Definium Therapeutics, Inc.

Good afternoon. I am Geeta Jain, Head of Investor Relations, and thank you for joining us today for DFINIUM 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 investor section of DFINIUM's website at DFINIUMTX.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 Carlin, our Chief Medical Officer, Brandy 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 runaway, 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 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 DFINIUM's normal course of business. Your caution not to place undue reliance on these forward-looking statements, which are made as of today, May 7th, 2026. DFINIUM 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, Geeta, 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 continue 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 three readouts anticipated across two of the largest indications in psychiatry, Decinium 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've established a constructive working relationship with FDA and will move as efficiently as possible towards an NDA submission subject to positive physical data. Beyond our ongoing phase three programs, we plan to expand development of DT120-ODT into additional indications, including post-traumatic stress disorder, or PTSD, with a 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. And I'll turn it over to Dan to go into more detail on our clinical program.

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 three 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 micrograms. 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 prosocial 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 three 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.

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 share 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 intervention. 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, Bithynium 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 Brandy 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 DFINIUM. As we entered 2026, we were pleased to have the financial flexibility to accelerate several key initiatives in parallel, including ongoing phase three 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 program. 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 mark-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 31, 2025 to $18.90 at March 31, 2026. Turning to the balance sheet, we ended Q1 2026 with $373.4 million in cash, cash equivalents, and investments. We believe our capital position provides sufficient runway to fund planned operations through multiple anticipated clinical read-ups and into 2028. 2026 is shaping up to be a data-rich and strategically important year for DFINIUM. 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, Brandy. 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 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 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.

Your line is now open.

Hi, 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 Matisse at CFAW. 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? And in these long-term data, would patients need to retreat a certain amount of time 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 and the time of filing and at various milestones between here and there, we would 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 treatment patterns that diverge across different patient populations or different patients to mean that six months of treatment can look like one dose or multiple doses. And so something we're really interested in characterizing, of course, in our phase three program. But 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've deposited phase three data. Dan, you want to 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. And the value of that is multiple, 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. So 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. So that's another advantage. And then 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. So 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. So 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 . Your line is now open.

Thanks. So 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. So that's number one, sort of a, I guess, REMS-related question on that front. And then 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 first placebo as opposed to including a low 50-microgram 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. So the situation in the clinical trials, of course, is that per FDA direction, we have a in-person lead monitor and then a secondary monitor who can watch remotely via video. And that's been the condition for the 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 that 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. But, you know, with the evidence that we're accumulating along the way, it adheres to the evidence that we've been able to establish for what constitutes safety and efficacy. And I can comment on PTSD as well, if you'd like, Rob.

Yeah, please, that sounds great.

Yeah, sure. So, across the phase three program, we have combined Stephen Stewart, MD, Studies right we've got studies with two arms and then in two cases we've added this lower enrolling. Stephen Stewart, MD, 50 microgram confounding right and that's not an analytical arm is an arm or we're interested in the performance of the 50 microgram drug. Stephen Stewart, MD, Rather, those arms have existed to confound the understanding of people in the other arms as to as to what they got so in each case for jd and mdd are. 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 any other psychedelic for that matter. So that's what we did in PTSD. We think head-to-head is the best way to establish evidence of efficacy. And 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 this end which we've guided starting imminently all of that will accumulate to help us understand what if any effect that 50 microgram 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 and also whether that has any effect on the measured outcomes. So 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. But 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. We'll move it for our next question. And our next question is on the line of Andrew Tsai of Jefferies. Your line is now open.

Hi, it's Brian Bolton here on for Andrew Tsai. Just two questions. First, on patient journey, you mentioned Phase III would be a five- to eight-hour patient journey that lasts up to 12 hours in Phase II. Can you talk a bit about what gets you closest to five-hour journey as opposed to eight? What do you need to establish with the FDM Centers to make it happen? And secondly, your response to Phase II, the GAS study, but actually going higher compared to other GAD studies. How are you thinking placebo might trend in the phase 3s? And then same goes for the phase 3 MDD study as well. Thank you.

Yeah, thanks so much, Brian. So, yeah, I think in terms of the first question and the criteria, some of the changes, and we highlighted this a few weeks ago at our event, both formulation where we use an oily dissolving tablet in our phase three program where we see faster absorption we think could translate into a better profile in terms of resolution of symptoms, but 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-microgram dose in Phase II, and therefore conservatively, and think appropriately conservatively, extended the monitoring period in Phase II up to 12 hours and had an 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 2 study, we made revisions both, of course, to the formulation, but also to that procedure, that checklist that we're using. And in Phase 3, we feel quite confident that we'll be moving in a shorter direction. That's what we're seeing so far. And so I think that combined with the reality that the change from a 12-hour monitoring period to an 8-hour monitoring period being required for all the participants in the study was driven by discussions with FDA and based on those data. So we feel quite confident that we're heading in the right direction there. And 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, So you rightly noted we had a remarkably high placebo response in the phase two study. If we just focus on the GAD symptoms or GAD AMA scores for a moment, what we saw there is, and this would be consistent across any modality and 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. And so 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 two that we now in phase three 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 two. And as we look to the phase three program, having a lower allocation ratio And having a reason for patients to stay in the study should both reduce at least two or perhaps even below historical averages for the placebo response. That would be true, we'd expect in both GAD and in NDD. 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 and daily drug studies. And it wouldn't be surprising if we saw a lower-than-average placebo response across the Phase III programs here. But given that we've exceeded such a high placebo by such a wide margin in Phase II, we feel quite confident no matter what that we'll be in a great position ending in the Phase III data.

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

Hi, good afternoon. This is Basma on for Mark. 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 going to be efficacious? And also, can you remind us of the study powering assumptions? The second question is, do you think for the submission in MDD or the GED, whatever comes next, that you can leverage the safety data from the GED, or you're going to have to collect another set of exposure data in the relevant patient population. That's it for us. Thank you.

Yeah, 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, but ICH guidelines aren't, for patient exposures, aren't disease or disorder specific. So they would expect a huge population requirement like you see from ICH1 or anything. Dan, I'll turn it over to you to the other one.

Yeah, so great question about PTSD and, you know, having done our dose range finding study in phase two and getting great confidence in our phase three 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. And 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 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. So we go into PTSD with the same confidence we went into MDD with the dose that we selected initially for patients with primary GAD. And 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 MADDRS 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 Francois Prespoys of LifeSide Capital. Your line is now open.

Thanks for taking the question. So 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 probability of success or whatnot of the trials, is there more confidence in one versus the other? And 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. And we've said this in a few different ways, and obviously we've introduced some new slides on the deck now to look at the GAD-MDD overlap. But as you noted, it really is, in the vast majority of patients, something of a temporal distinction. These are folks who 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. So they have start points and end points. Whereas GAD, we 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. And 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. And so 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. And 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 year or two years at the most, And often much more recently than that. So it's more like resetting a state that the person will will get back to and has been in more recently, whereas GAD is more of a change to a to a state that someone probably hasn't been in in quite some time because of the the longitudinal nature of the disease. So MDD has historically been an easier target, and that, in part, is what gives us great confidence. We also, of course, saw in phase two that we were able to move the madras 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 it, and we still saw quite a bit of movement. So 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 because 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, but also with the dropout rate and the data replacement strategy, taking that already actual high placebo response and making the measured placebo response actually over-represent the background real placebo response. So that's probably more causal than the disease state itself.

Maybe, thank you for that. And maybe if I could jump in quick with Matt. Matt, you made a comment there that you guys have shared before. But can you just help us understand, we don't hear this much, 1% penetration of the TAM equals to about 2 billion. So can you help us understand how that TAM, how do you handle the overlap of MDD and GAD to get to that number? And then 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. So, the 4.2 million patient number that I cite is, it includes any of those patients who have both. And so, 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. And so that's been in our plans, and that's an operating assumption to submit once we get it 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 Stravapoulos of Kantor. Your line is not 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 Madras score of 20 or greater. Could you help us understand why 20 was chosen? And 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. And there are a couple of, 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. But 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 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. And so 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 because, of course, in the end of the day, clinical judgment rules everything. And these scales, because of their intensiveness of administration, or not often used in clinical practice. So 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 that will very much push them in the direction of using therapies like ours.

I'll add one bit of color. there too, Sam, which is just that while there's a lot of discussion, of course, about the various subsets of MDD and 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. So finding patients who have severe symptoms and improving those down to a state where that functional deficit is improved meaningfully. And 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 siling ourselves into a small subset of the population that just didn't respond to two PSSRIs.

Very clear. Thank you. And if I can just sneak in one more question. So with interventional psychiatry being increasingly integrated into practices and healthcare systems, what preparations are underway at clinics to pivot and deliver DT120 operationally and 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. And 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... the anticipation and the receptivity of the market for these interventions as they make their way into market. And certainly there's a high anticipation for DT120 and some of the data that we shared just a couple weeks ago, I think really highlights the momentum and the receptivity of the market. So 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 from the line of Matthew Hershenhorn of Oppenheimer. Your line is now open.

Oh, 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? And 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. And, 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 the clinics have been thinking about this at least early on has been to allocate certain amount of space and then they will 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. So, you know, this is something that's really going to 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 downstream in years thereafter.

Got it. Thank you so much. And 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. And 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 want to take that one?

Yeah, happy to. There we go, off mute. So 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. And so particularly with folks with 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, 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. And we think that really is a differentiated advantage of the drug itself.

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

You know, what I didn't say was the second half there about the VA, and, you know, we've been working with VA researchers on our research to date, and of course, as we move into the world of PTSD, we will continue to deepen and strengthen those relationships. And, of course, we're continually seeking advice from experts across the different conditions we work with, but 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 Karkarni of Canaccord Genie, where 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? Would 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. Obviously, we're having a lot of discussions with FDA and have been around that appropriate strategy. I think what we, 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 and 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. I would say some of that's going to 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, and if there's an extraordinarily large effect that we're observing that would imply, you know, quite small studies needed to replicate that. So, something's going to be ultimately informed by the data and subsequent discussions with FDA, but we feel quite confident in the position for filing 120. And 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 get into the patient population if we're fortunate enough to get a drug approved.

Got it. Thanks. And 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, Amant. 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. And so our targeting model, our value proposition is really aimed at both indications. 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. And so 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. So we do believe that there's a lot of GAD out there that isn't adequately diagnosed in the ICD-10 data, but we believe that that will also change with therapeutic intervention that meets that need.

And 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. It's a good question. And 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 recently. like less than about four years ago. So we've been going at an incredible pace of development. And those are the things that we can, of course, control and put in all the time and effort and do research the right way to move the program forward to pivotal data, which we have coming up very soon. So what comes after that? And obviously with novel programs with FDA, there certainly can be advantages. There's also potential risks. I think one thing that's particularly important for our program, too, is this opportunity to potentially go after both of these indications. And 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 CMPB. So we've, of course, seen some positives come out of that. We've seen some risks associated with that. So we're going to keep with our great dialogue with FDA and continue to look for opportunities to accelerate anywhere we can. But right now, getting the data and going as efficiently from there towards an NDA application is where we're focused. Thank you.

Thank you. One moment for our next question. Our next question is from Chris Chen of Baird. Your line is not 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. And if you do go slightly over that eight-hour window, is it still possible to still secure a label with an eight-hour treatment window? Thanks.

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. And we'll do the same in terms of how we have been doing. analyzing the end of study checklist and when patients can be cleared for monitoring. And, 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. So, 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 Striccio of HCWinRANCO. Your line is now open.

Hi, it's Arabella. I'm for Patrick. Thank you so much for taking the question. I guess now that DEA rescheduling can be done after a successful phase three, how much time is that realistically actually going to save? And then I guess how are you thinking about initiating those conversations once you get the data? And then 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.

Yeah, thanks, Andrea and Bella. I think you're referring to the executive order that President Trump signed indicating the DEA should look at scheduling their scheduling assessment after phase three 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 90 days, which is the timeline right now if they get to an interim final rule and issuance of the schedule for the approved product. So there's a real opportunity, and it's something we've been actually quite engaged with for a while, exploring opportunities to not shortcut anything, but to streamline the 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. It was 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 with DEA. To your second question, I'll turn it over to Dan to briefly touch on 402.

Dan, thanks for asking about 402. We'd love to get a chance to talk about it. So as we've said before, we're doing a pretty interesting signal of efficacy study in ASD. And 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, and then late in the dosing experience, and then again as the drug wears off. And so to do that, we've constructed What might be a little bit skinnier instruments that 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. So 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. We'll move on to our next question. Our next question comes from the line of Ami Fadia of Needham Company.

The line is now open.

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 the treatment and the label, and also how much data do you think you need to have the conversations with payers around, you know, coverage and pricing. And then 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.

Yes, thanks so much, Ami. So, 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 out briefly that in precedent drug approvals, particularly with antidepressants, 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. And so we are pushing the bounds of what an acute study can do in this way. A single dose where we're following patients for 12 weeks and GADA primary endpoint at that 12 weeks, which is patients with GAD do not spontaneously have 12 weeks of significant improvement. So 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 patients intervals for retreatment and sort of overtime retreatment patterns, what happens upon subsequent retreatment, all the things we're trying to characterize there. But 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 remainder of this year and as we continue to progress towards a position of filings. In terms of capacity, 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, with any of the models. that are out there projected for adoption. So we do not see a sort of capacity constraint. One of the things we, for those of you who were in attendance in New York a few weeks ago with us, try to bring a little bit of clarity and demystify what it actually means to set up a treatment room. If you have a room and a site is willing to spend a few hundred dollars on making it a little bit more comfortable, that might be better for patients. But if you have a room where someone can be for an extended period of time, in a current treatment facility, that's enough. And so we do not see that there being a substantial financial or logistical bottleneck. People use the term infrastructure, but that's far too heavy handed of a word. So 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. And we think there'll be a great incentive and a great desire to adopt both treatment centers and 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.

All right. 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, and we'll look forward to sharing those data in due course. Thank you all.

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