Hello, and Welcome to the Definium Therapeutics phase III Panorama top-line results call. Today's call is being recorded. At this time, all participants are in a listen-only mode. Following the prepared remarks, we'll open the call for questions from covering analysts. I would now like to pass the call over to Rob Barrow, Chief Executive Officer. Please proceed. Hello, everyone, and thank you for joining us this morning. I'm joined today by our Chief Medical Officer, Dr. Dan Karlin, our Chief Financial Officer, Brandi Roberts, and our Chief Commercial Officer, Matt Wiley. We could not be more excited to be here with you this morning to share the top-line results from Panorama, our third pivotal study of DT120 ODT 100 mcgs and our second phase III study in G eneralized 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 discussion of the risks and uncertainties associated with these statements, including the risks described in our most recent annual and quarterly reports. Today's results mark an important milestone for Definium in our DT120 program, as we have now replicated the unprecedented results reported last month from Voyage, our first pivotal study of DT120 in GAD. Having delivered three positive phase III studies across GAD and MDD over the past 12 weeks, our confidence in the transformational potential of DT120 has never been higher. We believe DT120 represents a highly differentiated profile with the potential to redefine standards of care and become a best-in-class therapy across two of the largest and most impactful indications in psychiatry. I'd like to thank our study participants, investigators, partners, and the incredible Definium team for making all of this possible. We are deeply appreciative and humbled by the commitment, trust, and belief in our shared vision. Only together could we have arrived at this remarkable moment. At Definium, we have an ambitious vision and believe 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 anxiety, depression, and other mental health disorders. The burden that GAD places on patients, families, and society is enormous, impairing daily function, productivity, and quality of life, and that burden continues to grow. The prevalence has more than tripled since the early 2000s, and GAD is now estimated to be experienced by 10% of the U.S. adult population. Promisingly, we've entered a new era of far greater awareness and openness around anxiety and its impact on people's lives. Despite this need and awareness, there hasn't been a new drug approved for GAD since 2007. That is not because of a lack of effort. Over that period, roughly a dozen drug candidates spanning numerous mechanisms have advanced into late-stage development. Nearly all have failed, none have been approved, and most have been unable to demonstrate 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 Panorama results we are sharing today continue to change that picture. 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. Panorama marks our third pivotal readout for DT120 this year and our second pivotal readout in GAD. As with our Emerge and Voyage readouts, Panorama met its primary and all key secondary endpoints with a high degree of statistical significance. Consistent positive outcomes across three complementary studies further strengthens our confidence in DT120's potential and the broader opportunity ahead. In Panorama, DT120 ODT 100 mcgs showed a 5.1-point placebo-adjusted improvement over placebo at the week 12 primary endpoint with a P value of less than 0.0001. This efficacy was rapid, with a 5.3-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, both with P values also less than 0.0001. DT120 was well-tolerated with no new safety signals identified, including no suicidality signal. We continued to observe efficient and predictable treatment session dynamics with an average time to clearance on the structured end of session checklist of 6.2 hours and 94% of participants clearing by hour eight. Panorama included a DT120 ODT 50 mcg arm, which served as a functional control but was not powered for or assessed in pre-specified statistical comparisons. The 50 mcg dose produced a 3.6-point improvement over placebo at weeks four and 12, approximately 50% and 29% less than the 100 mcg dose. The results from both Voyage and Panorama are closely aligned with the dose response model generated from our phase II-B study. It is also worth noting that as in phase II, at both the 50 and 100 mcg doses of DT120, over 90% of participants correctly guessed their assignment to drug, supporting the conclusion that the dose response observed is a real treatment effect and is not attributable to functional unblinding. To further emphasize this point, across studies, the 100 mcg dose has consistently exceeded our efficacy target of a placebo-adjusted improvement of at least four points on the HAM-A. The 50 mcg dose has not. At the same time, the adverse event profile was similar across the 50 and 100 mcg doses, and the median time to end of session clearance was six hours for both. In our view, these results decisively settle the question of dose selection and clearly support the advancement of DT120 ODT 100 mcgs. To put these results in perspective, we have now consistently shown that DT120 100 mcgs delivers a large effect that stands out against the current standard of care in GAD at both week 12 and at earlier time points. In summary, in a disorder with high prevalence, high burden, high unmet need, and no innovation in decades, a single dose of DT120 has consistently shown a rapid and durable effect with a magnitude that is considerably larger than the drugs approved today. We could not be more excited about what this could mean for patients and the potential to redefine what they can expect from psychiatric care. With that, I will turn the call over to Dan to walk through the results in greater detail. Thanks, Rob. Today is another important milestone for DT120 and for patients living with GAD. As a psychiatrist, I have seen firsthand the profound impact that chronic anxiety can have on every aspect of a person's life. While existing treatments can help some patients, many continue to struggle with persistent symptoms or wait weeks or months to experience meaningful relief. The positive Voyage results we reported in August marked a major step forward, and today, Panorama provides further confirmation of DT120's potential in GAD. Consistent findings across two phase III trials are especially meaningful because they reinforce the reproducibility of the efficacy signal and the strength of the overall clinical profile. Let me begin with the study design. Panorama is comprised of two parts. Part A, a 12-week randomized double-blind period, and Part B, a 40-week extension period with opportunities for open-label treatment. As in our prior studies, participants were tapered off background antidepressant and anxiolytic medications prior to enrollment. Notably, as with our entire development program, we did not provide any psychotherapeutic intervention as a part of the study. In Part A, 245 participants were randomized in a 2: 1: 2 ratio to receive a single dose of DT120 ODT 100 mcgs, DT120 ODT 50 mcgs as a control, or placebo. The primary endpoint was the change from baseline in HAM-A total score at week 12, assessed by independent central raters, blinded to treatment assignment and visit number. In Part B, participants continued to be followed for an additional 40 weeks and complete regular efficacy assessments. Participants who meet the pre-specified treatment threshold of HAM-A score of 16 or greater become eligible to receive an open-label dose of DT120 for up to four open-label treatments over the course of the study. The treatment threshold of a HAM-A score of 16 corresponds to the cutoff for moderate illness and reflects an increase in symptom burden such that participants are experiencing functional impairments. As in Voyage, we selected this threshold prospectively as a clinically meaningful marker for when additional treatment may be warranted. We randomized 245 participants, 96 to DT120 ODT 100 mcgs, 52 to the DT120 ODT 50 mcg control, and 97 to placebo. All randomized participants were included in the intention to treat population. Approximately 90% of participants completed Part A. Participants entered the study with high disease severity as reflected by baseline HAM-A and CGIS scores of 28 and 4.7 across treatment groups. These values placed participants firmly within the severe range of anxiety. Demographics and baseline disease characteristics were generally balanced across treatment groups. We observed prior psychedelic use consistent with what might be expected in a broad GAD population, with 14% of participants reporting any previous psychedelic use and only 7% reporting prior LSD use. Importantly, these characteristics were balanced across treatment arms, supporting the comparability of the study groups at baseline. Despite a limited number of available treatment options, this population had substantial prior treatment experience and a high disease burden. Half of participants reported receiving two or more prior treatments for GAD, and three-quarters of participants had severe anxiety at baseline. On average, participants had been diagnosed with GAD for approximately nine years and reported experiencing anxiety symptoms from nearly 18 years prior to enrollment. On the HAM-A, which was the study's primary outcome measure, DT120 100 mcgs demonstrated rapid, robust and durable efficacy. At every measured time point, DT120 100 mcgs statistically and clinically exceeded placebo on the HAM-A with a p-value of less than 0.0001. At week four, participants receiving DT120 100 mcgs demonstrated a mean improvement of 12.3 points from baseline, corresponding to a placebo-adjusted difference of seven points. At week 12, the primary endpoint, DT120, achieved a mean improvement of 9.8 points in a placebo-adjusted difference of 5.1 points. Rapid relief is particularly important for patients in distress. By week one, the first efficacy assessment following treatment, participants receiving DT120 100 mcgs showed a mean improvement of 9.8 points from baseline, corresponding to a placebo-adjusted difference of 5.3 points. Taken together, these results demonstrate a treatment profile characterized by rapid onset, robust magnitude of improvement, and durable efficacy through the primary endpoint after a single administration of DT120 100 mcgs. A secondary measure of disease severity is the CGIS, and here we see that CGIS tells essentially the same story as the HAM-A. Key secondary endpoint shown here are change from baseline in CGIS score at week 12 and early improvement measured at day two. Notably, these instruments use different mechanisms to assess the underlying illness and are conducted by different raters. HAM-A is assessed by independent centralized raters, while CGIS is a local site-based clinician-rated measure. The consistency across these independent measures gives us tremendous confidence that the treatment effect represents real, meaningful clinical improvement in study participants. Categorical outcomes provide another way to understand the clinical relevance of the effect. At week 12, 32% of participants receiving DT120 100 mcgs met the response criterion of at least 50% HAM-A improvement, compared with 14% on placebo. 35% achieved mild or better status, compared with 17% on placebo. Remission was achieved by 15% on DT120 100 mcgs and 4% on placebo. Across each threshold, more DT120-treated participants achieved a clinically meaningful outcome after a single administration. The week 12 HAM-A treatment effect was maintained across each subgroup we analyzed. Importantly, the effect was maintained in participants who had received two or more prior GAD medications, a population with substantial unmet need and fewer remaining treatment options. The consistency of the results across these subgroups strengthens our confidence that the benefit observed in Panorama are broadly applicable across the GAD population and are not being driven by any single patient group. Turning to safety. The adverse event profile was consistent with our prior DT120 experience. Adverse events were largely mild to moderate in severity, and most treatment-Emergent adverse events occurred and resolved on dosing day. There were no study drug-related serious adverse events, no suicidal or self-injurious behavior, and no indication of increased drug-related suicide risk. Overall, these findings continue to support a favorable and predictable tolerability profile. treatment-Emergent adverse events were reported in 95% of participants receiving 100 mcgs, 96% receiving 50 mcgs, and 63% receiving placebo. Two treatment-Emergent serious adverse events occurred in the 100 mcg arm, one in the 50 mcg arm, and one in the placebo arm. None of these was study drug-related. No treatment-Emergent adverse events led to discontinuation or death. Adverse events were collected under FDA guidance for psychedelic drug development, which includes expected effects characterized as positive, favorable, or neutral. Among treatment-Emergent adverse events occurring in at least 10% of participants, the most frequently reported events were the expected transient, perceptual, affective, cognitive, and behavioral effects associated with DT120 administration. These events occurred primarily on dosing day, were generally mild to moderate in severity, and resolved during the supervised treatment session. Rob mentioned this earlier, and we believe treatment session dynamics remain one of the most important aspects of DT120's overall profile. 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 shared with you today. We use a structured end of session checklist to assess readiness to leave the treatment setting safely. The average time to clear the checklist was 6.2 hours, with more than half of participants clearing at hour six and 92% clearing by hour eight. Across all 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 cleanly into clinical practice where the end of session checklist can be easily implemented to inform medical decision making by the clinical staff 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 for moderate or worse disease severity as assessed by the centrally rated HAM-A. This phase aims to better understand long-term durability from Part A, subsequent treatment patterns, response to retreatment, and durability over the full year of observation and dosing opportunities. At the time of this analysis, 86 participants originally assigned to DT120 100 mcgs, 42 assigned to the 50 mcg control, and 76 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 anticipated, multiple treatment trajectories Emerge with the 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 results show durability from the initial active dose and additional improvement after open label treatment. Their convergence toward the original active group provides early supportive evidence that subsequent administration can produce additional benefit. Notably, about a quarter of patients in the active arm remain mild or better for roughly six months without needing any additional dose. As with Part A, we can look at response and remission over time in Part B. 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. The consistency of these findings across multiple clinically meaningful endpoints gives us strong confidence in DT120's potential to safely deliver durable efficacy with intermittent symptom-triggered retreatment. With that, I will turn the call back over to Rob. Thanks, Dan. As I said at the outset, our goal at Definium is to enable a new treatment paradigm that can fundamentally reshape clinical practice in psychiatry. We believe the landmark results shared today represent another important step toward that goal. Across four studies with various designs, populations, and indications, DT120 has demonstrated a large, durable effect. While the complementary study designs have yielded differences in symptom presentation and the variance of study outcomes, the magnitude of effect and high degree of statistical significance has remained remarkably consistent. We are nearing completion of our registrational and development program for DT120, which has always been grounded in precise science. This includes four positive Phase II and III studies with complementary designs, a comprehensive clinical pharmacology, non-clinical and CMC program, all of which have benefited from close regulatory engagement under the Breakthrough Therapy Designation program. We have also gone to great lengths to address the key considerations for the development of psychedelics and believe the consistent efficacy and safety data generated to date support a compelling argument for the safety and effectiveness of DT120 ODT 100 mcgs. We are excited to hold our pre-NDA meeting in the fourth quarter, and we anticipate NDA filing for DT120 in the first half of 2027. We believe there is a significant opportunity to bring a differentiated treatment to the patients who continue to need better solutions. 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 view this 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. With such a major need, even modest uptake has the potential to deliver impact for a sizable portion of the population. The large and growing ecosystem of interventional psychiatric clinics provides a springboard for exactly this sort of adoption. With around 8,000 such sites today, if only half of them were to treat two patients per month, this could represent over 100,000 patients in a year. Based on our market research, this is well within the excess capacity that exists today, and we continue to see a high degree of enthusiasm for adoption among these providers. We are making great progress in preparing for commercial execution and the launch of DT120. We've continued to solidify our commercial team with the addition of key leadership over the course of 2026, bringing immense experience and, importantly, a shared philosophy that has driven our success to date. Core to this philosophy is a commitment to delivering the best patient and provider experience possible. We are highly focused and heavily invested in optimizing patient support, provider enablement, and site readiness to help remove barriers and create a seamless treatment experience for all those involved in the process. We continue to make progress on two distinct value drivers, 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 the patients as impactfully as possible. We're working tirelessly to build Definium into a psychiatry powerhouse that can reset expectations for what patients and providers can expect from care. Today's positive Panorama results further strengthen the DT120 story and build on the positive phase III results from Emerge and Voyage, which our team delivered in the past 12 weeks. With approximately $1.1 billion in cash and investments, we are well-positioned to advance toward our planned NDA filing, prepare for commercialization, and continue investing in our broader pipeline. We believe the opportunity ahead is significant, and we look forward to delivering on the many milestones still to come. Before we go to Q and 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. To deliver consistent landmark results in such a rapid succession is truly extraordinary and a testament to the amazing people we have at Definium. With that, we'll open up the call for Q and 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 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'll pause a moment to allow the queue to form. Our first question comes from Paul Matteis from Stifel. Please unmute your line and ask your question. Hey. Good morning. Thanks. Can you guys hear me? We can. Okay, great. Awesome. Thanks so much. Congratulations on the data. I wanted to just ask maybe a two-part regulatory question here. 1, going to this pre-NDA meeting, what are the key questions, and what's your level of confidence that you have enough data to also file for MDD? Then 2nd, can you remind us your agreement with the FDA as it relates to how much redosing data you need. Is it about a certain number of patients getting a certain number of doses, or is this not as quantitatively defined? Thanks so much. Yeah, thanks so much for the questions, Paul. Taking each of those one by one, our overall confidence going into the NDA meeting is extraordinarily high. We've had a very constructive relationship with FDA and continue to have a continuous dialogue there. Of course, with the data we've been able to generate, we think they're unequivocal and really answer the questions that need answering. In terms of alignment on MDD filing, that's exactly the purpose of our pre-NDA meeting is to talk about the filing strategy for GAD and for MDD. Of course, with the recent Breakthrough Therapy designation that we received for MDD, we're very excited about the promise that program holds and the high degree of alignment to efficiently bring that product forward. We'll be eager to get to that pre-NDA meeting and come out of that hopefully with clarity we can offer to everyone about the filing strategy across both the indications. In terms of your second part of your question in redosing, obviously, we all have historically lived under the framework of ICH E1 and the requirement to dose patients at 1,500 independent patients. That's for chronic daily treatments, though. In this case, both the lexicon and the realities of how DT120 and other drugs in the category are being used are not at all like a daily drug. We're talking about a few intermittent administrations over the course of a year. Given the long history and high degree of characterization we have for this program, and just in the phase III studies alone, the over 1,000 treatment sessions that we've now delivered and have data for, we feel quite confident about where we are positioned today and the data we have available to us, which is why we feel comfortable that we'll be in a position to go forward with the filing the first half of next year. Great. Sounds good. Thanks. Thanks, Paul. Thank you. Our next question comes from Andrew Tsai with Jefferies. Please unmute your line and ask your question. Hey, good morning and congratulations on another hugely successful readout. In the, I guess, the eventual label for GAD and MDD, I would be curious how you would envision the front page label claim to read, because we noticed that the FDA's NEJM paper suggests how the FDA is permitting dosing intervals to be established in post-marketing settings. So feels like the front page label claim could be quite broad for you guys. So I would be curious what your thinking is, what you plan to propose to the FDA at the end of the day. Thank you. Yeah. Thanks so much, Andrew. In terms of our development program, our intent has always been to have a front page label that indicates that the DT120 is indicated for the treatment of generalized anxiety disorder and for the treatment of major depressive disorder. Of course, there are other sections of the label where the dose and regimen and administration are described thoroughly. Certainly over time, the historical standard, even for daily antidepressants, has been two acute studies and post-marketing studies then that establish a maintenance regimen. Those maintenance regimen studies are often complex and for many drugs that are already approved, have not succeeded even. So we have not ever seen that be a barrier in a commercial setting to adoption. Based on our dialogue and based on our understanding and the data we have been able to generate today, we are going to be pursuing a broad GAD and MDD label that is not restricted in terms of the exact interval or redosing dynamics because that aligns with what we have been able to demonstrate in the development program. Great. Congratulations. Thanks, Andrew. Thank you. Our next question comes from Gavin Clark-Gartner with Evercore ISI. Please unmute your line and ask your question. Hey, guys. This is Yesha for Gavin. Just a quick one from us. In theory, could the FDA potentially ask you to file the 50 mg in addition to the 100, given what the dose response curve showed? Thank you. Yeah, thanks so much for the question, Yesha. We certainly feel that any questions about 50 mcgs or functional unblinding have been settled by our development program. We have gone to the greatest lengths of anyone in the field to thoroughly interrogate this and to now establish in two studies that in order to derive the kind of efficacy that we are targeting here, the 100-mcg dose is necessary. We would not feel comfortable with pursuing a 50-mcg dose and do not believe that the benefit risk assessment of these two doses would in any way support moving forward with that dose. While we're going to be having those discussions, of course, at pre-NDA and thereafter, we feel quite clear and obviously the data stand up behind that to decisively land on the 100-mcg dose and to really close the chapter on questions about 50 mcgs or functional unblinding or things of this nature. Thank you so much. Thanks. Thank you. Our next question comes from Marc Goodman with Leerink. Please unmute your line and ask your question. Good morning, guys. Just to come back to this new FDA guidance, any general thoughts on anything there? Was there anything surprising there? I am specifically focused on just commercialization and standardization and the monitoring and the dosing and just this end of session checklist and how you think that is going to play into what their commentary is there. Is there going to be a, you have got 94% at 8 hours, so you think the FDA says, "Well, are we at 100% at nine hours, so this is a nine-hour session?" Do you think they are just going to leave it open to interpretation by each clinic? I am just curious how much you think there is standardization there. Thanks. Yeah. It is a really good question, and obviously some place that we have been extremely focused, and I think a reasonable place for all of us to focus. As you correctly identified, we had a 94% ready at hour eight rate, which I might have misspoken previously. But the ultimate, what we are trying to enable here, we are collecting all of these data on end of session checklists. We are trying to standardize in the trials. We examine in a very structured way what actually happens in the treatment room, what treatment session support really consists of. All of that is in service of being able to go to the agency with evidence-based arguments for what the minimum conditions for safety and efficacy are. We have noted throughout this program that by stripping away psychotherapy conduct in the trial, by reducing the role of the treatment session support folks in the room, all of that is in service of establishing these minimum conditions for safety and efficacy. Because at the end of the day, clinical experience and clinical expertise ought to guide the delivery of this treatment in ways that exceed that minimum standard. So our best bet here is to go to the agency, show the curves, show when people are ready. I think there is a pretty strong argument to say that keeping 95% of people in who could be ready to leave because 5% might not be is not absolutely the best move. So that at the end of the day, it is a balance between safety and access and deference to clinical expertise and community standards that will Emerge as we gain experience with this drug in the real world, if approved. One thing that we highlighted here was that we have now had more than 1,000 sessions with DT120 or DT120 mcgs, and of those, 97% are ready to leave by hour eight. I think that is a pretty strong argument for a shorter absolute minimum time, so long as there are standards for what constitutes readiness, and that is what we have established with the checklist now. Thanks. Thank you. Our next question comes from David Amsellem with Piper Sandler. Please unmute your line and ask your question. Hey, thanks. Maybe a question on commercial dynamics. We know GAD is a pretty expansive indication, but I guess in practice, how do you think step-throughs and prior treatments on average are going to shake out before patients can get access to 120? Do you think ultimately this is going to profile as more of the, for lack of a better term, treatment-resistant population who have been through multiple reuptake inhibitors and even ex chronic exposure to benzodiazepine? Just wanted to get a flavor for how you are thinking about that in practice. I realize that that also leans into a discussion on payer dynamics, but would love to get your thoughts. Thanks. Yeah. I will go ahead and turn that over to Dan initially, and certainly can have Matt weigh in, too. Yeah, I have a two-part answer, I think, to this one, which is that, yes, at launch, we fully expect that we will be a step three therapy. That has been the case for every new antidepressant and anxiolytic for quite some time. That has not been a substantial barrier to success, however. By the time a GAD or an MDD patient reaches psychiatry and the sorts of providers who are likely to be our prescribers and provide our treatment session support, they, in many cases, have already had an opportunity to try and been failed by multiple SRIs. I think a benzodiazepine requirement is pretty unlikely given the emerging evidence over the past decade about the effects of benzodiazepines. Yeah, step three therapy, but don't really see that as a substantial obstacle given where patients will be in their treatment journey by the time they reach the opportunity to be prescribed. There's another argument that I'll make very briefly here that certainly we'll hit on more over time, which is that in the prior treatment landscape, where subsequent drugs, where the new branded drugs were effectively the same as the prior drugs, step three seems not unreasonable, right? A drug that has about the same efficacy, about the same mechanism, but costs a lot more. Well, okay, that makes sense to make folks try something that's very similar, but much less expensive. What we see with the data we've been able to present over these past 10 weeks with three positive phase III readouts is a drug that works completely differently. DT120 offers a really different profile for how it can help people's disorder and their experience of their life change. What starts to come out of that is an argument for the step system that previously existed not necessarily making sense, not making people wait and suffer when something that is more likely to help them more conclusively is waiting out there for them. While we'll launch into a step three environment, we think that ultimately there's an argument waiting to be made for some change in the way that the dynamics of treatment courses work. Yeah. This is Matt. Just to dovetail on Dan's comments. We've spent a lot of time talking to payers over the years, and everything that Dan said is consistent with what they've told us. The management of DT120 may be similar to that of esketamine. Prior authorization with a 2x drug failure rate is likely, and that's our plan and operating assumption going to market. Thank you. Our next question comes from Brian Abrahams of RBC Capital Markets. Please unmute your line and ask a question. Hey, guys. Thanks so much for taking my question. Maybe just a follow-up on the payer side. Just wondering if you could characterize your latest payer discussions, just in light of the consistency of efficacy that you're seeing, the robust effects, particularly in these more refractory patients. Any kind of changes or evolution in your view on the potential pricing power here? And congrats again on the data. Yeah. Thanks so much, Brian. I'll comment briefly and turn it over to Matt. We continue to use a benchmark that's out there in the world today, and we're not in a position today, certainly, to announce pricing until much later on a drug like DT120, which typically happens after approval and an interim final rule is issued. But absolutely what you said is correct, which is that we see quite stark efficacy, something that really hasn't been seen before. And in this indication, it hasn't been seen in a very long time. So that certainly gives us a lot of negotiating power and positioning when we think about price. But I'll turn it over to Matt to talk a little bit more in detail. Again, we've spent quite some time with payers, both in research and in advisory roles, and they've been impressed with the data to date. Obviously, with the data over the summer and the data presented today, I think that strengthens our argument with them. And the broad indication set that we're pursuing is also of great interest. So there may be additional value there as we think about the price point, but there's a lot of work to do between now and launch. Thank you. Our next question comes from Ben Burnett with Wells Fargo. Please unmute your line and ask your question. Hey, thanks so much, and I will add my congrats. I wanted to ask just one point of clarification real quick, and that is just on the CGI data, which I believe is slide 17. It just looks like the table is showing a drug effect of -1.1, but the chart or the plot looks more like a -1.0. Just curious if maybe one of those is a modeled estimate. My question is just around the discontinuations. So, great to see no discontinuations due to adverse events. By our estimate, it looks like that maybe five patients or so dropped off in each arm by week 12. Just curious if you had any color on the dropouts. Thank you. Yeah. Thanks so much, Ben. I will turn that over to Dan to talk about the dropouts. Yeah. So no single predominant reason for dropouts. We always see a smattering of different reasons, and sometimes it is just protocol noncompliance or loss to follow-up. One interesting phenomenon, though, that we have seen in these studies that I have not really seen before is people leaving because they are doing extraordinarily well. In any other drug study where you are giving someone daily drug, your folks who sustain the greatest efficacy from getting that daily study drug are unlikely to leave because they only get the drug by staying in the study. Whereas with our study, where we have this 12-week randomized double-blind period with a single treatment session at the beginning, there are certainly people who have a tremendous response right out of the gate there, and as a result, do not really see a reason to continue to participate in a GAD or MDD study. That dynamic's a little bit different. Of course, when someone does extraordinarily well, the modeling that we do to fill in for missing data is going to modulate that to some extent and bring them a bit back toward the medium performance. Beyond that, nothing stands out as being unusual or different from what we would ordinarily see just in the course of a fairly long clinical study. Thank you. Our next question comes from François Brisebois from LifeSci Capital. Please unmute your line and ask your question. All right. Thanks for the question. Congrats on the data. I was just wondering, in terms of the breakdown, have you talked about clinics? I think about 4,000, I believe that was, by taking about half of them. I was just wondering if there's any more work done in terms of how the distribution is amongst the clinics. Would it be two patients a month or something, or are there clinics where there's just so much more volume? If so, what is the reason that you would expect some clinics to have way more volume than other clinics? Yeah. Thanks so much, Frank. There absolutely is a distribution that is, when we look out in the world today, at least in terms of things like esketamine that are delivered, there's a high degree of concentration in a number of centers. In that context, there's certainly a dynamic that could be at play that's driving certain centers to adopt a much higher volume framing and business. It kind of makes sense for a drug that you have to administer up to 56 times a year. You end up doing it a lot and getting in a pattern of retreatment for that drug in particular that requires rapid return by patients and a rapid turnover. In this instance, we obviously don't know yet what the real-world distribution is exactly going to look like, but we feel that there's some really great opportunity here for those sites that maybe don't set themselves up to deliver esketamine or ketamine on a recurrent basis and make that the entirety of their business, but want to offer more treatment options to their patients, perhaps on a regular basis, but not every single day. We certainly expect there will be higher concentrations of prescribers, that there will be some centers that treat a lot more patients than others. But the dynamics here, really what we've been after and what we're seeing is that it opens up a possibility for an even broader set of sites of care and providers that could be involved in the eventual delivery of 120. That's what gets us excited, because that footprint out in the world today is quite large. Our point is that even modest adoption at a modest treatment rate really leads to some incredible opportunities to help many, many patients. For us, as a huge opportunity for value generation. Our focus is going to be going as broad and as impactful as possible as we get out into that setting. Great. Thank you. If I could just, lastly here. In terms of the I know that 50 and 100 weren't powered to be compared to each other, but I was just wondering what you make of the AEs being similar between the 50 and the 100. Also the time, I think it was six hours to leave the clinic. I'm just wondering what we should make of that. Also, in the real world, do we expect the time, once people feel more comfortable, could actually come down for people to be ready to leave the clinic? Thanks. Yeah. I'll turn that one over to Dan. You're noticing exactly the reason that we picked 50 mcgs, which is that to serve as this functional control, not an arm of analytic interest, but there to confound the beliefs of folks who got either placebo or 100. More to confound 100, quite frankly, because of that adverse event profile. What we know is that across the arms that included DT120, both 100 mcgs and 50 mcgs, people detected drug. They knew they got drug, yet we saw this remarkably more effective clinical activity out of 100 mcgs. Again, the AE profile is consistent with the ability to guess one's own allocation, and it means we got the right functional control. Same for the time, really not seeing a markedly different time with the 50 mcg time to readiness. The end of session checklist is something that's evolved somewhat over the course of these studies. We've had a chance now to evaluate its sort of psychometric properties, as it were, across now more than 1,000 sessions. Which has allowed us to refine language and make sure it's clear and easy to use. We think that that will tighten up curves a bit and lead to fewer outliers and really make it an effective and efficient clinical instrument that people will get increasingly comfortable with. Increasingly comfortable with what the end of these sessions look like. Thank you. Be resting. Thank you. Thank you. As a reminder, if you have dialed in and would like to ask a question, please press star nine on your telephone keypad and star six to unmute. That is star nine on your telephone keypad and star six to unmute. Our next question comes from Jay Olson with Oppenheimer. Please unmute your line and ask your question. Oh, hey. Maybe just to follow up on an earlier question about step therapy. From a longer-term perspective, now that you have multiple studies with consistent, overwhelmingly positive results. Meanwhile, the older existing GAD therapies have much smaller effect sizes and less consistent outcomes compared to DT120. Can you just comment on the potential for DT120 to eventually become the new standard of care for GAD and what that could look like? Thank you. Yeah. Thanks so much, Jay. I think I will just take a step back, which is, I think you articulated it quite well. In the context of most psychiatry programs and the history of drug development in this field, it is quite unusual for this many studies and this broad of a set of indications and different study designs to repeatedly deliver such profound activity, such profound efficacy across all of those studies. That is just remarkable. We feel an enormous sense of responsibility and excitement about that reality. As we said, there is obviously a process and there is an evolution over time in terms of where new drugs reside, in terms of market access, patient access, and those dynamics with payers. I will turn it over to Dan to maybe comment. If a patient walked in the door in a practice and you had the option of going down one road that likely led to treatment failures and another that led to the outcomes we are seeing, how he might frame that as a practicing psychiatrist. Feels like a bit of a setup there. The reality is that we want to give patients the best treatment that is most likely to work for them as efficiently as possible. The idea that people can get better from a single or a few doses with a relatively constrained session dynamic and experience that most folks experience as at least positive. That, I think, does have the potential to move into a standard of care. Of course, there is always going to be folks for whom one drug or another, or one experience or another, or one path to recovery is better for them or their choice, and providers will always have preferences as well. But our goal moving forward from here is to continue to build the best body of evidence for the use of DT120 to ensure that for the people who want to pick this path, and are able to, and have a provider who wants to work down this path with them, they can get to it as soon as they can in the course of their illness. Across both of our GAD studies, we saw this really prolonged course of illness that I think has been under-focused on. People suffering for 20 years, being in some form of diagnosis, and in many cases, treatment for 10 years and still being severely ill. That is probably not something that we, as a profession or really as a society, should expect or tolerate. Our argument will always be the same, and will always be evidence-based as best as we are able to say that the point of all of this is to reduce suffering where we are able. Well, super helpful. Thank you. Congrats on these results. Thanks, Jay. Thank you. Our next question comes from Tazeen Ahmad from Bank of America. Please press star six to unmute and ask your question. Hi. Good morning. Thanks for taking my question, and congrats on the additional positive data. As we think about a continuous comparison, let's say, to SPRAVATO and ramping of the launches, can you talk to us about how we should think about the ramp here for, frankly, either indication, if you get both approved? It did take Johnson & Johnson a while to set up all of the infrastructure and educate physicians about the benefits of their drug. Given what additional benefits your treatment would have, is it right to think about this as having a steeper initial uptake curve? If not, what would be needed in order for that curve to start off steeper relative to what SPRAVATO picks up? Thanks. Yeah. Thanks so much, Tazeen. I'll turn it over to Matt to comment a little bit about the ramp, and I'm certainly happy to add anything. Matt, you want to go ahead? Sure. Yeah. Thank you. Thanks for the question. Couple things to consider here. There is no real surrogate for what we are about to do. In thinking about the ramp and the launch curve of the drug, we have a clear understanding of where our administration sites will be. We know where the concentration of patients are and the referring sites as well. We also understand every dynamic that can impact this market, I think much more clearly than other surrogates may have in the past. Even without having a specific playbook for this type of intervention, we do have a clear understanding of every component that is needed to be successful. We have the capabilities, we have the experience, we have the team that this market requires, and we expect to help as many patients as we can as early in the process when we launch, if approved. I will just add one thing on that, which is to say that we absolutely understand the realities that for any new drug such as this, it is going to take some time. But we are, to the greatest extent we can, engaging with sites of care today, engaging with providers. Our MSL team is out in the world to really share this information, understand every single friction point. The goal here is to maximize the footprint when we get this out in the world, and to have every last detail understood to the greatest degree of precision so that we can solve for them, so that we can ease that friction and make it so that we can reach as many patients, as Matt was saying. Again, we recognize it is going to take some time, but we hold ourselves to a different standard than anything that has been out there in the past. Any ramp, regardless of which organization it is coming from, we are going to seek to do better across the board and certainly are eager to get there and show the world what is possible. Thank you. Our next question comes from Sumant Kulkarni from Canaccord Genuity. Please unmute your line and ask your question. Sumant, your line is now open. Please unmute and ask your question. Hi. Thanks for taking my question. Can you hear me? We can. Great. Thanks. Great to see these data, I guess coincidentally, on the day of the public hearing that the FDA is holding on this class of product. How do you see the retreatment paradigm evolving beyond 40 weeks in the real world? From the highly consistent data you've generated and your interactions with payers so far, are there any nuances that could make either indication, GAD or MDD, relatively easier or more difficult to obtain reimbursement for? Thanks. Yeah. Thanks so much. I had a little trouble with audio, but I think that the first question was around research beyond 40 weeks. I will turn that one over to Dan. Yeah. It is something we are incredibly interested in, and quite frankly, it goes beyond the data we will have coming out of these studies. We will know a great deal about what we do in the first year of treatment, and that will allow us to provide substantial guidance in the form of publications on all of the patterns that we are able to observe in that 40-week extension period. We do continue to monitor participants for an additional year, and actually as long as people want to keep giving us data in a remote form, we will keep collecting data from folks who want to. So we will have more than that additional year worth of efficacy from the end of the availability of open label treatment. So we will be able to integrate across that to look out beyond a year. But what we will not have are data for treatment beyond a year. The guidance for treaters will be based on that first year. In essence, as we have said over and over again, it will be based on triggered retreatment that if folks have symptoms, they ought to get drugged. As is usually the case with that kind of triggered label, it will be optimized treatment to maintain optimal patient response sort of language. So we expect that will continue. What we do know from some things outside of our research, from some other research, and from compassionate use programs outside of the U.S., is that over time, people tend to require less drug. So that whatever amount of drug helps people get into mild or better in the first year, it will take less in the second. What we have seen out in the world is that in many cases, people do not continue to require drug, and are better functionally. We have not really had an opportunity to do a thing like that in psychiatry before. So we will set up structures and systems so that we can look at real-world use if approved, and be sure that we are capturing all of the data that we need to inform long-term treatment in addition to that early phase of treatment. But that is our goal, is to learn as much as we can about that as we move forward. Thanks, Dan. I will just say on the payer side, we feel really comfortable with where we are for both these indications. Obviously, it is going to be subject to additional engagement, discussions, and finalization. But regardless of what is on a label when, both of these are highly impactful, high burden disorders that cost payers quite a bit of money. We look at examples out in the world of where predictable, rapid, durable efficacy can be had. That makes a difference not only for patients' lives, but makes a difference for payer budgets. We are obviously very much aware of that as we think about everything from here. Thanks. Thank you. Our next question comes from Pete Stavropoulos with Cantor. Please unmute your line and ask your question. Good morning, Rob, Dan, and team, congrats on another robust data set. How should we be thinking about DT120 monotherapy versus adjunctive therapy for both GAD and MDD in the real-world setting? Patients staying on their background anxiolytic or antidepressant therapy. Is it something you may try to address via small clinical study or just it will get sorted out in clinical practice? What are your expectations and what is the feedback from consultants and KOLs on this? Yeah. Thanks so much, Pete. Turn that one over to Dan as well. Yeah. It's a great question. Something again that we've thought about quite a bit. As everyone listening will know, for the conduct of our phase III studies, we took background medications off prior to treatment. That's largely for the interpretability of the research to try to control another condition that we could control, so to reduce variability. We don't think that'll be necessary in the real world. Psychiatry has gotten very comfortable with, perhaps too comfortable with polypharmacy. While the vast majority of drugs that are ultimately labeled as monotherapies were tested as monotherapies, in almost all cases, those are used as a component of polypharmacy. We don't think that the provider base, based on the conversations we're out there having with them, are going to be reluctant to make individualized patient decisions, to try to do whatever is best for a patient. If a patient is sustaining some benefit from background med, treat them DT120 first, and then take off the background med once they're feeling better, if they're feeling better. We are doing exactly as you say, some additional research to ensure that we've got the ability to go out and detail on that and publish on it to establish that the transient effects of DT120 aren't mediated by background anxiolytic or antidepressant medications. Doing the work, but absolutely expect that that will be an individualized clinical decision that's made at the point of care. All right. Thank you very much, and congrats on the data again. Thanks, Pete. Thank you. Our next question comes from Chris Chen with Baird. Please unmute your line and ask your question. Hi, everyone. Good morning, and congrats on the data again. Just a quick one on dose responses. I did notice at week one, the 50 mcg arm did show a slightly greater improvement on the HAM-A than the 100 mcg arm. The curves invert afterwards. I think this phenomenon did happen in the phase II-B between the 200 mcg and 100 mcg dose, but not between the 50 and 100 mcgs. Just curious what you think is explaining that. Thank you. Yeah. Thanks so much, Chris. I think really what you're describing is kind of exact confirmation of what we're seeing here, which is that 50, as you would expect with any drug, a lower dose, a dose that's about half, has some initial activity. Especially here, we see the drug has some action, right? In some patients it's quite large, but when we do studies and we think about the conclusions and the means, we use means because we're trying to establish evidence for the broad population out in the world, right? The transition here is not purely academic or scientific interests. It's how do we find a drug and establish and confirm the efficacy and the tolerability and safety so that it can be used by clinicians and by patients out in the world. What we see is reliably that 50 does not have the activity that drives durable or large enough change for what we are desiring here. We see that initial reaction, and in this context here, you could see some of those patients who have an initial reaction, but beyond a week that pretty rapidly fades. That's not the profile of the drug we're developing here. The reason why we established 12-week primary endpoint in the study is because we're so focused on the durability of action here, and the ability to drive that large change simply requires 100 mcgs. The other trade-off we see is that there's no sort of reduction in tolerability profile, at least in the studies we have to date, right? If there's no added benefit to going to 50, as we've seen, there certainly is no worsening of safety or difference in tolerability profile between 50 and 100. There just isn't a rationale for why you wouldn't use a more efficacious dose, that we've now seen repeatedly beyond mcgs. Certainly seeing that initial response is actually quite interesting to us as well. But looking at the curves and looking at data overall in the context of the full development program, again, we feel remarkably clear on the data and the fact that 100 mcg dose was and is the right dose to bring forward. Makes sense. Thanks so much. Congrats again. Cheers. Thank you. Our next question comes from Ami Fadia with Needham. Please unmute your line and ask your question. Hi. Good morning. Congrats on the really strong data. My question was about the patients that did not need retreatment for up to six months. Did you look at any correlation between either baseline characteristics or whether or not the patient achieved remission and see if there was any sort of way to predict which would be the patients that can go longest without requiring retreatment? If you can comment on any experience from any of the other phase III trials as well, that would be helpful. Thank you. Thanks so much, Ami. We're of course, going to continue to interrogate that and try to really find an answer. If we could identify exactly the people who are going to respond, that would be a remarkable finding, not only for our program, but for the entire field of psychiatry. We've yet to see anything that is a sort of decidedly clear marker on who going into the first treatment is going to be a responder. I think the really interesting thing here, though, and it's something that is really important and I think often overlooked, is that what we do see is that early response is quite predictive of more durable response. That shouldn't be a terrible surprise in the context of what we're seeing, but it isn't always the case for drugs, and particularly the drugs that are out there today, right? Patients start on drugs and often go weeks or months without knowing whether it's actually going to sustain efficacy. Even when there is an initial response, that can often wane over time. Here what we're seeing is that within a few days, as early as we measure it, the earliest measured response is quite useful in determining whether a patient is going to respond and that response is going to be durable. With those kind of dynamics, of course, if for a provider and for a patient and for payers, if you can find out very quickly whether it's the right drug for a patient or not, that would be a great outcome and have some really nice characteristics for all those stakeholders. What we're seeing is really exciting, but we're going to keep digging and keep trying to identify if there's anything, of course, that could prospectively be able to define the likeliness of treatment response. Be really cool if there is. Thank you. Our last question comes from Rudy Li with Wolfe. Please unmute your line and ask your question. Hey, thanks for taking my question, and congrats on the strong data. Can you maybe provide additional color on the economics of DT120 treatment sessions for the centers? Based on current CPT code, what do you think will be the key differences versus Berado's buy and build model, and any key learnings for you from today's public hearing for that day? Thanks. Yeah. Thanks so much, Rudy. Yeah. Thanks so much. Just on a high level, I think we're obviously a detailed understanding of site economics and of the economics that we're anticipating for 120. Little premature to say decisively what they are going to be. I think the important thing for everyone to understand is that while there are opportunities for unique codes and while drug-specific J-codes are something that we're very focused on, by and large, the sort of infrastructure and the administrative aspects of coding and billing exists, and we don't need to recreate a billing system in order to have a direct path to adoption. So we feel like that's something that probably out in the world is not fully understood, and it's a very specific conversation, and requires a level of detail, both in this context and for sites of care. But that is exactly what our commercial team is focused on and what we are going to be solving for over the years to come as we get ready and get selling in the market. In terms of hearing, we are excited to have the public conversation continue, and continue to hear from a number of stakeholders. We have always said we have an extraordinary opportunity to really look out into the future and, certainly with the evidence we have generated to date, sit down and have these conversations about how to design a framework for these products to be safely adopted in the world, and also get them out to patients at a remarkable scale. That has been the goal all along. The more voices we hear in that process, the better, and the better, hopefully, we can collectively design a system that balances access and the need. Thank you. That concludes the allotted time for the Q and A session. I will now hand back to Rob Barrow for closing remarks. Yeah, with that, thanks again, everyone, for joining today. It has been an absolutely incredible summer to have three pivotal studies read out in such quick succession is quite unique and something that we are really proud of, and certainly could not be more grateful to our team and to everyone who has been a part of this in the process. We are going from one sprint to another. We are so excited to take the next steps here, to move forward, have a pre-NDA meeting, and to get ourselves ready for an NDA application, an NDA filing, and to get ready for a launch of a product if we are able to get it approved. We have such a remarkable opportunity ahead of us, and we are fully committed to doing everything possible to recognize that. Thank you again to everyone who has been here today, everyone who has been involved in the process from the beginning, and we look forward to sharing in that continued path forward and continued success in the years to come. Thank you. This concludes today's conference call. You may now disconnect.