients with GAD, I have seen firsthand how difficult it is to help these folks find relief from the complex interplay among the emotional, cognitive, and somatic experiences of the illness. In our studies, these are measured using standardized assessments like the HAM-A, but in people's lives, they produce a nearly constant onslaught of distressing internal experiences. Medications available today may tamp down one aspect of someone's experience of anxiety, but often leave the others untouched. What we've seen in phase II and now in Voyage is that DT120 provides a different kind of relief in those who benefit from it, a relief that isn't bound to one domain of the illness. I'm excited to share further specifics of the Voyage results with you. As Rob highlighted, the study demonstrated rapid, robust, and durable improvements in anxiety, along with a favorable tolerability profile and efficient treatment session dynamics. Let me begin with the study design. Voyage is comprised of two parts. Part A, which is a 12-week randomized, double-blind, placebo-controlled period, and part B, which is a 40-week extension period with opportunities for open-label treatment. Participants were tapered off background antidepressant and anxiolytic medications prior to enrollment, and no psychotherapeutic intervention was provided as a part of the study. In part A, participants received a single dose of DT120, 100 mcg or placebo, and were followed for 12 weeks. The primary endpoint in the study was changed from baseline in HAM-A total score at week 12, assessed by independent central raters who were blinded to treatment assignment and visit number. In part B, participants continued to be followed for an additional 40 weeks and completed regular, blinded, centrally rated efficacy assessments for a total of 52 weeks of blinded efficacy assessments. Each time a participant meets the study's pre-specified criteria for retreatment, they become eligible for an open-label dose of DT120 for a total of up to four open-label doses. The retreatment threshold in part B is a HAM-A total score of 16 or greater, which corresponds to the cutoff for moderate illness and is characterized by a meaningful increase in disease burden, functional impairment, and disability. From the outset, we picked this cutoff as the target for treatment because we thought it was both achievable and meaningful to patients. A total of 214 participants were randomized in the study, with 107 participants in each arm. Approximately 90% of randomized participants completed part A. The demographics of participants enrolled in Voyage were generally balanced between treatment groups and representative of GAD patients commonly encountered in clinical practice. Participants entered the study with a high degree of disease severity, as reflected by baseline HAM-A and CGIS scores of 27.9 and 4.6 across the groups. These values place participants firmly within the severe range of anxiety. We also observed past psychedelic exposure consistent with the background range of use in the population we would expect based on epidemiological estimates, with 21% reporting any prior psychedelic use and 9% reporting prior LSD use. Another way to understand the enrolled population is to look at the distribution of disease characteristics at baseline. Three-quarters of participants were characterized as severe on the HAM-A, with a score of 24 or higher, and the remaining one-quarter categorized as moderate with a HAM-A of 20, the minimum for study enrollment to 23. Despite a limited number of treatment options, we observed a population with characteristic prior treatment experience. 36% of participants reported receiving two or more prior GAD pharmacotherapies. One particularly notable aspect of the experience of GAD for these participants is the time since diagnosis and time since symptom onset. On average, participants in the study reported experiencing GAD symptoms for approximately 24 years at the time of enrollment, and on average, received their GAD diagnosis about 12 years prior to enrollment. This speaks to both the long delays in diagnosing GAD and the reality that GAD is a chronic, lifelong condition that leaves the folks who suffer from it to do so without diagnosis or explanation for many years, and in cases like our enrolled population, to continue to not find relief even long after diagnosis. Between our MDD program and our GAD program, we have endeavored to recruit populations that are maximally representative so that we can make reliable and reproducible assessments of DT120's ability to treat the disease of interest, both with and without comorbidity. On the HAM-A, which was the study's primary outcome measure, DT120 demonstrated rapid, robust, and durable efficacy. At every measured time point, DT120 statistically and clinically exceeded placebo on the HAM-A total score, demonstrating a consistent treatment effect throughout the study. In fact, at each time point, the P value was less than 0.0001. There are several dimensions we consider when evaluating a treatment profile. First is robustness. At the primary endpoint measured at week 12, DT120 demonstrated a mean improvement of 11.6 points and a placebo-adjusted change of 5.4 points. Rapidity is particularly important for patients with GAD. By week one, the first HAM-A efficacy assessment after treatment, patients receiving DT120 showed a mean improvement of 11.9 points from baseline, corresponding to a placebo-adjusted change of 7.7 points. This early separation from placebo was maintained across subsequent assessments. Taken together, the rapid onset of action, robust magnitude of improvement, and durable benefit observed over 12 weeks provide strong evidence of a meaningful and sustained treatment effect after a single administration of DT120 in patients with GAD. A secondary measure of disease severity is the CGIS, and here we see that the CGIS tells essentially the same story as the HAM-A. Key secondary endpoints shown here are change from baseline in CGIS score at week 12 and early improvement measured at day two. Notably, these instruments, the CGIS and the HAM-A, use different mechanisms to assess the underlying illness and are conducted by different raters. The HAM-A is assessed by independent centralized rater, while the CGIS is a local site-based clinician-rated measure. The consistency across these independent measures gives us tremendous confidence that the treatment effect that we are able to measure represents real, meaningful clinical improvement in the study participants. Another way of looking at the HAM-A data is based on fixed thresholds, remission, and mild. We can also look at relative response rates. At week 12, 14% of participants receiving DT120 were in clinical remission, compared with only 4% of those receiving placebo, with a P value of less than 0.05. 51% of participants in the DT120 group reached mild or better status, compared with just 23% of those receiving placebo, with a P value of less than 0.0001. 43% of participants receiving DT120 met the response criterion, compared with 16% of those receiving placebo, with a P value of less than 0.0001. These response and remission outcomes further support the clinical relevance and robustness of the treatment effect observed with DT120. We also conducted subgroup analyses to better understand whether the treatment effect was consistent across different patient populations and baseline characteristics. We evaluated factors such as time since diagnosis, prior GAD medication exposure, and sex, along with a number of other baseline measures. Across each of these analyses, the treatment effect was reliably similar. Importantly, this included patients who had been failed by two or more prior GAD treatments, a population with substantial unmet need and often more limited treatment options. The consistency of these results across the subgroups strengthens our confidence that the benefits observed in Voyage are broadly applicable across the GAD population and are not being driven by any single patient group. Turning to safety, DT120 was generally well-tolerated, and the adverse event profile was consistent with the known pharmacology of DT120 and with prior clinical experience. DT120 showed a favorable tolerability profile with all adverse events mild to moderate in severity and most treatment-emergent adverse events occurring and resolving on dosing day. There were no serious adverse events in the DT120 arm, no suicidal or self-injurious behavior, and no indication of drug-related suicide signal or suicide-related risk based on C-SSRS assessments. In the DT120 arm, 61% of AEs were mild and 38% were moderate. One severe AE of diverticulitis was reported in the placebo arm. There were three treatment-emergent serious adverse events in the placebo arm, one adverse event leading to discontinuation in the drug arm, and no adverse events leading to death. The discontinuation was related to a new-onset depressive episode approximately six weeks after dosing in a patient with comorbid recurrent MDD. Taking a look at the most common treatment-emergent adverse events, those with an incidence of at least 10%. The most frequently reported events were the expected transient perceptual, affective, cognitive, and behavioral changes occurring primarily on dosing day. These events were mild to moderate, occurred on dosing day, and resolved by the conclusion of the dosing session. Rob mentioned this earlier, and we believe the treatment session dynamics remain one of the most important aspects of the overall profile of DT120. The DT120 session is well-matched to the needs of GAD patients, with a combination of session duration and depth of experience that continues to produce efficacy outcomes like the ones we've been able to share with you today. We use a structured end-of-session checklist to assess readiness to safely leave the treatment setting. The average time for clearance on the checklist was 6.4 hours, with more than half of participants clearing at hour six and 92% clearing by hour eight. When we look at all of the known phase III DT120 dosing sessions, we see a remarkably predictable duration with the vast majority lasting between five and eight hours. We believe this translates very cleanly into clinical practice, where the end-of-session checklist can be easily implemented to inform medical decision-making and the clinical staff involved in supervising sessions. Now we turn to part B, the 40-week extension phase. As a reminder, participants are eligible to receive up to four open-label treatments with DT120 based on disease severity of moderate or worse, as assessed by the centrally rated HAM-A. The purpose of this phase is to better understand long-term durability from part A, subsequent treatment patterns, response to retreatment, and their durability over the full year of observation and dosing opportunities. At the time of the interim analysis, 87 participants assigned to DT120 and 90 participants assigned to placebo had entered part B. Today's discussion focuses on data through week 28, where enough participants have been evaluated to provide a meaningful analysis. The demographics and baseline characteristics of participants entering part B were generally consistent with the broader part A population. As expected, symptom severity of part B entry reflected the treatment effects observed during part A. As anticipated, multiple treatment trajectories emerged, with participants receiving intermittent open-label treatment based on symptom recurrence and retreatment eligibility. The data show a distribution of participants receiving zero to three open-label treatments through week 28. These early patterns provide an encouraging first look at how DT120 may be used in a real-world treatment setting. Longitudinal HAM-A scores moving from part A into part B continue to show both the ongoing durability from the initial dose of DT120 in the active arm and the incremental benefit from open-label treatments. Participants originally assigned to placebo begin to converge toward those who received DT120 in part A after receiving open-label treatment. These results increase our confidence in the durability and retreatment paradigm for DT120 and provide early support for how intermittent dosing could sustain improvement over time. As with part A, we can look at response and remission over time in part B. What we see is that across each of these measures, patients continue to benefit with subsequent treatment administrations. Response and remission rates improve through week 28, demonstrating sustained disease control over time. The consistency of these findings across multiple clinically meaningful endpoints and safety measures gives us enormous confidence in the potential for DT120 to safely deliver durable efficacy with intermittent symptom-triggered retreatment in a variety of real-world clinical settings. With that, I'll turn the call back over to Rob. Thanks much, Dan. As I said at the outset, our goal at Definium is to enable a new treatment paradigm that can profoundly reshape clinical practice in psychiatry. We believe the landmark results shared today are another important step in pursuit of that goal. With the unprecedented results we have delivered in MDD and GAD, we continue to build what we believe is one of the strongest clinical data packages in psychiatry. We are moving with a high degree of urgency to pursue a potential NDA submission for DT120 ODT, and we approach our final pivotal readout of 2026 with more momentum than ever. Looking ahead, we anticipate the top-line readout from Panorama next month. We continue to advance Ascend and MDD toward a top-line readout in 2027. We are progressing plans to initiate Haven in PTSD in 2027. The need across GAD and MDD remains enormous. Today, an estimated 50 million adults in the U.S. are affected by GAD or MDD, with approximately 26 million diagnosed, 13 million receiving pharmacotherapy, and more than 4 million having been failed by two or more treatments. We believe this represents a significant opportunity to bring a differentiated treatment to patients who continue to need better solutions. Even modest uptake in the addressable population has the potential to impact tens of thousands of patients and create substantial value. Importantly, we view that initial scale as the starting point rather than the ceiling, with a long-term opportunity that could meaningfully expand as we continue to generate evidence, broaden access, and reach additional patients across these large and underserved markets. We see two distinct value drivers ahead of us: our continued commitment to excellence in clinical and regulatory execution 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 psychiatric powerhouse that can reset expectations for what patients and providers can expect from care. Before we go to Q&A, I want to say a special thanks again to our incredible team at Definium. We've built an organization of exceptional people who are deeply passionate about our mission and the patients we serve. None of this would be possible without your unwavering dedication and tireless effort. It is an honor and a privilege to work alongside each and every one of you every day, and I cannot wait to see what the future holds for all of us. With that, we will open up the Q&A. 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'll 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. Our first question comes from Andrew Tsai with Jefferies. Please unmute your line and ask your question. Hey, good morning. Congratulations again on another robust data set. My question is basically around now that you have three profound game-changing phase II/III data sets in MDD, GAD, can you maybe talk briefly about what your FDA interactions actually have been like after the MDD data set in June? Whether there is any inclination the agency might be supportive to a combined filing in MDD and GAD, actually. Secondly, for MDD, could we expect you to seek a breakthrough designation? You already have one in GAD. I figure maybe a breakthrough can help the MDD timelines as well, because I think you're waiting for the base case MDD second phase III to read out in 2027. Thank you. Yeah. Thanks so much for the question, Andrew, for being here this morning. We've had an incredible dialogue, and I think it's worth taking a minute to just acknowledge the division of psychiatry at FDA. These drugs that we are working on, and the entire field is working on, have been sitting on the shelf for 60 years, almost 50 years. The willingness to look at science objectively and lean in and understand the complexities and navigate those complexities with us is something that isn't required of any agency, and FDA has really stepped up to meet that mark. It's really encouraging, I think, for all of us and for the field of what lies ahead. In terms of interactions, we regularly are having formal and ongoing dialogue with FDA on a number of fronts on everything that goes to what's going to inform our NDA filing strategy. As we approached the Emerge data in MDD, we obviously were very much focused on that potential, and we've been working very hard over the course of this year to prepare ourselves for an NDA filing and draft a lot of the NDA, which we made incredible progress towards. With three data sets in phase III, if Panorama is positive, we certainly believe there is a compelling opportunity, a compelling reason, to consider filing and consider a path to getting both of these indications on the label. The effect sizes we have now consistently shown across three studies are outstripping everything that is approved today, and really, from what we've seen, everything that's in development. That puts us in a position where we can think broadly about the patient population that's in need here. With the strength of those results, we're still conducting a second study in MDD, but the added value of additional research, we already have a high degree of statistical significance and a belief in the effect across both of these indications. We continue the dialogue with FDA. We're going to continue having those meetings. We've had meetings since the Emerge results. We'll continue to have meetings in the months ahead as we approach and get closer to filing or potential filing for 120 in these indications. As far as a breakthrough therapy designation goes, we have had, again, a great dialogue and a great opportunity to really interact with the agency frequently under the GAD program. We're always exploring every opportunity to bolster that alignment, that collaboration with FDA, and to seek every way to expedite development and path to market. We are going to continue exploring all those options. Certainly, as any of that unfolds, we will continue to share updates as they go. Our next question comes from Marc Goodman with Leerink. You may now unmute your line and ask your question. Lizanne, on for Marc. Thank you for taking our question. I was just wondering if you could share some detail on what exactly is included in the end of session checklist, and if the FDA has given any feedback on how it may be used in clinical practice. Also, if it has evolved over time since it was used in the phase II study. Thank you so much. I will turn that one over to Dan here to comment. Thanks. Yeah. Thanks. It's an excellent question, and we obviously focus on this because we think it's incredibly important to provide tools to clinicians so that they can make informed medical decisions in the use of a product if approved. The phase II study used a different instrument that we devised because we hadn't had clinical experience using 120 in treatment of people with GAD at that time. In phase II, we looked at the entirety of the DSM-defined symptoms of hallucinogen intoxication to just try to understand what it looked like for folks between hours eight and 12 after treatment. We also used a 200 mcg dose in phase II, so we just really wanted to understand and characterize what the end of that experience looked like. Beginning in phase III and in our safety studies after the transition to the ODT product, we created the end of session checklist, which effectively looks at the domains required for capacity for decision making. It looks at people's alertness and orientation. It looks at the resolution of perceptual symptoms. It looks at their ability to safely navigate their environment and things like this. It's an eight-item scale, and throughout our use of it's been submitted alongside protocols for FDA review. We've gotten extensive FDA feedback. We've had back and forth with them on even the details down to the item level and the phrasing of those items as we've moved along. Because we use the checklist in our trials, despite having an eight-hour minimum, the requirement for end of session in the studies is eight hours plus checklist completion. What we take this to mean is that the checklist is adequate for determining people's ability to safely end their sessions. While we have no reason to think that an eight-hour minimum persists in the real world because that's a trial artifact, right? We need to have long enough sessions to ensure that we're not letting half of patients in part A leave at whatever that minimum is, and the others have to stay longer because they're not quite ready to leave. That would provide another source of unblinding and confounding in the study. Based on the checklist results that are showing the sorts of numbers we're seeing at five and six hours ready to leave, we fully expect that it will translate very cleanly into real-world clinical practice. Our next question comes from Gavin Clark-Gartner with Evercore ISI. Please unmute your line and ask your question. Hey, good morning. Great to see this data. Just for the second GAD phase III study, could you remind us what your expectations or maybe lack of expectations are for the 50 mcg control arm that's included there? Thanks. Yeah. Thanks so much, Gavin, and thanks for the question. Yeah. I think this is one of those dynamics. When we look at the field and research methodologies in the field, there historically have been a lot of different ideas out there, and a lot of those have fallen by the wayside. The concept of adding on additional controls and studies is a reasonable one, depending on the motivations for it. With the inclusion of an intermediate or a lower dose of drug, particularly here in what it's intended to do, it's trying to mitigate the connective tissue, let's say, between potential expectancy and biasing outcomes after the drug's administered. We continue to see that patients who are administered 100 mcg of DT120 can reliably guess that they received the active drug. I think it's just somewhat common sense here that people taking a high dose of any psychiatric drug, but a high dose of certainly a drug that profoundly alters affect and perception and things of that is going to be detectable. What we try to do is include the 50 mcg dose so that in the consent process, we can inform patients that just because they feel something on the day of dosing, they can't be sure that it's the active dose of drug. Because we've also seen in our phase II study that 50 mcg, while it produced no clinical separation, clinical activity over placebo, it was also very reliably detectable by the patients. The logic is just because you feel something, don't assume it's the real thing. The important part is that it doesn't have any impact on how we're assessing, analyzing, or interpreting the results of the study. I always probably too much rely on analogy of eyeglasses. If we were to do a study of patients with eyeglasses and gave some people half the prescription that they would see well with, and we gave other folks placebo and we gave other folks their correct prescription, it wouldn't negate anything if we found that people who get half the prescription can see a little bit better. The reality is that a drug that works regardless of what other doses of that drug do. We're not at all focused on that retrospectively as a sort of analytical outcome. It is purely an operational control and something that is designed to have prospective utility in the study. Our next question comes from Paul Matteis with Stifel. Please unmute your line and ask your question. Hey there, this is Emily on for Paul. Congratulations on the data. We were just wanting to think, as we look ahead to the commercial opportunity in GAD, what is the profile of these early adopters? Given that many of these patients are currently treated in primary care, what are the levers you guys can rely on to try and change referral patterns to get patients into these more interventional centers? Thank you. Yeah. Thanks so much, Emily. A thing that is part of our belief in the opportunity to have a profound impact for these patients is a recognition that if we go all the way back, psychiatry really started focused on anxiety symptoms. That is structurally where the focus was. It's where early pharmacotherapies were really focused in neurotic ailments. We had barbiturates. Obviously, benzodiazepines. Over time, the entire system shifted away from that. Perhaps in part because it's so difficult to actually show any improvement on. When we look at that reality and we think of what's possible, we don't look at the fact that a lot of anxiety patients are given SRIs in primary care and say, "Oh, well, then they're inaccessible to us." It's just an artifact of the reality that that's kind of all we have today. Without long-term benzodiazepine use, the class of drug that is really used are SRIs, and there's only a few of them approved in anxiety disorders. Certainly on a personal level, when we talk to anyone with anxiety, we don't hear them saying, "Well, I'd rather stay in primary care on the drugs that I've been taking," if they haven't been working for them. There's a real eagerness to have better options. I think even for those patients who aren't currently in treatment, the availability of something that is really actively effective for them could drive further seeking of care, right? If a patient doesn't have hope that they can get better by getting treatment, why go get treatment in the first place? That's really, I think, an opportunity initially to focus on those that are easily identifiable, that are already showing up and have comorbidities. Obviously, one of the things that is really cool with what we have seen so far in the data is that we seem to have an even more pronounced effect when looking at anxious depression or depressed anxious populations. Either of these studies, either direction we look. There is an enormous initial opportunity with millions of patients. But over time, we think that it grows even further. Turn it over to Dan to maybe comment a little bit further, too, just on patient profile. Yeah, for sure. I absolutely agree. What we have observed repeatedly in the epidemiology that exists and in the epidemiological work that we have done is that there is this huge population of folks who are either undiagnosed or undertreated. As you note, that absolutely happens in primary care settings. Our early patient profiles, most likely to get the drug soon after launch, are folks who are not exactly that population. While, as Rob says, we will work on the levers that allow folks to advance through the care system such that they ultimately have access to the drug. But early on, the folks most likely to get our drug are people who have had these multiple drug trials, each of which has been in some way unsatisfactory, either inefficacious or excess side effect burden. Usually, it is a combination of the two. The side effect burden exceeds the benefit, and it is not worth it to stay on the drug for the patient, or they stay on it despite that because it offers some little relief. By the time folks have had these drug trials, they are almost always in the care of a psychiatric professional, either an advanced practice nurse or a psychiatrist. Because working with these late-line drugs is something that the primary care just generally does not do. It is those patients in particular, the ones with severe illness who have progressed through the system, who have ended up in the care of psychiatrists and APRNs, and where those prescribers are the very same people we talk to who say that they do not have the tools in their toolbox to be able to adequately address the suffering of those patients. At every level, those patients who are out in the world who have never been diagnosed, the patients in primary care who have been, and the patients who have been traveling through the system and are in late-stage use of drugs that may even be prescribed off-label. We think we have the ability to access each of them at various stages after we launch, if approved. Our next question comes from David Amsellem with Piper Sandler. You may now unmute your line and ask your question. Thank you. I had another question about commercial, clinical practice. How do you think treatment in practice is going to shake out between monotherapy of DT120 versus adjunctive therapy? In other words, patients staying on their background antidepressant or anxiolytic therapy. This is bearing in mind, of course, as you know, it's not easy to taper off of reuptake inhibitors, particularly dual reuptake inhibitors. How are you thinking about that, and do you expect that practitioners will lean more into keeping their patients on their background medications and just layering in DT120? Or do you see a paradigm where tapering is going to be more the norm? Thanks. Yeah. Thanks so much, David. I'll turn that one over to Dan to answer. It's an excellent question, David, and it's something we talk about a lot ourselves and with the clinical experts we engage with on a near-daily basis. There's a larger structure to how we've done things through our development program, which is to say that we've designed our trials to attempt to demonstrate the minimum conditions necessary for safe and effective use. That is not to push into specific practice patterns to the extent we're able. Consistent with the history of drugs that have been developed and successfully developed for anxiety and depression, we tested the drug as a monotherapy without associated psychotherapy, right? We stripped everything back and tried to show to the extent we were able, drug-only effect. It's not because we think that's the absolute most efficacious way or it's a perfectly safe way to use the drug. But we didn't necessarily push for the most efficacious thing we could do with combination therapies because of that desire to show the minimum necessary conditions for safe and effective use. That included taking people off background medication. In the real world, we expect that clinical practice will evolve over time and that individual clinical practice will dominate the day. While there will absolutely be clinicians and patients who decide together that they want to take whatever meds are in the background because they're not working adequately and stop them prior to treatment. We also intend to and continue to provide information that will allow clinicians to also make the choice with their patients to keep background meds in the picture until relief is sustained from DT120. So that aspect of clinical practice is something which we'll be very interested in. We'll continue to design studies that inform clinical practice, but we wouldn't consider our role to say whether an individual patient and provider dyad should make one choice or the other. Our next question comes from Brian Abrahams with RBC Capital Markets. Please unmute your line and ask your question. Hey, good morning. Thank you for taking my question, and congratulations on the data. With these data in hand, what do you think you need to show in Panorama, to support filing an approval? Do you think you need to hit statistical significance at 100 mcg? Then I'm curious if you could just remind us the alignment you have with the FDA, specifically on their recent guidance, and if you're maintaining some blind here for the full 12 months, at least for investigators and patients to fulfill that. Thanks. Yeah. Thanks so much for the question, Brian. I think especially given the results today and the consistency of the large effect size that we've seen, we feel quite confident going into these Panorama data in September. As always, we're going to be in a dialogue with FDA, with more data that's going to inform those discussions. We feel very good about the path forward. We feel that we've demonstrated time and again some profound efficacy that has rarely been seen in these indications. We feel like there's a clear path forward for this drug. In terms of guidance and alignment, over the course of the development program, the last little under five years, we've had an incredible dialogue with FDA, and that dialogue has moved towards alignment, we think, in terms of the overall program, the methodologies we use in our trials and all of that. It culminates in public-facing documents like the guidance. That guidance is reflective of an ongoing discussion that we've had over that entire development program. In terms of the specific commentary about a year of blinded assessment, it's exactly what we have in this study. The rating of symptoms in the study is blinded at all times. We use central raters who are unaware of treatment assignment or visit numbers. They don't know if it's a screening visit or someone who's at week 52 after receiving several doses of DT120. Obviously, with a year-long study and with the sort of urgency that we have to move this program forward, at different times in the studies, we now have locked part A of the study and unblinded Voyage and or excuse me, Voyage and Emerge. The reality there is that of the four arms of the quadruple blinding in these studies at various points in time, one of those can be removed. When a patient takes open label drug, of course, from that point forward in the study, they are no longer blinded to subsequent treatment status, but they still remain blinded to their initial treatment status. All that is to say, we feel very much aligned with FDA, with FDA's guidance, and through that constructive dialogue, have landed what we think is a very reasonable and thoughtful approach at demonstrating safety and effectiveness in these programs. Our next question comes from Ben Burnett with Wells Fargo. Please unmute your line and ask your question. Hey, thank you, and I will add my congratulations to the data. I want to ask just about the placebo response. It looked pretty low, and it looked like kind of nominal values for both drug and placebo were maybe a bit lower than was anticipated from the phase II. Just curious if you could comment on that and maybe also just contextualize some of the remission rates, relative to standard of care drugs and anxiety. Thank you. Yeah. Thanks so much, Ben. You are absolutely right. A thing that gets missed here, a lot of times when studies do not show significance, placebo gets blamed. Which may be the case, may not be the case. But the reality is, placebo effect is not a placebo effect, really. It is the effect of participating in a study, right? Placebo does not actually do anything, otherwise it would be a bad placebo. When we think of the, quote, "placebo effect," it is really something that is going to accrue to all arms that are participating in the same trial the same way. That is the case here, right? So in our phase II study, we obviously had a much larger placebo effect. There are reasons to believe that a study with five arms, with an 80% likelihood of getting a dose of drug, could demonstrate that. We still saw an effect size of 0.81 there. We have seen an effect size of 0.81 here. While placebo numbers certainly change, and interestingly, we saw a virtually flat line for the drug from week one to week 12 in terms of HAM-A scores in this study. Placebo scores change over time. That is really what drove any of the changes in separation between the two arms over the course of the 12 weeks in today's data. When we think of that, we do not look at placebo as a sort of isolated thing. It is just a fact that in a study where a single intervention is given, where patients are then followed for three months with no subsequent intervention, and patients have a 50% chance of getting drug, is likely that you are going to have somewhat of a lower placebo than we have seen in the past. Now, compared to other studies in the field, we are seeing actually a much larger placebo. Some of the pivotal studies in our field have shown 3 or so point placebo effect. Now we have a study where we have shown around 5 and a study where we have shown a little over 6 here. So we think that we are actually seeing a pretty robust placebo effect, and we are still exceeding that by a wide margin and a very large effect size. I guess in terms of contextualizing the remission and response rates, that is something that is also dramatically affected by this exact dynamic, right? Adding 10 points of a placebo response to both arms is going to make any fixed numerical cutoff, whether it be a percentage or a nominal cutoff, seem a lot larger. The fact is we're seeing much higher rates of remission, of response, and as Dan said, of attainment of mild or better symptoms, which I think is a really sort of most important real-world clinical target. We're seeing much more of that in the DT120 arm than we have with placebo. We're also seeing over the course of the 52 weeks that with subsequent treatment availability and subsequent treatments, patients continue to accrue, and we get more and more pickup approaching well in excess of 50% in that mild or better category. Our next question comes from François Brisebois with LifeSci Capital. Please unmute your line and ask your question. Hi, thanks for that question and congrats on the data here. I was just wondering, in terms of the end of session criteria list, is there something where obviously the language has been worked on and discussed with the FDA, but is there something about specific patients that are ready to leave earlier? Maybe if you can compare and contrast with an MDD patient that although they're pretty long episodes, but just the chronic nature of GAD versus MDD. Just trying to get a little more color on what would make someone be able to leave earlier than someone else. Thank you. Thanks. Thanks so much, Franç. I'll turn that one over to Dan. Yeah. Franç, that's a question that we have been really interested in trying to answer to. Like a lot of things in medicine and in psychiatry, trying to predict outcomes from a priori data, from baseline data, is something that everyone has tried to do for as long as we've been treating people in the field. While we would love to be able to tell you we know what predicts that there's some patient profile, some knowable thing that predicts precise session length, thus far, we really just haven't been able to identify anything. We noticed this about half-hour longer session duration in the GAD study than the MDD study. At some level, the best we can do so far is attribute that to anxiety, that folks are in the clinic. Even though they, in many cases, are feeling a lot better, in terms of their anxiety by the end of the session, they still know that they felt anxiety last time they were outside of the clinic. There's a tendency in anxiety disorders to engage in a degree of what's called anxious avoidance. The sense we got in talking to our sites, which we do an awful lot when we try to understand what's happening in these sessions, during the sessions, at the end of sessions. Sounds like in some cases, these data are likely pushed just a bit longer by patients saying, "I'd just like to be here a bit longer." That's okay. A big part of this is that the session dynamics are, to our mind, inexorably linked to the effects of the drug in terms of efficacy. There's a degree of personalization that is intrinsic to the treatment with these drugs. It's mostly internal personalization. A part of that is people having the time to both have the transient effects of the drug and to feel like they've gotten back to a place where they're ready to head back to their lives. We've encouraged sites to lean into that degree of comfort for folks as they come through the end of their sessions. That's the best we can tell you so far. We've got plenty of sessions left to measure, and we're going to keep measuring everything we can and looking for correlations. I'll add just one brief comment to that, which is, maybe two, which is that we have yet to meet or talk to one of these anxiety patients who says, "I've been living with anxiety for 20+ years. It's severe. I can't handle this, but I'm unwilling to stay in the clinic for an extra 30 minutes or so." It just doesn't happen. The efficacy we're seeing is to a degree where someone with a probably lifelong, certainly multi-decade effect can be in a room for a day and walk out the door having a reasonable expectation of profound effect. That may take some time, but that time is very well worth it. I think that translates, too, in the same conversations we have with the investigators in our studies, with providers out in the world. They see the need. They work in this field to try to make people better. If every once in a while someone has to stick around for an extra 30 minutes, I do not know about everyone on the phone, but we have certainly worked after hours before and have not had any problems doing that every once in a while when you need to. We are going to be continuing to try to understand these factors, to try to be able to best inform practice. But we are really, really encouraged by all that we are seeing and the realities of what this drug could offer. Our next question comes from Jay Olson with Oppenheimer. You may now unmute your line and ask your question. Oh, hey. Congratulations on these milestone results. On the HAM-A scale, did you see any particular symptomatic relief that especially stands out? We are curious about anything you could share on cognitive or fatigue-related symptoms. Based on this dramatic effect size in GAD, do you think DT120 may also provide benefits to patients with panic disorder? Thank you. Yeah. Thanks so much for the question, Jay. I will turn it over to Dan to talk about the symptoms and all he asked. One comment I will make really quickly is that, as Dan noted, the baseline MADRS score. One of the things that was really interesting to us looking across the phase II and phase III studies is that the baseline MADRS scores in this study were around 14. Now, we continue to try to isolate the anxiety features here. We know there is a huge degree of overlap between both the HAM-A and the MADRS. There is a huge degree of overlap between the diagnostic criteria and the experience of GAD and MDD. In studies for regulatory purposes, we have to try to really isolate those variables, so we do not get into the historical concerns around pseudo-specificity, and we feel like we have very much done that here. We had much lower baseline MADRS scores, about half of the MADRS scores at baseline. That translated into a lower baseline presentation of depressed mood, which is an important and very common feature in anxiety and on the HAM-A. We kind of removed a couple of points of baseline severity by getting to the correct isolated population, the part of the Venn diagram that doesn't overlap as much. In so doing, we also took away the ability to improve those depressed mood symptoms, which, given the Emerge data, we feel like is probably something that would have moved pretty meaningfully since we showed that effect in MDD in particular, and we've seen that effect really pronounced in past studies. That also is one of those things we think may contribute to the sort of nominal differences, both in baseline in terms of the overall scores and how they shift between studies and why, again, those nominal scores aren't the best comparator across studies or programs. Turn it over to Dan to comment on the other specific. Yeah, Jay, I think you picked up on a bit of my editorializing there about domains. Yes, I mean, remarkable thing here. The HAM-A, by virtue of trying to assess the full spectrum of the experience of GAD, is a multi-domain instrument in a way that, say, the MADRS isn't, which has made it a difficult thing to move. The disease GAD is hard to make better, and the instrument we use to measure it is also hard to move, which creates a dual challenge in studies for GAD. It's one of the reasons here we are, 20 years after the last FDA approval for a drug in GAD. It's a hard thing to do. One of the remarkable things we've noted already, and we haven't had these data a whole lot longer than you have now, but one of the things we've been able to do is take a look at item level analyses. We really just found it incredibly remarkable what we were able to move. We see items in the somatic scale moving and in the cognitive scale moving, certainly in the fatigue scale moving, and of course, the psychic anxiety scale. We didn't have a whole lot of room to move in depression, as Rob said, because we isolated out GAD as much as we could from folks who are depressed. But yeah, across the scale, we see movement in symptom domains, and that is remarkable in part because patients come in with sort of an individualized pattern on the HAM-A, where their particular experience of the disease is manifest in different areas of elevation. The fact that we see this movement across these different domains of this scale means that for each patient, we're treating their individual pattern back down toward this mild remission state. As far as panic goes, epidemiologically, there's about a 25% overlap between panic and GAD. But in the treatment-seeking population, consistent with what we saw in these data, there are a lot of people out there who are not treatment-seeking despite having GAD. In the treatment-seeking population, that overlap can get up to be, like, 50%. Panic can often precede the development of GAD. There's some pattern-based reasons for that. While we wouldn't want to go outside of where we've tested the drug and make any claims there, just that known comorbidity and the ability to reduce anxiety in comorbid patients would suggest that for someone whose baseline anxiety starts high, being able to move them down ought to have an ameliorating effect on the frequency and intensity of their panic disorder. It's a great hypothesis, great direction to look, and of course, we're interested in all of the disorders that tend to accompany GAD and MDD. Our next question comes from Sumant Kulkarni with Canaccord Genuity. Please unmute your line and ask your question. Hi. This is Elias on for Sumant. Thank you for taking our question, and congrats on the data. One question about the part B portion of your trial. Were patients allowed to go back onto their background therapies? If they were, what proportion of patients selected to do so? Could this have any implications on a potential REMS program? Thank you. Yeah. Thanks so much for the question. I'll turn that again over to Dan. Yeah. The easy answer is no, that if folks stay in the trial, they can't go on any anxiolytic or antidepressant. For that full year, for people to stay in the trial, no. No anxiolytics. Now, allowed to is a different question, which is that at all times when people participate in our studies, our sites and our PIs and the clinicians involved make sure to do what's best for the patient. So in cases where someone should go on another therapy that isn't the study drug, the best course of action is for them to withdraw from the study and get the treatment they need. And we always encourage that, far more important than keeping people in the study. But as you see from our retention numbers, the vast majority of patients were able to stay in the study without needing to restart any other anxiolytic or antidepressant. Our next question comes from Pete Stavropoulos from Cantor. Please unmute your line and ask your question. Hi, Rob, Dan, Brandi, and team. Well, congrats on another robust data set. It is not typical to see an effect size seen with DT120 and GAD in this phase III. So when you combine that with the proportion of patients that achieve mild to better category and the response and remission rates you see along with the longer-term part B data. What might that mean for the number of doses for DT120 that may be required over the course of a year for anxiety and for potential pricing implications, but for potential pricing, given the durability you see here, but also in MDD? Yeah. Thanks so much for the question, Pete. I think one of the interesting features there is that, of course, this is very intuitive, but the patients who do the best after a single dose need the least number of doses. We see this very clearly in data, that someone who takes a single dose and has a multi-month, looked out in some for an entire year, in a far improved clinical state without the need for any subsequent treatment. That is a remarkable outcome. That is not the case with everyone, certainly. What we have seen is that the need for subsequent treatment and the number of treatments in anxiety appears to be a little bit less than what we have seen in depression. That may very well be a feature of the disorders, that when we achieve a good response in our anxiety population, there seems to be a sort of trait change that occurs where we see a long-lasting reorientation to the experience of the disorder and a real long-lasting effect. We are going to continue to accrue a ton of data across these indications, and that will inform everything from how we think about informing prescribers and sharing information on the need for retreatment and the likely dynamics of retreatment. It is also going to inform everything we have to decide and move forward with on a commercial and market access and pricing side. A lot to be finalized, a lot to be shared over the coming months and years. Everything is pointing us in a direction where we are seeing, whether it is a single dose or a few doses, this profound efficacy over the course of a long multi-month period. That gives us enormous excitement about every one of those dynamics. Our next question comes from Christopher Chen with Baird. Please unmute your line and ask your question. Hi. Good morning, everyone. Thanks for taking my question, and congrats on the data. Just maybe zooming out big picture, just a BD question. There is obviously been a lot of interest from big pharma with psychedelic space companies, particularly the recent Lilly AtaiBeckley deal. Just big picture, can you discuss whether the nature of any inbound interest has changed since Emerge. Now with Voyage data, do you anticipate additional interest, and how willing are you to listen to those. Thank you. Yeah. Thanks so much for the question, Chris. With data that look like what we have been able to generate this summer, I would be shocked if there is anyone who has come across them who has not had a degree of interest. Wherever that is, we think that these are really eye-opening data and put this drug in the best possible position. We have shown an ability here. We are having an incredible ability to prosecute these clinical programs, regulatory programs, and I think have shown an ability over the last five, six years to really know and do this in a remarkably efficient and thoughtful way. Our focus is on doing the best thing to drive value for our shareholders, to do the best thing to drive value for patients. We have continued to build an absolutely incredible commercial team that is ready to go out and put this in the world in a way that we know it can be done with the most profound impact. That is where our focus remains. That is what our commitment to doing is. Again, we are appreciative of everyone in the world's interest in the things we are doing, whether it be those on the call or those anywhere. We are heads down and focused on the goal here. Our next question comes from Arabella Ng with H.C. Wainwright & Co. Please unmute your line and ask your question. Hi. Thank you so much for taking the question. Congrats on the data. I was just wondering with maybe the potential you mentioned to explore a submission that would allow GAD and MDD in the label. I was wondering if you could comment on the MADRS for those with comorbid MDD in this trial, and then also, I guess, of the 40%, what their baseline MADRS was. Thank you. Yeah. Just very briefly, it's a really an interesting analysis. When we think of the Venn diagram of the overlap between GAD and MDD, we, of course, have seen remarkable effect. The whole circle of GAD in Voyage showed an effect size of 0.81. The whole circle of MDD in Emerge showed an effect size of 0.83. When we look at changes within these studies, there's even more a pronounced effect in patients with anxiety who were in a depressive episode and in patients who had elevated depression scores in our GAD studies, even though they're not in a depressive episode. We think that that's an overlapping part of the circles where we're seeing even larger effects. That just gives us a confidence that no matter where you look, whether it's isolated GAD, isolated MDD, or the overlap, what we're seeing are a really pronounced efficacy, and that, of course, is what you'd hope to see in these populations. Our next question comes from Ami Fadia with Needham. Please unmute your line and ask your question. Thanks for taking my question, and congrats on the really strong data here. I had a question about some of the logistics that the FDA is going to require in the real-world setting and wanted to sort of contrast that with the guidance that they provided to the industry for the clinical trials. My question is, what is the qualification and the number of professionals that the FDA will require in the real-world setting to be monitoring patients? The guidance also talked about the need for a physician to be reachable within 15 minutes in case of a medical emergency. I am curious if you think that that would be required in the real-world setting as well. Thank you. Yeah. Thanks so much for the question, Ami. We are obviously going to have those discussions over the course of a review cycle if we are able to get an NDA on file. We would not want to sort of jump and get ahead of ourselves in speaking for FDA or anything of that nature. What we can say is that when we look at other precedent programs that have had rigid requirements in clinical development, when they transition to real-world setting and REMS, and that the considerations for access and public health are required to be considered and should be considered, those dynamics change dramatically. We also have a number of drugs with, I think, arguably a certainly more acute safety considerations, things like volatile anesthetics that do not specify how anesthesiology should be practiced. There is a delicate balance, of course, with any of these things. We and everyone want these drugs to be delivered safely and in an appropriately controlled setting without over-specifying things that would restrict access and restrict the benefit that the patients could expect. Commenting on any one of these is a sort of overall approach that has to be weighed here. I think that, again, the most encouraging thing across the board is the willingness with FDA and with all of the stakeholders to sit down and have these discussions. We have a really unique opportunity to design a system that can maximize the good that we hope to achieve here. It is really rare to have that opportunity in medicine. The willingness of all those stakeholders to come together to bring different perspectives and to get us, hopefully, to a point that maximizes that is something that we're encouraged by and have certainly been an active participant in shaping. We're incredibly excited about navigating that and navigating all that lies ahead here. Our next question comes from Justin Walsh with JonesTrading. You may now unmute your line and ask your question. Hi. Thanks for taking the question. I was wondering if you can comment on treatment-arm patients that chose not to receive an open-label dose of DT120. Curious both about the potential rationale for not receiving another dose, as well as possible durability of the effect for a single dose of DT120. Yeah. I'll turn that one over to Dan briefly. It's maybe worth commenting, too, on the folks who decided not to continue on in part B of the study, which there weren't that many of, but we thought were kind of an interesting population. Yeah. In order to stay in the study when folks were eligible for a symptom-triggered treatment based on their HAM-A, they had to, within a month, have that treatment. It turns out we didn't really have anybody decide not to. That's not why folks left the study. What Rob mentions here is interesting, which is the people who chose not to go on to part B of the study after part A. One thing that that clearly cost us is the folks who had done extraordinarily well after a single dose and couldn't really imagine a reason that they'd want to stay in a study where they were going to get additional doses because they couldn't imagine a reason they'd need an additional dose. A slight ability to make some longer-term, year-long efficacy claims may have been lost with those folks who moved on. Ultimately, for people who don't hit the retreatment trigger and stay in the study, that gives us exactly what you say, the ability to follow people fully in their initial blinded allocation, with everybody remaining in that fully blinded state for a full year to look at durability of the blinded initial dose. Like we've said repeatedly about the part B, it creates a complicated, somewhat multiaxial data set that's different than the part A data. It also gives us an enormous ability to look at different features of the drug, both in that initial allocation over the long term and what retreatment patterns can look like. That concludes the allotted time for the Q&A session. I will now hand back to Rob Barrow for closing remarks. Yeah. Thank you so much, and thanks again, everyone, for being here today. We've had quite a summer. It's been incredibly exciting to be amidst so much pivotal data and to now have generated extraordinarily compelling data across three studies, across two pivotal studies, and two different indications this summer. We always internally talk about just appreciating this moment and what's going to lie ahead of us. It's, I think, hard to, even for us, to fully appreciate the profound impact this could have on people's lives. I know with GAD in particular, there are many, many people in my life who have been affected by this disorder. To see the excitement over the last several years when we talk about the possibility of something actually changing that and changing what they can hope to expect here. That's why we do this. I think that's why we are dedicated to getting the right people in the organization and having the right strategy so that we can bring this out to the world, hopefully, in a way that really does maximize the good that can be done here. Psychiatry has been waiting for far too long, broadly, for new treatments. But for anxiety, in particular, the clock that we had up, as some of you dialed into the webcast, is something that many of us, I certainly keep on my desktop every single day and look at. Every single day that goes by is another day that the patients don't have something that seems to be potentially transformative for them. We're not going to waste a single moment between here and what lies ahead of us. We, again, incredibly grateful for everyone internally in the company who've been a part of this, everyone who's been connected with making this possible. That includes every single person sitting on the phone today who's been following along, who's been a supporter, who's been part of this journey and will be in the future. Thank you, and we're excited to reconvene here in a few weeks in September to share results from our third pivotal this summer. Hope everyone has a great rest of the week, and again, appreciate your time. This concludes today's conference call. You may now disconnect.