DFTX

Good afternoon. I am Gita Jain, Head of Investor Relations, and thank you for joining us today for Definium Therapeutics' first quarter 2026 financial results and recent highlights conference call. Currently, all participants are in listen-only mode. This webcast is live on the investors section of Definium's website at definiumtx.com, and a replay will be available after the webcast. Leading the call today will be Rob Barrow, our Chief Executive Officer, who is joined by Dr. Dan Karlin, our Chief Medical Officer, Brandi Roberts, our Chief Financial Officer, and Matt Wiley, our Chief Commercial Officer. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, our anticipated cash runway, and our future expectations, plans, partnerships, and prospects.

These statements are subject to various risks, such as changes in market conditions and difficulties associated with research and development and regulatory approval processes. These and other risk factors are described in the filings made with the SEC and the applicable Canadian securities regulators, including our annual report on Form 10-K and our Form 10-Q filed today. Forward-looking statements are based on the assumptions, opinions, and estimates of management at the date the statements are made, including the non-occurrence of the risks and uncertainties that are described in the filings made with the SEC and the applicable Canadian securities regulators or other significant events occurring outside of Definium's normal course of business. You are cautioned not to place undue reliance on these forward-looking statements which are made as of today, May 7, 2026.

Definium disclaims any obligation to update such statements, even if management's views change, except as required by law. With that, let me turn the call over to Rob.

Thank you, Gita, and thank you all for joining us today. The first quarter of 2026 marked a strong start to what we believe will be a pivotal year for Definium. We remain highly focused on disciplined execution as we have advanced our late-stage clinical programs, prepared for multiple near-term data readouts, and continued to build an incredible team to lead our potential commercialization efforts. As we discussed at our Investor and Analyst Day a few weeks ago, Definium is entering a period of meaningful clinical inflection. Our lead program, DT120 ODT, is advancing with four ongoing phase III studies across major depressive disorder, or MDD, and generalized anxiety disorder, or GAD, with top line data from Emerge expected later this quarter, followed by Voyage and Panorama in the third quarter.

Our phase III programs are designed to evaluate outcomes that we believe would represent a meaningful advance for patients, physicians, and the field of psychiatry. These include not only the magnitude of symptom improvement, but also safety, tolerability, and durability of response following a single administration, dimensions we believe will be critical in differentiating DT120 ODT in today's treatment landscape. We're also encouraged by the increasing recognition of the significant unmet need in these indications. With three phase III readouts anticipated across two of the largest indications in psychiatry, Definium is approaching an important moment for the company and for the patients we aim to help. With breakthrough therapy designation for DT120 and GAD, we have established a constructive working relationship with FDA and will move as efficiently as possible towards an NDA submission subject to positive pivotal data.

Beyond our ongoing phase III programs, we plan to expand development of DT120 ODT into additional indications, including post-traumatic stress disorder, or PTSD, with the planned initiation of our Haven study in 2027. We believe this represents an important opportunity to further leverage the potential of DT120 across areas of high unmet need. Overall, we continue to believe in DT120 ODT as a potential best-in-class product candidate, one that could help redefine what's possible for the millions of people living with depression, anxiety, and PTSD who remain underserved by existing treatments. I'll now turn it over to Dan to go into more detail on our clinical programs. Dan?

Thanks, Rob. I'll provide an update on the status of our clinical programs with a focus on where each of our late-stage studies stands today and how those studies were designed to assess what we believe would constitute a clinically meaningful outcome, starting with DT120 ODT. Our lead program continues to advance across phase III studies in major depressive disorder, generalized anxiety disorder, and now post-traumatic stress disorder. In Emerge, our first phase III study in MDD, enrollment is complete with 149 participants. We are now in the final stages of trial execution and data preparation, and we remain on track to report top-line results later this quarter. In GAD, we are rapidly approaching top-line data readouts for our two pivotal studies, Voyage and Panorama. Enrollment in Voyage is complete with 214 participants.

We have exceeded our updated enrollment target of 200 participants in Panorama and expect to complete enrollment this month. We continue to expect top-line data from Voyage early in the third quarter and Panorama late in the third quarter. Across our pivotal program, our focus has been on rigorous execution, data quality, and consistency across studies and sites. These are large, well-controlled trials designed to evaluate the magnitude of improvement alongside safety and durability of response following a single administration of DT120 ODT. Given our confidence in the clinical profile of DT120 and the strong evidence we have generated to date, our approach is uniquely designed to establish the durability of a single treatment for at least 12 weeks. Our phase III studies in MDD and GAD were initially powered to detect a placebo-adjusted difference of five points.

As part of the protocol-specified design, we conducted sample size re-estimations in Voyage and Panorama. These analyses were performed without unblinding treatment assignments and were intended to assess key nuisance parameters, standard deviation, and dropout rates to support the maintenance of the intended statistical power. Based on these blinded analyses, which were conducted when half of participants reached the 12-week time point, Voyage and Panorama are now powered at 99% or greater to detect a five-point placebo-adjusted difference, assuming these nuisance parameters remain consistent in the final study analysis. For Emerge, the study was powered at 80% to detect a five-point placebo-adjusted change, with statistical significance expected at a little over a three-point difference based on certain nuisance parameter assumptions. We selected this level of power intentionally as we believe a three-point or more difference represents an appropriate threshold for clinical meaningfulness in MDD.

It's also worth noting that Emerge has a six-week primary endpoint compared to 12 weeks for Voyage and Panorama, mitigating the risk of an elevated dropout rate in the primary analysis. Additionally, while the studies were powered to detect a five-point difference, we believe that a placebo-adjusted improvement of four points or greater six to 12 weeks after treatment would compare favorably to currently available treatments for GAD and MDD and to other product candidates in the psychedelic category. Durability remains a particularly important dimension for psychedelics. In our phase II program in GAD, DT120 demonstrated durability through 12 weeks following a single administration of 100 mcg. Our phase III trials are designed to further evaluate consistency and duration of response over time.

Through part B of these studies, patients are followed for up to one year, which we believe will provide important information to inform potential labeling, including how frequently treatment may be needed. Beyond DT120, we are excited to also be advancing our phase II study of DT402 in autism spectrum disorder or ASD. DT402, the R-enantiomer of MDMA, has shown promising pro-social effects with a potentially favorable tolerability profile. We are developing DT402 to target the core characteristics of ASD, specifically addressing social communication that is central to the experience of the disorder. We see this program as a significant opportunity given the high unmet need, the increasing prevalence of ASD, and no FDA-approved therapies that specifically address these core characteristics.

As we look ahead, the next five months represent a significant culmination of thoughtful trial design, disciplined execution, and years of work focused on addressing some of the most pressing unmet needs in psychiatry. With multiple phase III readouts approaching, we believe we are well positioned to deliver decisive data on DT120. With that, I'll turn the call over to Matt to discuss our commercial strategy and the broader treatment landscape. Matt.

Thanks, Dan. I'll spend a few minutes discussing the commercial opportunity for DT120, building on what we shared at our Investor and Analyst Day in April. As we discussed, GAD and MDD represent very large and persistently underserved markets. Many existing medicines are constrained by delayed onset, partial or inconsistent efficacy, and tolerability issues that drive high discontinuation rates. Across this landscape, roughly 4.2 million U.S. adults have cycled through two or more treatments without sustained benefit. A population that sits at the center of our initial launch focus. We believe that these patients and the physicians treating them are actively looking for a next generation option that works differently and can deliver durable improvement without the need for chronic daily dosing.

To put the scale of this opportunity in perspective and using SPRAVATO's average annual price as a surrogate, capturing just 1% of the total addressable market in these indications represents potential for a roughly $2 billion annual revenue opportunity. Our targeting model is built directly around this substantial unmet need. We have identified high volume healthcare practitioners, primarily psychiatrists and psychiatric nurse practitioners, who manage concentrated populations of these specific patients. These high volume prescribers are located within psychiatric practices, behavioral health networks, and select integrated health systems where these patients most often receive care. We have mapped these priority targets in detail and plan to focus our launch efforts on engaging these clinicians, particularly those who have experience with or have expressed interest in novel in-office interventions and supported by care teams capable of monitoring patients during the dosing day.

We believe this approach will enable us to reach a meaningful number of appropriate patients from the outset while establishing a strong foundation for scalable adoption. One of the points we highlighted at our Investor and Analyst Day is the growing awareness of DT120 among clinicians. Through ongoing engagement, we've seen increasing familiarity with its clinical profile and strong interest as a potential new treatment option that could help patients move beyond therapies that are no longer providing adequate or lasting relief. We also shared data showing that patients discontinue current treatments at a high rate, often due to lack of efficacy or tolerability. These challenges are especially pronounced among patients who have been failed by two or more prior therapies, reinforcing the substantial opportunity for differentiated innovations like DT120. Our commercial strategy is shaped by these realities.

We are focused on how this therapy can be introduced in a way that is scalable, accessible, and practical within real-world care settings without the necessity of chronic interventions. A key element of our planning includes a centralized hub support model and additional field support to enable a frictionless process of adoption and delivery. In parallel, we continue to engage with physicians, payers, and other stakeholders to better understand decision drivers around adoption, patient identification, and reimbursement frameworks. By pairing a well-articulated unmet need in a receptive market with our disciplined patient-centric commercial strategy, Definium is very well positioned as we near pivotal data readouts and advance DT120 toward potential commercial launch. With that, I'll turn it over to Brandi to discuss our financial results.

Thanks, Matt. Before walking through our financial results, I want to briefly set the context for how we're thinking about capital deployment as we move through an important phase for Definium. As we entered 2026, we were pleased to have the financial flexibility to accelerate several key initiatives in parallel, including ongoing phase III execution, NDA preparation activities, market access priorities, and continued engagement with key opinion leaders and leading practitioners. These investments are intended to support our path forward and if DT120 is approved, position the company to be well prepared for a robust, thoughtful commercial launch. We've also been encouraged by the continued evolution of our investor base in 2026 with strong engagement from existing shareholders and growing interest from new investors as we made progress across our programs.

We believe this reflects increasing recognition of the opportunity ahead as well as confidence in our disciplined approach to execution and capital allocation. I'll now turn to our financial results for Q1 2026, which are detailed in the earnings release we issued this afternoon. Research and development expenses were $41.5 million compared to $23.4 million for Q1 2025. The net increase of $18.1 million was primarily driven by increases of $15.2 million in DT120 program expenses, $3.2 million in internal personnel costs as a result of expanding our R&D capabilities, and $0.3 million in DT402 program expenses, partially offset by a $0.6 million reduction in preclinical and other program expenses.

For Q1 2026, general and administrative expenses were $17.7 million compared to $8.8 million for Q1 2025. The net increase of $8.9 million was primarily due to increases of $3.9 million in stock-based compensation expenses, $1.4 million in personnel-related expenses, $1.4 million in commercial preparedness-related expenses, $1.4 million in corporate and government affairs expenses, and $1.2 million in legal and patent expenses, partially offset by a $0.4 million reduction in other miscellaneous administrative expenses. The year-over-year increase in G&A expenses reflects deliberate investment to support a more mature organization as we prepare for our anticipated phase III top-line data readouts and potential commercialization.

Overall, our R&D and G&A expenses for the first quarter were in line with our internal expectations as we continue to make meaningful progress across the DT120 and DT402 programs. Net loss for Q1 2026 was $77.1 million compared to $23.3 million for Q1 2025. As a reminder, our net loss can be significantly impacted by changes in the fair value of our 2022 USD financing warrants, which are marked to market each quarter. For Q1 2026, the impact on net loss from the change in fair value was $20 million, reflecting an increase in our share price from $13.39 at December 31st, 2025 to $18.90 at March 31st, 2026.

Turning to the balance sheet, we ended Q1 2026 with $373.4 million in cash equivalents, and investments. We believe our capital position provides sufficient runway to fund planned operations through multiple anticipated clinical readouts and into 2028. 2026 is shaping up to be a data-rich and strategically important year for Definium. Our financial position allows us to remain focused on disciplined execution while maintaining the flexibility needed to support our priorities and continue building long-term value for shareholders. With that, I'll turn the call back to Rob.

Thanks, Brandi. After years of thoughtful trial design and focused execution, we are entering a period of numerous pivotal milestones that we expect will define the next chapter for Definium in our broader field. As we mark Mental Health Awareness Month, the urgency of advancing new treatment options and the responsibility we carry for patients feels especially pronounced. Before we close, I want to say thank you to our incredible team, the investigators and their teams, and to the hundreds of patients who have made this work possible. With that, we're happy to take your questions.

Thank you. At this time, we'll conduct a question and answer session. As a reminder to ask a question, you'll need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster.

First question, [audio distortion] your line is now open.

I'm sorry, you cut out for a second. This is for Paul.

Oh, yes, your line is now open, Paul.

Hi, this is Emily on for Paul Matteis at Stifel. We just had a quick question on assuming, you know, you have success in MDD and anxiety this year. Could you maybe speak more to your thoughts around how much long-term safety and retreatment data you would need for approval? In these long-term data, would patients need to retreat a certain amount of times to count as a long-term exposure for safety? Thank you.

Great. Yeah. Thanks so much, Emily. I'll speak briefly to this and then turn it over to Dan to maybe elaborate. We've had a great dialogue with FDA over the past several years and obviously building towards an eventual plan for an NDA submission subject to positive data and all that has to happen to get ready for an NDA, which we're very well positioned for. In terms of safety data and what's required, we feel really comfortable with the completion of part A and the data that we'll have available at the time of filing and at various milestones between here and there. We have sufficient safety exposure, both single dose and over longer periods of time.

Of course, the interesting dynamic with drugs that you don't have to take continuously or daily or in a very short fixed interval, like the treatments we have today, is that treatments patterns that diverge across different patient populations or different patients can mean that six months of treatment can look like one dose or multiple doses. Something we're really interested in characterizing, of course, in our phase III program. Regardless, we feel very well positioned with the studies we're conducting that we'll be in a great position to move forward, so we deposit phase III data. Dan, you wanna add any color to that?

Yeah, I mean, I guess I could elaborate just a tiny bit on part of the value of the part Bs of these studies where we're able to deliver triggered treatment based on people having moderate symptoms of GAD or MDD or worse, moderate or severe. The value of that is multifold, really, which is that one, it helps keep people in the part A of the study. As you saw from our announced sample size re-estimation outputs, our dropout rates are really quite remarkably low, in part because people know that they have this opportunity if they're still safe to get open label treatment in part B.

The ability to follow folks long term for up to a year after their initial blinded dose is another advantage of these studies, right? For folks who get to mild illness or better, we just get to keep watching them in that initial controlled blinded state unless they get sick again and until they get sick again, if they in fact do. That's another advantage. As Rob said, in those part Bs, we get to give up to four additional open label treatments contingent on people developing moderate illness or worse.

That will give us the ability to start to really carefully characterize across these studies the patterns of treatment that emerge when treating people with moderate or worse symptoms, which maps pretty well onto what we think would likely happen in the real world if approved. With all of those data in hand, we're confident that we will have everything we need to both inform FDA and then of course, to inform the clinical and patient community if we do get approved.

Great. That's super helpful and congrats on the quarter.

Thank you. One moment for our next question. Our next question comes from the line of David Amsellem of Piper Sandler. Your line is now open.

Thanks. Just a couple from me. One, in terms of the patient experience. In terms of patient monitoring, how confident are you that in practice only one dosing session monitor will be needed to monitor the patient? That's number one, sort of a, I guess, REMS-related question on that front. Secondly, I have a question on the PTSD, Haven study. Just a little bit of color, if you can, on the thought process behind running Haven as just a straight up active versus placebo, as opposed to including a low 50 mcg dose arm. Just love to get your thoughts on your thought process on that. Thanks.

Thanks so much, David. Yeah. Dan, I'll turn it back over to you.

Yeah. Great question. The situation in the clinical trials, of course, is that per FDA direction, we have an in-person lead monitor and then a secondary monitor who can watch remotely via video. That's been the condition for conduct of clinical trials based on FDA direction. Throughout the trials, we have made every effort to collect regulatory grade data on what those monitors are doing, to provide for assistance and comfort for the patients, up to and including what the role of that second monitor actually ends up being. All of this is in service of making the case that a single monitor is absolutely something that should be enabled in the real world. That's our position.

You know, in the longer term here, if you look at other therapies that have acute consciousness altering effects, things like monitoring ratios haven't been explicitly specified. At the end of the day, it's been left to clinical discretion and clinical judgment to ensure that the patients are safely monitored. Of course, there's some contents in existing REMS, and we'll expect to have content in our REMS that relate to monitoring. You know, with the evidence that we're accumulating along the way, adheres to the evidence that we've been able to establish for what constitutes safety and efficacy. I can comment on PTSD as well if you'd like, Rob.

Yeah. Please, that sounds great.

Yeah, sure. Across the phase III program, we have combined studies, right? We've got studies with two arms, and then in two cases, we've added this lower enrolling, 50 mcg confounding arm, right? That's not an analytical arm. It's an arm where we're interested in the performance of the 50 mcg drug. Rather, those arms have existed to confound the understanding of people in the other arms as to what they got. In each case, for GAD and MDD, our first study in the condition, we used a two-arm design with an inert placebo, which we continue to believe is the appropriate control condition for testing psychiatric medications including DT120 and, you know, any other psychedelic for that matter. That's what we did in PTSD.

We think head-to-head is the best way to establish evidence of efficacy. As we've gathered the accumulated evidence and as we're able to read out the evidence from these other three studies that we're conducting and ultimately from Ascend, which we've guided us, you know, starting imminently. All of that will accumulate to help us understand what, if any, effect that 50 mcg dose arm has on the understanding of people in the other arms as to what dose of drug they got and whether they got a treatment dose or not. Also whether that has any effect on the measured outcomes.

As we gain more knowledge and information about the performance of these different studies with the different control and confounding conditions, that will allow us to think about future studies and the design of those studies. For primary evidence of efficacy, we continue to believe head-to-head is the right control condition.

Okay. That's helpful. Thank you.

Thank you. One moment for our next question. Our next question comes on line of Andrew Tsai of Jefferies. Your line is now open.

Hi. It's Brian [audio distortion] on for Andrew Tsai. Just two questions. First, on patient journey, you've mentioned the phase III will be a five to eight-hour patient journey as opposed to up to 12 hours in phase II. Can you just talk a bit about what gets you closest to the five-hour journey as opposed to eight? What do you need to establish with the FDA incentives to make it happen? Secondly, on placebo response. Your placebo response in phase II, the GAD study was actually very high when compared to other GAD studies. How are you thinking placebo might trend in the phase IIIs? Then same goes for the phase III MDD study as well. Thank you.

Thanks so much, Brian. I think in terms of the first question, the criteria, some of the changes, we highlighted this a few weeks ago at our event. Both formulation, where we use an orally dissolving tablet in our phase III program, where we see faster absorption we think could translate into, you know, a better profile in terms of resolution of the symptoms. Also the way we've approached this, it's been intentional from day one. We started with little information about the actual safety requirements and monitoring dynamics in these studies when we were going into our phase II program. We included a higher dose, 200 mcg dose in phase II.

Therefore conservatively, and I think appropriately conservatively, extended the monitoring period in phase II out to 12 hours and had a extremely lengthy set of criteria that were being measured to assess when patients could end the monitoring session. Based on those learnings, based on those data from the phase II study, we made revisions, both, of course, to the formulation, but also to that procedure, that checklist that we're using. In phase III, we feel quite confident that we'll be moving in a shorter direction. That's what we certainly are seeing so far.

I think that combined with the reality that the change from a 12-hour monitoring period to an eight-hour monitoring period being required for all the participants in the study was driven by discussions with FDA and based on those data. We feel quite confident that we're heading in the right direction there. That regardless, within that window, we see a really attractive clinical profile, one that means that patients aren't shuffled through and rushed out the door, and one that means that providers have a low turnover, high efficiency delivery to those patients. In terms of the second question, placebo response. You rightly noted we had a remarkably high placebo response from the phase II study.

If we just focus on the GAD symptoms or GAD HAM-A scores for a moment, what we saw there is, and this would be consistent across any modality in almost any scale. The fact that an 80% likelihood for patients to be receiving some dose of drug tends to drive up placebo response. We also saw that around a third of patients who received placebo guessed they were on drug. The presence of several lower doses likely really enhanced that placebo response.

There are also dynamics with the dropout of patients, where we didn't have anything to offer patients beyond the initial dose in phase II, that we now in phase III have part B, and patients are guaranteed access to open-label drug if they continue on through the 12 weeks of the study. All of those dynamics, we think played a role in the phase II. As we look to the phase III program, having a lower allocation ratio, and having a reason for patients to stay in the study, should both reduce at least to and perhaps even below historical averages for the placebo response. That would be true we'd expect in both GAD and in MDD. I think we see this from other programs as well.

We look at other studies in our category. We look at the pivotal studies for SPRAVATO. We're seeing lower placebo responses than we have historically seen for antidepressant in daily drug studies. It wouldn't be surprising if we saw a lower than average placebo response across the phase III programs here. Given that we've exceeded such a high placebo by such a wide margin in phase II, we feel, you know, quite confident no matter what that we'll be in a great position heading into the phase III data.

Thank you. One moment for our next question. Our next question comes from the line of Marc Goodman of Leerink Partners. Your line is now open.

Hi, good afternoon. This is Basma on for Marc. Thank you for taking our questions. Our first question is about the PTSD program. Can you remind us again of your convictions regarding the dose using the PTSD? Why do you think it's gonna be efficacious? Also, can you remind us of the study powering assumptions? The second question is, do you think for the submission in MDD or the GAD, whatever comes next, that you can leverage the safety data from the GAD, or you're gonna have to collect another set of exposure data in the relevant patient population? That's it for us. Thank you.

I'll take the second one first and then turn it over to Dan. You know, we certainly expect to have exposure from pivotal studies and efficacy studies in any population that we're conducting research in, of course. ICH guidelines aren't specific for patient exposures, aren't disease or disorder specific. Certainly would expect a huge population requirement like you see from ICH E1 or anything. Dan, I'll turn it over to you to the other one.

Yeah. Great question about PTSD and, you know, having done our dose range finding study in phase II and getting great confidence in our phase III dose and dose in this formulation through some transitional PK work that we've done there, gave us the confidence to go forward in GAD and MDD. As you note, the confidence also to go forward in PTSD with that dose.

We have every reason to think that from a symptomatic perspective, from a disease definition overlap perspective, from a scale overlap perspective, that all of those come into alignment and that there's no real reason to think that the variations that make up these differently defined diseases, but that fundamentally have such tremendous overlap would call for any additional dose adjustment moving forward. We go into PTSD with the same confidence we went into to MDD with the dose that we selected initially for patients with primary GAD. From a powering perspective, we continue to look at this like five-point change on the scale as being a really good sweet spot for us to aim for.

You know, we're continuing to think about that across the scales, whether the scale is the HAM-A for GAD, the MADRS for MDD or the CAPS for PTSD.

Thank you very much. That's very helpful.

Thank you. One moment for our next question. Our next question comes from the line of François Brisebois of LifeSci Capital. Your line is now open.

Hi. Thanks for taking the question. You talk about the overlap here, and I just want maybe a better understanding of it seems like MDD is more episodic, but with GAD and just in terms of, you know, probability of success or whatnot of the trials, is there, you know, is there more confidence in one versus the other? To that point, is there anything about the disease itself with GAD that could trigger a higher placebo response, or is this more from the kind of trial design, we think, like you mentioned?

Yeah. Thanks so much, Frank. I'll turn that one back over to Dan as well.

Yeah. It's a great question, Frank. We've said this in a few different ways, obviously we've introduced some new slides from the deck now to look at the GAD MDD overlap. As you noted, it really is in the vast majority of patients, something of a temporal distinction that these are folks who, you know, if they have MDD, it's because they have had or are currently in a major depressive episode. Major depressive episodes by their definition end, they have start points and end points, whereas GAD you really think of as that constitutive background state of anxiety. What we do know is that the longer that someone has high anxiety, the more likely they are to have a major depressive episode.

The more major depressive episodes and the more severe major depressive episodes people have, the more likely they are to have high levels of anxiety in the background. When we think about probability of success, it's a really interesting question. Historically, MDD has been an easier target for all classes of antidepressants than GAD with those same antidepressants. In part, that's due to the fact that we're in the case of MDD, helping folks go to a state that they were in if not recently, at least fairly recently in the last, you know, year or two years at the most, and often much more recently than that.

It's more like resetting a state that the person will get back to and has been in more recently, whereas GAD is more of a change to a state that someone probably hasn't been in in quite some time because of the longitudinal nature of the disease. MDD has historically been an easier target and that in part is what gives us great confidence. We also, of course, saw in phase II that we were able to move the MADRS pretty dramatically in the GAD patients we were treating, despite the fact that they were starting lower than we would ordinarily start people in an MDD study. Which means, of course, there's less room on the scale to move in, and we still saw quite a bit of movement.

All of that together continues to give us real confidence in our MDD studies. As for placebo and GAD, probably that's not what's at play here. I think that as Rob spoke to already here and as we talk about kind of often, the design of that study both led to a higher actual placebo response with five arms or active, and the likelihood of getting drug being so high will drive an actual higher placebo response. Particularly 'cause there are these lower dose arms that may or may not feel like something to someone, so people on placebo could very easily mistakenly think they were on drug.

Also with the dropout rate and the data replacement strategy, taking that already actual high placebo response and making the measured placebo response, actually overrepresent the background real placebo response. That's probably more causal than the disease state itself.

Thank you for that. Maybe if I could jump in quick with Matt. Matt, you made a comment there that you guys have shared before, can you just help us understand, we don't hear this much, 1% penetration of the TAM equals to about $2 billion. Can you help us understand how that TAM, how do you handle the overlap of MDD and GAD to get to that number? On the commercial side too, can you just help us, you know, remind us what the learnings are from the J-code implications for SPRAVATO and how that might have triggered sales? Thank you.

Sure. The 4.2 million patient number that I cite is, it includes any of those patients who have both. These are unique patients that we've identified. These are all patients 18 and over. That is the true TAM. We've taken into account any of the overlap. If they have a dual diagnosis, they are deduped. In regards to the J-code for SPRAVATO, I think what that does is it gives us good confidence that there's a path forward to submit for a J-code for DT120 as well. That's been in our plans and that's an operating assumption to submit once we get into market if DT120 is approved.

Thank you.

Thank you. One moment for our next question. Our next question comes from the line of Pete Stavropoulos of Cantor. Your line is now open.

Hi, this is Samantha on the line for Pete. Thanks for taking our questions, and congrats on the quarter. For the MDD OLE, you set the trigger for redosing at a MADRS score of 20 or greater. Could you help us understand why 20 was chosen? Through your market research, is that level of severity a threshold where healthcare practitioners would likely recommend to patients another dosing session?

Yeah. Thanks so much. I'll turn it over to Dan as well.

Yeah, great question, Samantha. Across our studies, what we've decided to do in the part Bs is set the threshold on the scale at the line between mild and moderate. There are a couple. You know, obviously on all these scales, that's somewhat arbitrary, right? The scale designers pick numbers and those get psychometrically tested and validated, and those numbers become the thresholds for the life of the scale at some level.

We thought the threshold between mild and moderate was particularly interesting because, yeah, in talking to the wide community of prescribers and treaters out there, this certainly seems like the level at which people would consider even medication at all, let alone a, you know, more intensive and likely expensive medication. That threshold also corresponds with an interesting change, which is a little less scale-based, but the practical reality is that when we think about mild versus moderate illness, moderate is where people start to accumulate functional deficits, where the symptoms of the disorder become severe enough that they interfere with activities of life, activities of daily living, whether they're school, work, family, whatever.

That seemed to us to be the reasonable place to draw the line in the studies and a likely threshold that would be applied clinically, though by no means would it be a necessary threshold for clinicians to follow. Of course, in the end of the day, clinical judgment rules everything. These scales, because of their intensiveness of administration, are not often used in clinical practice. What we assume will happen with real prescribers based on the conversations we've had with those folks is that if in their assessment they assess someone to have functional deficits from their disorder, that will very much push them in the direction of using therapies like ours.

Great.

I'll add one bit of color there too, Sam, which is just that, you know, while there's a lot of discussion, of course, about the various sort of subsets of MDD and the, you know, the patient populations who have not previously responded to SRIs as being some sort of unique entity, the real thing we see, both in terms of patient experience and in terms of health economic outcomes, and all the things that actually drive benefit both personal and functionally and economically, is improving the severity.

Finding patients who have severe symptoms and improving those down to a state where that functional deficit is improved meaningfully. That's why we set the threshold for treatment there. It's also why we're so focused on looking at the severity of these populations rather than siloing ourselves into a small subset of the population that just didn't respond to two past SRIs.

Very clear. Thank you. If I can just sneak in one more question. With interventional psychiatry being increasingly integrated into practices and healthcare systems, what preparations are underway at clinics to pivot and deliver DT120 operationally? Maybe what are you hearing as you do your commercial prep work?

Matt, I'll turn it over to you.

Thanks, Sam, for the question. What we're hearing from clinicians, especially those that are doing high volumes of intervention today, is that they have been prepping for the psychedelics coming to market and that they're allocating space for that. We feel pretty encouraged by the anticipation and the receptivity of the market for these interventions as they make their way into market. Certainly there's a high anticipation for DT120 and some of the data that we shared just a couple of weeks ago, I think really highlights the momentum and the receptivity of the market.

We're encouraged by all those different facets and we believe that our targeting model really does help to prioritize those physicians who are, A, receptive to the drug concept and, B, have the capability and the capacity to accommodate these patients for treatment.

Thanks so much.

Thank you. One moment for our next question. Our next question comes on the line of Matthew Hershenhorn of Oppenheimer. Your line is now open.

Hey, guys. Congrats on all the progress. Thanks for taking our questions, and thanks again for hosting us two weeks ago at your event. Very insightful and really appreciate it. The question we had was just as you talk to clinics, what are some of the economic incentives they have to modify capacity for DT120, especially considering away from SPRAVATO? If you see time-based reimbursement and less friction arising from patient turnover compared to SPRAVATO as potential advantages, and perhaps if you have any estimate on how many clinics it would take to eventually treat 100,000 patients per year, just considering likely capacity, we'd really appreciate it. Thank you.

Yeah. Thanks for the question. You know, regarding the practice economics, certainly we recognize that that's top of mind for physicians, and we are in the process of building out clear direction on what will be available at launch and also those codes that we want to secure post-launch, make sure that physicians are adequately reimbursed for the administration. I think the way that the clinics have been thinking about this, at least early on, has been to allocate certain amount of space, and then their anticipation is to judge the market and judge the volumes that are coming in to determine whether they need to allocate additional space to their clinics. You know, this is something that's really gonna be determined as we get into market.

As we get closer, we'll have a lot more market research to share on what we think that volume and capacity will be, both in market and then in downstream, in years thereafter.

Got it. Thank you so much. One additional question quickly was just on PTSD, if you could please talk about any differentiated advantages for DT120 just compared to the other psychedelics, psilocybin and DMT, specifically for this indication, just thinking of the various symptoms there. If you have any input or discussions with the VA, just considering the prevalence amongst veterans there, informing enrollment criteria or any data collection that they could potentially be interested in, would definitely appreciate it. Thanks again.

Thanks so much, Matt. Dan, you wanna take that one?

Yeah, happy to. There we go. Off mute. One of the things that we hear from sites quite a bit about the characteristics of DT120 and the patient experience with DT120 is that it is very well tolerated, particularly emotionally. That people find the onset of the drug, its action, while it's at its sort of plateau effect, and then the gentle return to a normal state of consciousness to be tolerated well and also to be pleasant in ways that other drugs may not be. Particularly with folks with, you know, high levels of anxious arousal, that's probably a good thing, right?

That we want folks who are particularly attuned to their surroundings and attuned to that sort of hypervigilance that happens with PTSD to have that sort of experience, to have a predictable and gentle experience that allows them both the time to have the experience that they're having while they're at the plateau, but also to have that predictable onset and offset. We think that really is a differentiated advantage of the drug itself.

Got it. Really helpful. Thank you guys again. Appreciate it.

You know, I what I didn't say was the second half there about the VA and, you know, we've been working.

Oh, please.

Yeah. We've been working with VA researchers on our research to date. Of course, as we move into the world of PTSD, we will continue to deepen and strengthen those relationships. Of course, we're continually seeking advice from experts across the different conditions we work with. The VA expertise in PTSD will be really important to the design and execution of those studies as it has been in our studies to date.

Perfect. Thank you so much for addressing that. Thanks again, guys.

Thank you. One moment for our next question. Our next question comes from the line of Sumant Kulkarni of Canaccord Genuity. Your line is now open.

Good afternoon. Thanks for taking our questions. I have three. First, what are your latest thoughts on a filing strategy? Will you file both GAD and MDD at the same time, or do you think GAD, which will have two phase III readouts earlier, will be your first targeted indication? That's the first question.

Yeah. Thanks, Sumant. You know, obviously we're having a lot of discussions with FDA and have been around that appropriate strategy. I think what we've of course have seen also a lot coming out of FDA about thinking for filing on studies where there is a high degree of overlap. There's a long regulatory and legal precedent when there are highly overlapping indications for a single study to be supportive of expansion into that indication. You know, obviously some of that's gonna be contingent on how compelling data are across the studies and particularly in MDD, right?

If we see a smaller effect, I think obviously we have less compelling evidence than if there's an extraordinarily large effect that we're observing that would imply, you know, quite small studies needed to replicate that. Some of it's gonna be ultimately informed by the data and subsequent discussions with FDA, but we feel quite confident in the position for filing DT120. Regardless of whether that's filed concurrently or sequentially, we think we'll be in a great position to go after both these markets hopefully, as we get in the market and get into the patient population if we're fortunate enough to get a drug approved.

Got it. Thanks. Second, for Matt on commercialization, both GAD and MDD present very large opportunities, but which one do you think could prove more challenging to crack for DT120 and why?

Thanks, Sumant. Look, we feel like the unmet needs for both these indications are high, and there is great receptivity in our market research for both indications. Our targeting model, our value proposition is really aimed at both indications. You know, we don't have a favorite. We do believe that there are a lot of patients out there that need help and need this treatment. If approved, we believe that we're going after both markets should we have a dual indication with equal measure. Keep in mind too that the diagnosis of GAD is not as reflective in the claims data as MDD simply because there haven't been any novel treatments in a couple decades.

We do believe that there's a lot of GAD out there that isn't adequately diagnosed in the ICD-10 data. We believe that that will also change with therapeutic intervention that meets that need.

All right. Last one is almost perhaps a philosophical question. What are the real world advantages and disadvantages of receiving a commissioner's national priority voucher?

Yeah. Thanks, Sumant. It's a good question, one, you know, I think obviously anything that we can do to accelerate and be more efficient in development, we certainly are interested in entertaining. That's why we've been going at a really lightning speed, and we opened this IND in like less than about four years ago. We've been going at an incredible pace of development. Those are the things that we can of course control and, you know, put in all the time and effort and do the research the right way to move program forward to pivotal data, which we have coming up very soon. What comes after that, obviously with novel programs with FDA, there certainly can be advantages. There's also potential risks.

I think one thing that's particularly, you know, important for our program too is this opportunity to potentially go after both of these indications. If we're in that position, you know, I think there's a lot being navigated in terms of which both one or the other would potentially benefit from something like a CMPV. You know, we've of course seen some positives come out of that. We've seen some risks associated with that. We're gonna keep with our great dialogue with FDA and continue to look for opportunities to accelerate anywhere we can. Right now, getting the data and going as efficiently from there to towards an NDA application is where we're focused.

Thank you.

Thank you. One moment for our next question. Our next question comes from the line of Chris Chen of Baird. Your line is now open.

Hey, everyone. Thanks for taking my question, and congrats on the progress. Just regarding the Emerge readout, I'm just curious how granular your patient time to discharge data will be? If you do go slightly over, you know, that eight-hour window, is it still possible to still secure a label with an eight-hour treatment window? Thanks.

Yeah. Thanks, Chris. We are extremely detail-oriented in everything we do and try to get really precise definition of all of the important characteristics of these studies. We'll do the same in terms of how we, you know, have been doing analyzing the end-of-study checklist and when patients can be cleared for monitoring. Of course, those dynamics, we'll be looking at everything from, you know, means to side effects to individual patients and anything that could be useful there. You know, it's going to be something that we're quite interested in, and we feel, you know, quite excited about being able to present some data from.

Thank you. One moment for our next question. Our next question comes from the line of Patrick Trucchio of H.C. Wainwright & Co. Your line is now open.

Hi, it's Arabella on for Patrick. Thank you so much for taking the question. I guess now that DEA rescheduling can be done after a successful phase III, how much time is that realistically actually going to save? I guess, how are you thinking about initiating those conversations once you get the data? I was also just wondering if you could comment on DT402 in ASD, and what kind of metrics or signals that you're looking for to move the program forward. Thank you.

Thanks, Arabella. I think you're referring to the executive order that President Trump signed indicating the DEA should look at their scheduling assessment after phase III data, not after FDA approval. If that were to be implemented directly and DEA could, as a result, make a decision on scheduling at the same time of an NDA approval, that could save, you know, 90 days, which is the timeline right now to get to an interim final rule and an issuance of the schedule for the approved product.

There's a real opportunity and something we've been actually quite engaged with for a while, exploring opportunities to not shortcut anything, but to streamline the process and enhance the collaboration across agencies within the federal government to make that timeline from FDA approval to patients actually getting access to the drug as short as possible. With such a huge need and such an opportunity to address that need, we shouldn't be waiting any days that we don't have to get these drugs to patients. We're quite excited about that opportunity and continue to have great dialogue with FDA, with CSS at FDA and whenever we are able to with DEA.

To your second question, I'll turn it over to Dan to briefly touch on DT402.

Yeah. Thanks for asking about DT402. We'd love to get a chance to talk about it. As we've said before, we're doing a pretty interesting signal of efficacy study in ASD. In order to do that across the course of a day, we've combined a set of measures that we're able to do repeatedly through the day, right? To look at the dynamics of pre-dose, early in the dosing experience, late in the dosing experience, again, as the drug wears off.

To do that, we've constructed what might be a little bit skinnier instruments than you'd ordinarily use for regulatory approach, but that have the components of those, you know, the construct components of those instruments that can be asked reasonably quickly and repeatedly through the day. We've got patient-reported outcomes, we've got clinician observation outcomes, caregiver observation outcomes, and some digital markers, some sort of novel digital behavioral markers that look at things like voice and facial expression and eye tracking, all rolled into what is a pretty dense day of dosing with as many different measures as we could comfortably for the patient experience fit into that dosing day.

Thank you. One moment for our next question. Our next question comes from the line of Ami Fadia of Needham & Company.

Hi. Good afternoon. Thanks for taking my question. How much data do you need from the part B of the studies where you're examining how long it takes for patients to, you know, take that second or third or fourth dose before you submit for approval and to be able to, you know, inform the circumstances of retreatment in the label? Also, how much data do you think you need to have the conversations with payers around, you know, coverage and pricing? A second question is just with regards to the capacity in the market with the number of clinics that are out there today.

In order to really achieve sort of the peak potential, how much expansion do you think there needs to be in terms of the number of clinics that are equipped to treat with psychedelics in the U.S., and what's sort of the timeframe or what are some bottlenecks that you think exist in order to, you know, see that type of expansion? Thank you.

Yeah. Thanks so much, Ami. Yeah, we're absolutely, you know, confident in our position as we approach top-line data and getting the data from part A. It's worth just pointing, you know, pointing out briefly that in precedent drug approvals, particularly with antidepressants where we have a lot of precedents, most of those drugs are approved on acute studies with post-marketing commitments to conduct longer-term chronic studies. We are pushing the bounds of what an acute study can do in this way. A single dose, we're following patients for 12 weeks and GAD, a primary endpoint at that 12 weeks, which is, you know, patients with GAD do not spontaneously have 12 weeks of significant improvement.

That approach is one of the important components of what drives our confidence in being in a great position with the part A data. Of course, the part B data will be useful to inform intervals for retreatment and sort of over time retreatment patterns, what happens upon subsequent retreatment, all the things we're trying to characterize there. We already have quite a bit of that part B data, and we'll continue to aggregate that across all of our programs throughout the, you know, the remainder of this year and as we continue to progress towards NDA filing.

In terms of capacity, you know, we think that this is something that is significantly underappreciated by a lot of folks, which is that the capacity that exists today is really far in excess, I think what any of the models that are out there projects for adoption. We do not see a sort of capacity constraint. One of the things for those of you who were in attendance in New York a few weeks ago with us, is to bring a little bit of clarity and sort of demystify what it actually means to set up a treatment room.

If you have a room and a site that is willing to spend a few hundred dollars on making it a little bit more comfortable, that might be better for patients. If you have a room that someone can be for an extended period of time, in a current treatment facility, that's enough. We do not see that there being a substantial financial or sort of logistical bottleneck. People use the term infrastructure, though, that's far too heavy-handed of a word. You know, we think there's plenty of capacity today.

There will, we expect, be a lot more capacity growth over time and with what we intend to do, which is provide the best support to the patients and providers out in the field so that they can adopt and get treatment if they so desire. You know, we think there'll be a great incentive and a great desire to adopt both treatment centers and, you know, for patients to come in for treatment.

Thank you. This concludes the question and answer session. I'll now turn it back to CEO, Rob Barrow, for closing remarks.

Okay. Well, thank you everyone for joining us today. We're very excited about the quarters ahead with three pivotal readouts anticipated across the second and third quarter. We'll look forward to sharing those data in due course. Thank you all.

Thank you for your participation in today's conference. This is a concluded program. You may now disconnect.

Good afternoon, and welcome to the Definium Therapeutics Full Year 2025 Financial Results and Business Update Webcast. [Operator Instructions] The webcast is live on the Investor and Media section of the Definium website at definiumtx.com, and a replay will be available after the webcast. I would now like to introduce Gita Jain, Head of Investor Relations of Definium. Please go ahead.

Thank you, operator, and good afternoon, everyone. Thank you for joining us today for a discussion of Definium's full year 2025 financial results and business update. Leading the call today will be Rob Barrow, our Chief Executive Officer, who is joined by Dr. Dan Karlin, our Chief Medical Officer; Brandi Roberts, our Chief Financial Officer; and Matt Wiley, our Chief Commercial Officer. An audio recording and webcast replay for today's conference call will also be available online as detailed in the press release announcement for this call. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, efficacy and regulatory and clinical progress of our product candidates, our anticipated cash runway and our future expectations, plans, partnerships and prospects. These statements are subject to various risks such as changes in market conditions and difficulties associated with research and development and regulatory approval processes. These and other risk factors are described in the filings made with the SEC and applicable Canadian securities regulators, including our annual report on Form 10-K filed today. Forward-looking statements are based on the assumptions, opinions and estimates of management at the date the statements are made, including the nonoccurrence of the risks and uncertainties that are described in the filings made with the SEC and the applicable Canadian securities regulators or other significant events occurring outside of Definium's normal course of business. You are cautioned not to place undue reliance on these forward-looking statements, which are made as of today, February 26, 2026. Definium disclaims any obligation to update such statements even if management's views change, except as required by law. With that, let me turn the call over to Rob.

Thank you, Gita, and thank you, everyone, for joining our call today. We are incredibly excited to share today's updates as we rapidly approach our anticipated pivotal readouts for lysergide tartrate or DT120 ODT in generalized anxiety disorder and major depressive disorder in the months ahead. The momentum is palpable both across our development programs and in the world of psychiatry as we prepare for the adoption of psychedelics as potentially transformative new treatment options. We continue to believe in the potential of DT120 ODT as a best-in-class product candidate. And over the past year, our team has yet again set the standards for scientific rigor, efficiency and thoughtfulness and execution. As I reflect on 2025, I could not be prouder of our team and the progress we have made. Over the course of the last year, we rapidly progressed our late-stage pipeline, significantly strengthened our balance sheet and continued to expand our world-class leadership team and Board of Directors to drive our next phase of growth. Through ongoing engagement with the FDA under the breakthrough therapy designation program, we reached alignment on many key aspects of our development and submission strategy, positioning us to maximize the speed and efficiency of our NDA submission for DT120 ODT, subject to positive trial readouts later this year. Our commercial strategy and organizational readiness have mirrored these R&D successes with the addition of key commercial leadership led by Matt Wiley, who joined as our Chief Commercial Officer in March 2025. We've seen strong engagement across the spectrum, positioning us to deliver on our aim to yet again define the standard of excellence in the adoption of psychedelics. We began 2026 with the launch of Definium Therapeutics, a refreshed brand that reflects the evolution of our company and our leadership in psychiatry. Our differentiated strategy grounded in disciplined execution, scientific rigor and an ambitious view of the impact we can drive positions us to develop scalable, accessible treatments and drive long-term value for our shareholders. With 3 Phase III readouts expected in 2026, the first of which is just months away, we expect the year ahead to be a pivotal one, both for Definium and psychiatry at large. Our goal is clear: to address the urgent need for a new class of drugs that can offer meaningful relief to the millions of people who are living with GAD and MDD, disorders that have long been underserved by treatments with high burden, moderate efficacy and often poor tolerability. Building on our strong dose optimization Phase IIb study, which was published in JAMA last September, our clinical program for DT120 ODT consists of 4 pivotal Phase III studies, 2 in GAD, the Voyage and Panorama studies, and 2 in MDD, the Emerge and Ascend studies. I'm pleased to share today that Emerge, our first pivotal study in MDD, is fully enrolled, and we anticipate delivering top line data in late Q2. And while Emerge is the last of our 3 ongoing pivotal studies to be initiated, we could not be more excited to share this readout first across our Phase III programs. This sequencing both provides the opportunity to establish evidence in a second major market indication and enables us to engage with FDA with ample time to explore potential opportunities for accelerating our regulatory submission strategy for the MDD and GAD indications. We've also made significant progress in launching Ascend, our second pivotal study in MDD. Our first sites in Ascend have been activated, and we anticipate first participant dosing by early Q2. On to our GAD program, we continue to see strong enrollment across Voyage and Panorama. Enrollment in Voyage is approximately 80% complete. And based on the enrollment rate in current queue of patients, we expect to conclude enrollment in the coming weeks with top line data expected in early Q3. I'm also happy to share that with the preplanned blinded sample size re-estimation is complete with no required increase in sample size. Dan will be sharing further details on the sample size re-estimation in a few moments. Enrollment in Panorama, our second Phase III study in GAD is rapidly progressing, and we remain on track to deliver top line data in the second half of 2026. We plan to provide a further enrollment update and to disclose the outcome of the Panorama blinded sample size re-estimation at our Investor and Analyst Day in April. Our team remains focused on delivering high-quality data across our Phase III studies, targeting 2 of the largest and most impactful indications in psychiatry. We continue to believe in the best-in-class potential of DT120 ODT and are dedicated to the scientific rigor and disciplined execution that has defined our organization and successes to date. With that, I'll turn the call over to Dan to share additional details on our clinical programs.

Thanks, Rob. We remain highly encouraged by the enrollment trends we are seeing across our Phase III GAD and MDD studies. We've been spending a lot of time with our sites and investigators, and there is a high degree of excitement and engagement as we get closer to delivering top line data. As Rob mentioned, we are especially excited to deliver Emerge as our first pivotal readout in late Q2. While our Phase II Montgomery-Asberg Depression Rating Scale, or MADRS, results in GAD have given us great clinical confidence through the design and execution of Emerge, we have not previously had the opportunity to establish the efficacy of DT120 in a dedicated MDD population with patients in a major depressive episode. While GAD and MDD are substantially overlapping disorders, MDD is defined as an episodic illness with periods of euthymia or normal mood interrupted by major depressive episodes, which are characterized by dysthymia or depressed mood that must persist for at least 2 weeks and may last many months. GAD describes and is defined by a more continuous state of heightened anxiety. In our GAD program, starting with Phase IIb, we demonstrated DT120's remarkable ability to improve this continuous background condition, while our MDD program is intended to demonstrate the same effect on the course of major depressive episodes. Taken together, these data suggest that if approved, DT120 may represent a data-driven evidence-based clinical choice for providers and patients with the potential to improve patient outcomes, whether the patient is currently in a major depressive episode or not. Each of our 4 pivotal studies across GAD and MDD is comprised of 2 parts. Part A, a 12-week randomized, double-blind, placebo-controlled parallel group period, assessing the safety and efficacy of a single dose of DT120 ODT versus placebo, and Part B, a 40-week extension period with opportunities for open-label treatment. The primary endpoint in our MDD studies is the change from baseline in MADRS score at week 6 between DT120 ODT 100 micrograms and placebo. The MDD trials were designed with 80% powered to detect a 5-point improvement over placebo on this endpoint. The primary endpoint in our GAD studies is the change from baseline in the Hamilton Anxiety Scale, or HAM-A, at week 12 between DT120 ODT 100 micrograms and placebo. The GAD trials were designed to have 90% powered to detect a 5-point improvement over placebo on this endpoint. Our Phase III studies are modeled after our successful Phase IIb study in which we observed placebo-adjusted improvements of 7.7 points on the HAM-A and 6.4 points on the MADRS at week 12. In the context of other approved pharmacotherapies, which have typically shown a placebo-adjusted effect of less than 4 points on these endpoints, we believe DT120 has the potential to be not only a best-in-class product among psychedelics, but among anxiolytics and antidepressants broadly. And while placebo-adjusted changes are critically important for establishing efficacy, the absolute magnitude of improvement may be a more representative measure of the real-world patient experience. This is where DT120 even further stood out, having demonstrated a 21.9 point absolute reduction in HAM-A scores at week 12, corresponding with a 48% clinical remission rate and a 65% response rate. In addressing comorbid depressive symptoms, we saw an 18.7-point absolute reduction in MADRS scores at week 12. I'll now recap progress with our MDD studies. Enrollment is complete, and we expect to deliver top line data from Emerge in late Q2. Based on the progress in Emerge, we are moving forward with the execution of our second pivotal MDD study, Ascend. In Ascend, we are targeting enrollment of approximately 175 participants randomized 2:1:2 to receive DT120 ODT 100 micrograms, 50 micrograms or placebo. Our first sites in Ascend have been activated, and we expect to begin dosing by early Q2. We expect Ascend to continue to benefit from operational efficiencies that enabled the rapid enrollment of Emerge, including the ability to fast track select sites that participated in Emerge and those that are actively enrolling in our GAD program. Regarding our GAD program, we are in the final stages of enrollment in Voyage with completion anticipated in the coming weeks. In Voyage, we are targeting enrollment of approximately 200 participants randomized 1:1 to DT120 ODT 100 micrograms or placebo, while in Panorama, we are targeting enrollment of 250 participants randomized 2:1:2 to DT120 ODT 100 micrograms, 50 micrograms or placebo. Each GAD study includes a sample size re-estimation that allows for adjustment of the target enrollment based on a blinded evaluation of nuisance parameters. As Rob mentioned previously, we completed the sample size re-estimation for Voyage and determined that no increase in the trial sample size is required. In the initial study power calculation, we assumed a standard deviation of 10 points and a non-evaluable rate of 15% at week 12. Among the first 100 participants who completed week 12, we saw a model-based standard deviation of 6.7 points on the HAM-A and a non-evaluable rate of 10%. These observations suggest that the study's ability to detect a statistically significant drug effect substantially exceeds the planned power. In fact, if these nuisance parameters were to remain unchanged from the final analysis, this would imply that the study has over 99% power to detect a 5-point difference on the HAM-A and that the minimum difference required to achieve statistical significance would be less than 2 points. Beyond DT120, we are excited to have initiated our Phase II study of DT402 in autism spectrum disorder, or ASD, in late 2025. DT402, the R enantiomer of MDMA, has shown promising prosocial effects with a potentially favorable tolerability profile. We're developing DT402 to target the core symptoms of ASD, specifically addressing social communication that is central to the experience of the disorder. We believe this program represents another significant treatment opportunity given the high unmet need, the increasing prevalence of ASD and no FDA-approved therapies that specifically address these core symptoms. Having completed a Phase I single-ascending dose study that characterized the tolerability, pharmacokinetics and pharmacodynamics of DT402 in healthy adult volunteers, we dosed the first participant in our Phase IIa study and initial data is expected later this year. This study is a single-dose open-label design, assessing early signals of efficacy in up to 20 adult participants with ASD. The objectives and endpoints of the study are designed to characterize the pharmacodynamics and clinical effects of DT402 across multiple functional domains. Across our late-stage pipeline, we are making strong progress and rapidly approaching multiple pivotal readouts for our DT120 ODT program. We believe the remarkable profile of DT120 has the potential to be best-in-class among GAD and MDD pharmacotherapies, and we are confident in our strategy and execution to drive the broadest possible impact for the millions of patients in need. Now I'll turn it over to Matt for commercial comments on DT120.

Thanks, Dan. As an organization, we are deeply committed to and focused on impeccable commercial readiness for the potential launches in GAD and MDD. Over the past year, we've comprehensively mapped the provider landscape nationwide, and in close collaboration with our cross-functional internal teams, prioritized key states for launch. If approved, we are fully positioned to execute rapidly and with precision. Our vision for Definium commercialization is to deliver a genuinely high-touch white glove experience for our providers, one that extends the collaborative partnership-oriented approach that has distinguished us throughout our clinical development and with our trial sites. This philosophy has been a key differentiator for us, and we intend to make it a foundational element of our commercial model. We fully appreciate that providers will have multifaceted needs beyond just product information. They will seek clear guidance on REMS certification, regulatory requirements, operational integration and reimbursement pathways. Accordingly, we are building the robust infrastructure and cross-functional teams required to address these elements seamlessly and support providers from day 1. To strengthen our launch capabilities, we've assembled an exceptional commercial leadership team over the past year in marketing, market access and operations. This leadership team comes with deep experience in navigating complex launches, including experience with REMS and scheduled drugs. Their proven track record gives us tremendous confidence as we prepare for launch. We look forward to sharing more detail on our commercialization strategy at our upcoming Analyst Day on April 22. But stepping back, our message is simple. We are preparing to introduce something meaningfully different. Historically, when new classes of medicines have been introduced in psychiatry, they have generated significant value and delivered multibillion-dollar opportunities. We believe DT120 has the potential not only to participate in that kind of opportunity, but to improve on what has come before, most importantly, for patients who urgently need more than better. With that, I'll turn our call over to Brandi to discuss our full year 2025 results. Brandi?

Thanks, Matt. Research and development expenses were $117.7 million for the year ended December 31, 2025, compared to $65.3 million for the year ended December 31, 2024, representing an increase of $52.4 million. This increase was primarily driven by $44.7 million in higher DT120 program expenses, $9.3 million in internal personnel costs, reflecting expanded research and development capabilities, and $0.4 million in preclinical and other program expenses, partially offset by a $2 million reduction in DT402 program expenses. General and administrative expenses were $48.6 million for the year ended December 31, 2025, compared to $38.6 million for the year ended December 31, 2024, an increase of $10 million. The increase was primarily attributable to $6 million in professional services and pre-commercialization activities, $3.6 million in personnel-related expenses to support expanded operational activities, $0.7 million in directors' deferred share unit expense driven by our year-over-year stock price appreciation, and $0.5 million in other administrative expenses, partially offset by a $0.8 million reduction in legal and patent-related expenses. Overall, our R&D and G&A expenses for 2025 were in line with our internal expectations as we continue to make significant progress across the DT120 and DT402 programs. Net loss for the year ended December 31, 2025, was $183.8 million compared to $108.7 million for the year ended December 31, 2024. As a reminder, our net loss can be significantly impacted by changes in the fair value of our 2022 USD financing warrants. During 2025, the change in fair value was $22.8 million, reflecting an increase in our stock price from $6.96 at December 31, 2024, to $13.39 at December 31, 2025. We ended 2025 with cash, cash equivalents and investments of $411.6 million compared to $273.7 million at year-end 2024. Based on our current operating plan and anticipated milestones, we believe our cash, cash equivalents and investments as of December 31, 2025, will be sufficient to fund operations into 2028. We are pleased to enter 2026 with the financial flexibility to accelerate several key initiatives, including NDA preparation, market access priority activities, market research and KOL education. These investments are intended to support our path to market, and if DT120 ODT is approved, enable a well-prepared and robust commercial launch. We are also encouraged by the continued evolution of our investor base with strong engagement from existing shareholders and growing interest from new investors as we progress through 2025. As we look ahead to a very important year in 2026, our focus remains on disciplined execution, thoughtful capital allocation and advancing our programs in a way that supports long-term value creation. I'll now turn the call back to Rob for our closing remarks.

Thank you, Brandi. 2025 was a year of bold ambition and disciplined execution. In 2026, Definium is set to deliver some of psychiatry's most important data, highlighting our progress and ambition to bring novel scalable therapies to patients underserved by today's standard of care. With a strong balance sheet and a late-stage pipeline with multiple catalysts in the months ahead, we're excited to continue driving value for our shareholders and the millions of patients who deserve more than better. Of course, none of this progress will be possible without our exceptional team whose passion, commitment and unmatched execution continue to set the standard for our field. Thank you again for joining our call today. We will now open the line for questions.

[Operator Instructions] Our first question coming from the line of Andrew Tsai with Jefferies.

For this interim that you did, it's very interesting for Voyage. I'm curious in the hypothetical scenario where the DMC asked or recommended you to upsize the trial, what would have been effectively the placebo-adjusted delta for that to happen, give or take? And just to confirm, there were no other scenarios with this interim such as stopping for futility or even stopping for success?

Yes. Thanks so much for the question, Andrew. So this is -- first of all, it was a blinded sample size re-estimation. And so an important feature of that analysis is that we don't ever unblind the study. We don't do any inferential testing. And as a result, we don't actually learn anything about the performance of the 2 groups independently or in relation to one another. Effectively, you can think of it as looking at the right side, right of the plus or minus on the 95% confidence interval to assess the standard error and ensure that the assumptions we made at the beginning of the study are reflected or we don't lose power because we've made the wrong assumptions. And so there was no implication. There's no learnings or inference that can be derived either from this analysis or for any other outcome of the analysis. But we are certainly excited to see that we're good with the assumptions we made. And if anything, as Dan mentioned during the call, have certainly adequate power at 99% or greater if the current variables hold, nuisance parameters hold. And we're eager to get to the study results and ultimately do that inferential test and look at the performance of 120 versus placebo.

Wow. Okay. And then really quickly, by the time you top line the Voyage data now in early Q3, would you consider piecemealing some of the Part B open-label extension data just to further showcase how durable a single dose of 120 could be? Otherwise, when would you share the open-label portion?

Yes, absolutely. I think one of the things we've been really focused on is, of course, the durability and the response patterns over the course of an entire year. And of course, in all of the studies have been running for quite a while now. And so as we continue to accrue patients who have gone through certain milestones and either events of retreatment or have made it through a fixed interval of time, we'll have, of course, increasing data and increasing confidence in those data to be able to share some insights. So we haven't firmed up a commitment to exactly when we would present Part B data. So we certainly don't want to get ahead of ourselves, and we present data that we don't feel are representative or that we're not confident in at any time. So we'll certainly be taking a look at that. And as we accrue those data, be it at any of the readouts from the ongoing studies or at another time, we'll have an opportunity to share as much insights as we possibly can about the performance in Part A and Part B.

Our next question coming from the line of Mark Goodman with Leerink.

This is Basma on for Mark. Our first question is on the interim look. Again, have you conducted the interim look for Panorama as well or not yet? And -- or are you planning to do it once you hit 80% enrollment similar to Voyage? And also regarding the MDD, when are you going to plan to do the interim look exactly for the Emerge trial? Our second question is for the GAD readout. What are your expectations regarding the remission rate? What would you consider as a good and differentiated rate versus the standard of care? That's it for us.

Yes. Thanks so much, Basma. So in terms of the interim analysis for Voyage, we, of course, announced that today. For Panorama, our second pivotal study in GAD, we'll be sharing additional details and enrollment updates at our Analyst Day in April. For the 2 MDD studies, of course, Emerge is now fully enrolled and the data -- top line data that we'd be sharing would be the completed final top line analysis from that study. So we're not conducting an interim look on either of the MDD studies as currently. In terms of GAD and the remission rate, I'll turn it over to Dan to maybe comment about our thinking around response patterns and ultimately what drives patient experience and value in this population.

Yes. It's a great question about the remission rate because we've obviously talked about that from our Phase IIb outcomes. I think it's important to note that mostly what we know about pharmacotherapy-induced remission rate come from MDD studies. And in MDD, what we see in SRIs, the first-line treatment that's most commonly used, attributable remission rate in the real world is something in the 10% to 30% range. But of course, it's difficult to necessarily interpret those data because MDD is necessarily a cyclical illness so that when a major depressive episode is resolved, whether with meds or without, then that is a period of remission from those symptoms. We made some design choices in Phase III for both GAD and MDD, which was to target open-label treatment of the Part B treatments to the threshold between mild and moderate illness on the scales on the HAM-A and the MADRS. So in this case, what we are really looking at is given the availability of open-label treatment in the Part B, are we able to treat people down into that mild or better range reliably with the redosing. So while we're not priority specifying what we would hope for from an absolute remission rate, what we're intending here to do is to get people out of moderate or worse illness and see how well we can keep them in mild or better.

Our next question coming from the line of Evie [indiscernible] with Evercore ISI.

You have Evie on for Gavin. Congratulations on all the progress made this year. It's great to see that the SSRE is now complete. Any color you could provide on enrollment and how it is trending for the second GAD and MDD trial seeing as Voyage data is now expected by early 3Q? And our second question is in addition to the SSRE and variability, can you speak to anything else giving you incremental confidence? Could be something like baseline characteristics, OLE rollover, retention, screen failures or anything like that?

Yes. Thanks so much for the question. So in terms of enrollment updates, of course, with Emerge, our first MDD study now fully enrolled and with data expected in late Q2, we've just been overwhelmed by how fast we're able to enroll that study and how excited we think that represents the field and the researchers who are working on the study have been and are about the potential here. We certainly are, and our team has done an incredible job at executing on these studies. In terms of Voyage, we shared that approximately 80% enrollment, and we continue to see incredibly strong enrollment with our best months yet and we absolutely are seeing the continued growth and acceleration of enrollment across the program. So for our second study for Panorama, again, we'll be sharing further updates at our Analyst Day in April, but we've been encouraged across the board and really happy with where we are in enrollment in that study. Ascend, we're also, of course, will be starting in the coming weeks. We're really excited to get studies activated really faster than I think even we anticipated and the ability to get studies DEA activated and DEA approvals in place in a matter of just a few weeks has allowed us to really accelerate the start of that second study in MDD. So really across the board, we've been very encouraged by the enrollment trends and where that positions us for 3 pivotal readouts over the course of this year. In terms of incremental confidence, we won't be commenting on specific variables or what we're seeing in those variables. So we are extraordinarily confident in the profile of 120. And as Dan mentioned during his prepared remarks, with the observed parameters that we saw in the interim analysis for Voyage, that would imply a quite high, over 99% power to detect a 5-point difference and less than 2 points required in terms of the separation between the groups in order to achieve a statistically positive result if those nuisance variables are the same at the end of the study as they were at the interim analysis. So that gives us quite a bit of confidence if the study only has to show a couple of points difference to get a statistically positive outcome, of course, we would hope to see better than that. We think that a 4-point difference between the arms is something we'd really like to see that would really stand out as the best drug we've seen and the best results we've seen in GAD to date. And so we're certainly excited to deliver those data. But all that we're seeing across all of the studies gives us continued confidence in the program and positioning us really well for these readouts later in the year.

Our next question coming from the line of Brian Abrahams with RBC Capital Markets.

Congrats on all the progress and looking forward to a very exciting data rich year. Two for me. I guess, first, you've had some slight changes in the enrollment time lines versus prior expectations in both directions. And I guess I'm curious the impact that has on your views of the addressable populations of patients with these respective conditions who may be interested in a psychedelic. And then just with the interim passing and obviously, the low variability in dropouts, it sounds like a very narrow delta could still be statistically significant in Voyage. So can you maybe elaborate a little bit more on your latest views on clinically meaningful delta? And really how would hitting stat sig with a smaller delta potentially impact your plans in Panorama as well as how you'd see the drug positioned commercially?

Yes. Thanks so much, Brian. And both great questions. I'll turn it over to Dan to talk about the first one. And just Dan, maybe you can reflect on how we think about these populations and also how these patients, of course, show up in trials and show up for clinical attention.

Yes. It's an excellent question and a good observation. And while the time line changes don't necessarily change how we think about the patient population, certainly, what we know is that in the current environment of psychiatry with the drugs that are currently available, MDD has been a target of both drug development and clinical focus for really the last 30 years or so and left GAD a bit behind with no new drugs approved in GAD since 2007. The reality is that this is a massively overlapping patient population and that while GAD is a more continuous sort of background condition that people live with this experience day by day, and in many cases, for much of their life. And that both makes people not necessarily seek care. They're sort of used to being the way they are, even if it is quite disruptive to their lives. But it's not an acute change that people notice in their lives as they do when they enter a major depressive episode, which often drive people to seek care. So we're really excited about the opportunity to potentially provide a drug here that regardless of what induces someone to go seek care, whether it's this ongoing state of anxiety or newly developed anxiety or entering a major depressive episode, which represents a real state change for them. The way we think about this is that regardless of the driver of the presentation that we intend to provide a body of evidence that demonstrates that DT120 would be a good choice for the patient. So that gives us some temporal flexibility for people in the course of their lives and in the course of their illness.

Yes. Thanks, Dan. Brian, in terms of your second question about the clinical meaningfulness, it also is a great one. And I think really important contextually, both in terms of that difference and in terms of the overall magnitude of change. I think there is certainly a lot of different approaches out there to these concepts. In our minds, Dan mentioned this a little bit in the prepared remarks, but in the real world, patients, of course, don't get placebo. So while we definitely want to demonstrate as largely a placebo-adjusted response as we can, observing an absolute magnitude of change that stands out relative to the other options that are available, there are always limitations comparing across studies and such. But -- and we think that's an important variable to focus on as well. When it comes down to that placebo-adjusted change, again, when we're talking about drugs that we believe have the potential to be transformative, we think that should also be reflected in terms of the consistency with which patients are seeing the benefit and the magnitude of that benefit over placebo. And so while, yes, we're very encouraged when we have a low clinical bar relative to where we started and where we powered the study, we absolutely would like to see a change that stands out and continues to stand out as we saw in Phase II. And in GAD, when we look at the landscape of currently approved therapies, not one of them consistently delivers at or above a 4-point delta over placebo in those studies. And so if we're seeing a magnitude of change that's as large or larger than those and the placebo-adjusted change that's larger than 4 points, it's hard not to get incredibly excited about that in our mind. So while we don't set a sort of bright line on any of these kinds of concepts, we very much are looking for data that impress and data that get us and we think payers and providers and everyone excited about the potential because we certainly believe it's there and hope the data stands up to support that.

Our next question coming from the line of François Brisebois with LifeSci Capital.

A lot of interesting questions, a lot of interesting answers, too. And I was just wondering, so you touched on the 4-point kind of bar that is not a hard bar or anything, but something that you've been mentioning on the GAD side. Can you just remind us, now that MDD will be first, can you just kind of do the same exercise in terms of what you'd like to see and compare it to what's been seen for MDD? And maybe also remind everyone what you had seen previously on the MADRS side in the prior trial and maybe caveats around what you had seen because the trial wasn't necessarily for that originally.

Yes. Thanks so much for the question, Frank. I mean, again, when we look at the landscape of approved products and products that are in development, we continue to be encouraged qualitatively in the research we've done to date. Dan mentioned that we saw is in the GAD population with milder illness. I think we really focus a lot on the severity of both MDD and GAD because those severity are representative of impact on patients and drive a lot of the burden and the value. And so as we think about the response, we think about severity and that overall magnitude of change. And that's again where we saw really impressive results on both symptom sets, on anxiety symptoms and depression symptoms. So -- and we saw a 6.4-point difference between 120 and placebo in MADRS scores that was starting from a lower point than what we would expect in a dedicated MDD population of patients in a major depressive episode. We'll certainly be painting that picture, I think, more comprehensively as we get to the Analyst Day in April. And I think as we get closer and closer to the readouts, we want to set full context for those expectations and just the realities of that landscape. But when we look at -- roughly, when we look at that today, again, seeing an effect, a placebo-adjusted effect that is greater than 4 points seems quite important. And seeing a double-digit absolute magnitude of change also seems quite important in our minds. And that's true, especially in the MDD population where taking patients from severe depression symptoms to high, moderate or low severe wouldn't represent a major change in our minds. And so as we think about this readout, we again want to see a large absolute magnitude of change and as large of a placebo-adjusted change as the drug can deliver.

Okay. Maybe if I could sneak in just the last one there. In terms of -- when you do some work on it, you hear a lot of comments around, well, from going from the Phase II to Phase III, it's totally normal to get a smaller delta with placebo. Is that something that makes sense to people? Is there a reason behind that? Or is that just kind of protecting yourself a little bit?

Yes. No, I think the reality is that we certainly -- in historical studies in psychiatry, there are studies at times where that happens. I think where we see -- and we've seen this in schizophrenia, we've seen in a number of other indications as well, where some of the best-performing drugs continue to not see that sort of compression as they progress in development. And so the design changes, operational changes, those sorts of things can have an impact, and that's why we've been so encouraged with our approach in Phase III. And we designed our Phase II program to be exactly executed and designed like a Phase III study, although we thought it critically important to establish a dose response and select the appropriate dose to take into the pivotal studies, which is why we did the Phase II the way we did. That also means we made minuscule operational changes between the Phase II and Phase III study. So we're virtually doing the same thing over again is just with 2 or 3 arms instead of 5 arms as we did in Phase II. So that again gives us a lot of confidence. And then a number of dynamics in the study design that we think will drive better patient retention through the primary outcome in these studies. Dan mentioned that the non-evaluable rate that we saw in the interim analysis in Voyage was 10%. You compare that to over 25% in our Phase II data, which we think is largely driven by the fact that we're seeing with the Part B, the 9-month extension period, patients have an ability to access open-label 120 if they complete the full 12-week blinded control period. And so all of those dynamics give us a lot of confidence about the operationalization of these studies and give us a lot of confidence as we approach data.

Our next question coming from the line of Pete Stavropoulos with Cantor Fitzgerald.

Nice to see the progress. First one, just curious to hear how you're thinking about a potential filing strategy if the 2 GAD Phase IIIs are positive and if the first Phase III MDD study Emerge is positive, will you complete 2 MDD studies before filing an sNDA? Or is there a reason to wait for the second study?

Yes. Thanks so much for the question, Pete. It'd be premature to comment specifically on filing strategy given that we don't have data in hand. But certainly, we think that the stronger the data, the more compelling an argument that a sponsor can make, and that's true across the board. And so we'll be looking very closely at the data. And if we're seeing an impressive result, both placebo-adjusted and absolute magnitude of change, something that gets us quite excited, we will very much be engaging in those conversations to explore the most efficient pathway forward for both the indications.

Okay. And then just to touch on your earlier stage asset, 402. If you can give us a little bit of color in terms of assessing clinical effect, which scales are key for you? And in your deck and in the PR -- in today's PR, it mentions functional biomarkers. Can you just elaborate on that?

Yes, I'll turn that one over to Dan to comment on...

Yes. Happy to comment on that, and thanks for asking about 402. Obviously, with all the excitement around 120, sometimes we don't get a chance to comment on this as much as we'd like to because we're really excited about the program. We've gotten through a single-ascending dose safety study, which gives us good data for dosing in a single dose paradigm, which is exactly what we've said we've done, which is to bring the drug forward in a single dose open-label paradigm. And the question of measurement in ASD is always an interesting one. You're asking after the scales and the Vineland and other scales that have been used in attempts at approval before, of course, with no approved drugs for the core symptoms of the disorder, the right measure at the right time remains...

It sounds like a very narrow delta could still be statistically significant in Voyage. So can you maybe elaborate a little bit more on your latest views on clinically meaningful delta? And really how would hitting stat sig with a smaller delta potentially impact your plans in Panorama as well as how you'd see the drug positioned commercially?

Yes. Thanks so much, Brian. And both interaction, social communication and the other domains where we think that the drug will be effective. So considering measurement from the outset and very much thinking about measurement techniques that can track along with the drug through its phases of development and ultimately through to regulatory submission if we -- if and when we get there and potentially even measures that could travel with the drug out into the world if it's approved.

Congrats once again.

Our next question coming from the line of Christopher Chen with Baird.

Congrats on the progress. I had a question regarding MDD. So one of the things we hear about SPRAVATO is that it's good at alleviating symptoms of TRD, but not so good at increasing overall productivity of daily life, like just work -- productivity at work, one example. So I know you're measuring a number of quality of life metrics in Emerge, but I'm particularly interested in the WPAI. And so if you don't mind just expanding on your expectations there? And can you provide any high-level color on what you're hearing about how these patients are doing beyond just MDD symptom alleviation? And then I have one more after that.

Yes. Thanks, Chris. I'll turn it over to Dan to talk about WPAI. I guess I'd first say that with the dosing regimen that's required to go into a clinic for multiple hours, multiple or at least one time a week for a long time, being at work is certainly going to be a thing that drives productivity. So a treatment where you don't have to come in infrequently, which is if we're able to establish the same kind of durability as we've seen in trials so far, certainly something that we think would differentiate 120 from anything that's out there in the world today would be a pretty important impact, right? It's -- going to the doctor's office once or twice a week is quite a burden. And so even beyond the actual measurable productivity, the presence at work and being able to do that is going to be an important driver and certainly something that also shows up in patient satisfaction and overall utilization of the drug we would think. But I'll turn it over to Dan to elaborate maybe on the WPAI.

Yes. The domains that the WPAI look at absenteeism, not being able to make it work, presenteeism being impaired while at work and sort of tries to assess an overall percentage of impairment while at work. And of course, this isn't a primary outcome, and we're not looking to try to demonstrate efficacy overall based on a scale like this. But I think as you observed, this is really important, right, that just having a lower reported set of symptoms or suppressed symptoms doesn't necessarily mean that someone is back able to do the things that they need to do and want to do in their lives. And we very much are oriented toward the idea that just as we saw in Phase II that the experience of participants after treatment because, of course, unlike SPRAVATO, where the treatment is a continuous intermittent course, we anticipate having long periods of time between treatment if such retreatment is even always necessary. And the way that folks describe their experience post treatment in the Phase II was less about, as you're pointing out, sort of symptom suppression and more about having an outlook that was changed as it relates to the future of GAD, and obviously, as we hope to see in MDD as it relates to sort of the anhedonic or inability to take pleasure in activities that would generally give the person pleasure. So we are measuring WPAI and other scales of function and participation in life for exactly that reason because we remain optimistic and hopeful that the sort of change that we see with DT120 represents a more whole person change toward a state of what could be called recovery.

Great. That's very helpful. And then just a quick one. Are you collecting time to just -- patient time to discharge data in these trials? And if so, are you seeing anything that may suggest any shifts from that 6- to 8-hour monitoring period?

Yes, it's a great question. And we are absolutely collecting high granularity data. We think it's critically important to have data-driven arguments and a data-driven understanding of what's happening on a dosing day and to ultimately characterize that to inform regulatory discussions. We start assessing. We have a structured set of assessments that we measure on an hourly basis starting at hour 5. And we, of course, observe all patients regardless of the dose or whether they receive placebo through hour 8 in the study. And at the end of the day, we expect to have, again, a high granularity assessment of the different domains and ultimately, the time to which patients are able to be discharged safely, we think, from a treatment session. So we, of course -- given that we have a number of open-label treatment sessions, we have some insights there, which we can't share quite yet in great detail. We want to again aggregate enough data to feel confident in sharing that before we do so. But certainly, as we progress and as we get to a top line readout, we think it's really important given the nature of these drugs to start characterizing that, something we've been doing with a really thoughtful approach beginning with our Phase II study and certainly being refined and giving us increasing confidence as we've gotten through the conduct of a Phase III program.

Our next question coming from the line of Patrick Trucchio with H.C. Wainwright.

This is Arabella on for Patrick. Congrats on all the progress. We're looking forward to the upcoming readouts. Since Panorama also includes European sites, are there any meaningful differences in diagnostic practice, placebo behavior or standard of care that could introduce additional variability?

Yes, I'll turn that one over to Dan.

It's an excellent question and a good observation. The Panorama study does include European sites. And while there are, as you note, in the practice of psychiatry, regional variations even within the United States, different areas of the country have different practice patterns. And so the diagnostic criteria remain the same, the way they're applied can be different from place to place. We work our way through that by being very highly specified in our protocols. So diagnostic criteria that we use are standard from one country to the next and one site to the next, of course. And the way they're applied is standardized and that standardization is supervised and monitored from beyond the site level that all of our participants have really a 3-part confirmatory set of assessments, only one of which is based on the site assessment. We have central diagnostic confirmation and central severity confirmation so that it takes that kind of site variability out. Another advantage to the patient population is because we take both in the case of GAD, which as you know, as the European sites and MDD, which hasn't, because we aren't predicating enrollment in our studies on some set of past treatments or having been failed by some set of past treatments, local treatment pattern variation is not going to have an impact on who we bring into the trial. So we are incredibly confident that across sites here in the States and sites in Europe that we're getting the participants who we intend to get into the study. And because we're testing as a monotherapy, of course, we're getting participants independent of what might be local practice patterns for the treatment of these disorders.

Great. And then really quickly, I know we already touched on it, but specifically for GAD, and I know it's still early, if both Voyage and Panorama are positive, would that allow you to file? Or is there any additional long-term safety data or anything else that might gate submitting an NDA?

Of course, it's premature to talk finally about a filing strategy and filing dynamics until we had a final discussion with FDA at a pre-NDA meeting. But based on a really positive dialogue we've had with FDA throughout our pivotal programs, we feel highly encouraged that delivering Part A data, durability data out to 12 weeks is what we need for filing. And so as we get to top line data from these studies, we're already doing a ton of work to get ourselves ready to be in a position to file as quickly as possible and again, try to set that standard for how efficient and how quickly we can go to race across the finish line.

Our next question coming from the line of Ami Fadia with Needham & Company.

Congrats on all the progress. My question was on -- I have got 2. Firstly, just on the MDD program. You indicated that the study is 80% powered to show a 5-point change. And in your GAD study on MADRS, you've seen a 6.4-point change. What I want to understand is from a commercial perspective, in order to be able to tap into a meaningful portion of the MDD market, not just the really -- the patients that are treatment resistant, what type of a profile would you like to see? And then secondly, as you think about the regulatory landscape and how that's changing and the recent FDA stance on [Audio Gap]

[Audio Gap] and flexibility, although we are going to continue to hold ourselves to the highest standards of rigor. That all said, these are highly overlapping indications, and we are seeing, of course, and measuring symptoms of anxiety and symptoms of depression across all 4 of the studies. And so aggregating a large body of evidence if we're seeing consistent results across multiple studies across multiple domains with a high degree of both stand-alone and placebo-adjusted change. And the better the data are, the stronger the arguments are going to be whether it's 1, 2 or more studies for any program. And so we'll certainly take all of that into consideration and depending on the strength and the magnitude of responses that we're seeing across these studies, be in a position to chart a regulatory path forward there. To the first point, again, I think it's a little bit premature to talk overly precisely about segmentation about exactly where this would land in the commercial setting. I'll turn it over to Matt to maybe comment just how we think about that and the sort of expectations and hopes we would think about for both commercial adoption and for reimbursement as such.

Yes. Thanks, Rob, and thanks for the question. As it pertains to the patient profile in MDD, first of all, we take a step back and look at both of these indications. These are highly prevalent indications. There are over 50 million patients in the United States for both indications. And there's a still very significant unmet need. As we conduct market research with HCPs, we see that the unmet need is greater than 70% across both the indications. So even with the care that they have access to today, there's still something left significantly lacking in the treatment paradigm. So we know that payers do manage drugs and branded drugs that enter the market typically have a step or two. And so we believe that, that can narrow the overall addressable market slightly. But there are, for both GAD and MDD, a significant number of patients that are going to benefit if approved, from DT120.

Our next question coming from the line of Sumant Kulkarni with Canaccord.

As we eagerly await all the data you expect to announce this year. I have 2 questions, one on product development and the other on the commercial side. First, conceptually, we think investors are perhaps somewhat unfairly holding psychedelic therapeutics to a higher bar on point separations on scales in clinical trials. But our view for some time now has been that where the bar really should be different versus standard of care is on durability of effect. Is that a fair real-world characterization from your perspective? And I'm asking that because I don't think I heard an explicit callout for durability in your earlier answer on clinical relevance of a STAT6 on HAM-A and perhaps even more so on MADRS.

Yes. No, thanks so much for the question, Sumant. When we think about durability, there both the practical limitations of how long out in time you can look at single-dose durability in a placebo-controlled manner. There are certainly insights that we can gain beyond that. And in our conduct of the studies, we'll be looking the response patterns and the ultimate duration to events beyond just a 12-week period. But when we look at the landscape, 12 weeks is the outer bound of what most studies, particularly drugs that don't require a long time, for instance, SRIs can take many weeks to show any sort of activity. And so of course, sponsor in those studies would wait well beyond that to try to drive that separation. But when we think about the durability and our dialogue with regulators to date, the ability to show durability at 12 weeks past a single intervention is really at or close to the highest bar one could set for a drug. And so part of the decision-making in the design of our Phase III program was to have our primary endpoint be at that time, we would be showing if successful in these studies, really the longest durability of response that we could hope to or could hope to be established with -- in a parallel group phase of the study. And that stands out among all of the product candidates that we're seeing in late-stage development, certainly in our field. So we absolutely agree that durability is important and that durability well beyond a few weeks after a single treatment or the last treatment of drug is really meaningful and why we've designed our studies the way we have.

Got it. Yes, that's really why I was asking because you've shown really good durability so far. And on the commercial side, Matt, you mentioned a "high-touch white glove experience." So what are your latest thoughts on pricing in MDD and GAD, at least relative to SPRAVATO for TRD, if that's still a good benchmark? And what fraction of that high-touch white glove experience can be paid for by insurers?

Yes, thanks so much, Sumant. Yes, I'll just say briefly, I think -- and I'll turn it over to Matt. I think the -- when we think of pricing, it's really premature to talk specifically about pricing. But when we think about the dynamics, we continue to believe and sort of build conviction in our belief that the failure of currently available therapies to address a patient's depression or anything else is not a good proxy to define a population. And that what we see also in a lot of our HEOR work is that severity is a huge driver of disease burden. It shouldn't be surprising. The fact that drugs that don't work particularly well in a population haven't worked in the population doesn't mean that those who were underserved by those therapies are worse off necessarily. And so while we understand the dynamics of likely not being a first-line therapy for everyone, we do think that those distinctions are somewhat artificial and as a result, something that we both can look at within our subpopulation in our studies, but wouldn't sort of shy away from things like SPRAVATO as a comparator given the sort of artificiality of that distinction. But I'll turn it over to Matt to comment further on that.

Yes. So Sumant, as we think about the high-touch or white glove type of orientation we have for this launch is really to remove any friction that a patient or provider could experience. And so that will involve a hub service model, being really clear on the reimbursement pathway, how to bill and code, et cetera, ensuring that the patient out of pocket is not an obstacle, basically removing any of the obstacles to get to therapy as quickly as possible. That's our ambition. That's what we're building towards, whether it's through field team and high-touch field team exposure to either HCPs or otherwise in market access and ensuring that we have a seamless hub model that really helps coordinate all of the different touch points to ensure that the patient experience is positive.

And that's all the time we have for our question-and-answer session. I will now turn the call back over to Mr. Rob Barrow for any closing remarks.

I want to thank everyone again for joining us on the call today. We are incredibly excited to come to our top line readout for Emerge first in the months ahead. And with 3 pivotal readouts across the course of the year, we think this is really a defining year for us and are incredibly excited to get to those data readouts. So thank you again for joining us today, and I hope you'll join us at our upcoming events in April and thereafter.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.