Definium Therapeutics, Inc. (DFTX) Earnings Call Transcript & Summary

Hello, and welcome to the Definium Therapeutics Phase III Panorama top line results call. Today's call is being recorded. [Operator Instructions] I would now like to pass the call over to Rob Barrow, Chief Executive Officer. Please proceed.

Hello, everyone, and thank you for joining us this morning. I'm joined today by our Chief Medical Officer, Dr. Dan Karlin, Chief Financial Officer, Brandi Roberts; and our Chief Commercial Officer, Matt Wiley. We could not be more excited to be here with you this morning to share the top line results from Panorama, our third pivotal study of DT120 ODT 100 micrograms in our second Phase III study in generalizing anxiety disorder, or GAD. Before we get started, please note that on today's call, we'll be making certain forward-looking statements. We encourage you to review our SEC filings for a discussion of the risks and uncertainties associated with these statements, including the risks described in our most recent annual and quarterly reports. Today's results mark an important milestone for Definium in our DT120 program as we have now replicated the unprecedented results reported last month from Voyage, our first pivotal study of DT120 in GAD. Having delivered 3 positive Phase III studies across GAD and MDD over the past 12 weeks, our confidence in the transformational potential of DT120 has never been higher. We believe DT120 represents a highly differentiated profile with the potential to redefine standards of care and become a best-in-class therapy across 2 of the largest and most impactful indications in psychiatry. I'd like to thank our study participants, investigators, partners and the incredible Definium team for making all of this possible. We are deeply appreciative and humbled by the commitment, trust and belief in our shared vision. Only together could we have arrived at this remarkable moment. At Definium, we have an ambitious vision and believe profound change in psychiatry is truly possible. We set a high standard for DT120 to demonstrate that a single supervised dose can deliver rapid, robust and durable efficacy and offer new hope to the tens of millions of people living in anxiety, depression and other mental health disorders the burden that GAD places on patients, families and society is enormous, impairing daily function, productivity and quality of life, and that burden continues to grow. The prevalence has more than tripled since the early 2000s, and GAD is now estimated to be experienced by 10% of the U.S. adult population. Promisingly, we've entered a new era of far greater awareness and openness around anxiety and its impact on people's lives. Despite this need and awareness, there hasn't been a new drug approved for GAD since 2007, and that's not because of a lack of effort. Over that period, roughly a dozen drug candidates spanning numerous mechanisms have advanced into late-stage development. Nearly all have failed, none have been approved and most have been unable to demonstrate meaningful improvement over placebo. That long period without success is also have to field without a modern benchmark for what truly compelling efficacy in GAD looks like. We believe the Panorama results we're sharing today continue to change that picture. They represent the promise of real progress for patients with GAD and further reinforce the potential of DT120 to help usher in a new era of psychiatric care. Panorama marks our third pivotal readout for DT120 this year and our second pivotal readout in GAD. As with our Merge and Voyage readouts, Panorama met its primary in all key secondary endpoints with a high degree of statistical significance. Consistent positive outcomes across 3 complementary studies further strengthens our confidence in DT120's potential and the broader opportunity ahead. In Panorama, DT120 ODT 100 microgram showed a 5.1 point placebo-adjusted improvement over placebo at the week 12 primary endpoint with a p-value of less than 0.0001. This efficacy was rapid with a 5.3 point placebo-adjusted improvement on the HAM-A at week 1 and a 0.8 point placebo-adjusted improvement on the CGI-S at day 2 and both with p values also less than 0.0001. DT120 was well tolerated with no new safety signals identified including no suicidality signal. We continue to observe efficient and predictable treatment session dynamics with an average time to clearance on the structured end of session checklist of 6.2 hours and 94% of participants clearing by hour 8. Panorama included the DT120 ODT 50 microgram arm, which served as a functional control but was not powered for or assessed and prespecified statistical comparisons. The 50-microgram dose produced a 3.6 point improvement over placebo at weeks 4 and 12, approximately 50% and 29% less than the 100-microgram dose. The results from both Voyage and Panorama are closely aligned with the dose response model generated from our Phase IIb study. It's also worth noting that as in Phase II, at both the 50- and 100-microgram doses of DT120, over 90% of participants correctly guessed their assignment of drug, supporting the conclusion that the dose response observed is a real treatment effect and is not attributable to functional unblinding. To further emphasize this point, across studies, the 100-microgram dose has consistently exceeded our efficacy target of a placebo-adjusted improvement of at least 4 points on the HAM-A. The 50-microgram dose has not. At the same time, the adverse event profile was similar across the 50-and 100-microgram doses and the median time to end of session clearance was 6 hours for both. In our view, these results decisively settle the question of dose selection and clearly support the advancement of DT120 ODT 100 micrograms. To put these results in perspective, we have now consistently shown that DT120 100 micrograms delivers a large effect that stands out against the current standard of care in GAD at both week 12 and at earlier time points. In summary, in a disorder with high prevalence, high burden, high unmet need and no innovation in decades, a single dose of DT120 has consistently shown a rapid and durable effect with a magnitude that is considerably larger than the drugs approved today. We cannot be more excited about what this can mean for patients and the potential to redefine what they can expect from psychiatric care. With that, I'll turn the call over to Dan to walk through the results in greater detail.

Thanks, Rob. Today is another important milestone for DT120 and for patients living with GAD. As a psychiatrist, I have seen firsthand the profound impact that chronic anxiety can have on every aspect of a person's life. While existing treatments can help some patients, many continue to struggle with persistent symptoms or wait weeks or months to experience meaningful relief. The positive Voyage results we reported in August marked a major step forward. And today, Panorama provides further confirmation of DT120's potential in GAD. Consistent findings across 2 Phase III trials are especially meaningful because they reinforce the reproducibility of the efficacy signal and the strength of the overall clinical profile. Let me begin with the study design. Panorama is comprised of 2 parts: Part A, a 12-week randomized double-blind period; and Part B, a 40-week extension period with opportunities for open-label treatment. As in our prior studies, participants were tapered off background antidepressant and anxiolytic medications prior to enrollment. Notably, as with our entire development program, we did not provide any psychotherapeutic intervention as a part of the study. In Part A, 245 participants were randomized in a 2:1:2 ratio to receive a single dose of DT120 ODT 100 micrograms, DT120 ODT 50 micrograms as a control or placebo. The primary endpoint was the change from baseline and HAM-A total score at week 12 assessed by independent central raters blinded to treatment assignment and visit number. In Part B, participants continue to be followed for an additional 40 weeks and complete regular efficacy assessments. Participants who meet the prespecified treatment threshold of HAM-A score of 16 or greater, become eligible to receive an open-label dose of DT120 for up to 4 open-label treatments over the course of the study. The treatment threshold of the HAM-A score of 16 corresponds to the cutoff for moderate illness and reflects an increase in symptom burden such that participants are experiencing functional impairments. As in Voyage, we selected this threshold prospectively as a clinically meaningful marker for when additional treatment may be warranted. We randomized 245 participants, 96 to DT120 ODT 100 micrograms, 52 to the DT120 ODT 50 microgram control and 97 to placebo. All randomized participants were included in the intention to treat population. Approximately 90% of participants completed Part A. Participants entered the study with high disease severity as reflected by baseline HAM-A and CGI-S scores of 28 and 4.7 across treatment groups. These values place participants firmly within the severe range of anxiety. Demographics and baseline disease characteristics were generally balanced across treatment groups. We observed prior psychodelic use consistent with what might be expected in a broad GAD population with 14% of participants of reporting any previous psychedelic use and only 7% reporting prior LSD use. Importantly, these characteristics were balanced to [indiscernible] treatment arm supporting the comparability of the study groups at baseline. Despite a limited number of available treatment options, this population had substantial prior treatment experience and a high disease burden. Half of participants reported receiving 2 or more prior treatments for GAD and 3/4 of participants had severe anxiety at baseline. On average, participants have been diagnosed with GAD for approximately 9 years and reported experiencing anxiety symptoms for nearly 18 years prior to enrollment. On the HAM-A, which was the study's primary outcome measure, DT120 100 micrograms demonstrated rapid, robust and durable efficacy. At every measured time point, DT120 100 micrograms statistically and clinically exceeded placebo on the HAM-A with a p-value of less than 0.0001. At week 4, participants receiving DT120 100 micrograms demonstrated a mean improvement of 12.3 points from baseline, corresponding to a placebo-adjusted difference of 7 points. At week 12, the primary endpoint, DT120 achieved a mean improvement of 9.8 points in a placebo-adjusted difference of 5.1 points. Rapid relief is particularly important for patients in distress. By week 1, the first efficacy assessment following treatment, participants receiving DT120 100 micrograms showed a mean improvement of 9.8 points from baseline, corresponding to a placebo-adjusted difference of 5.3 points. Taken together, these results demonstrate a treatment profile characterized by rapid onset, robust magnitude of improvement and durable efficacy through the primary endpoint after a single administration of DT120 100 micrograms. A secondary measure of disease severity is the CGI-S, and here, we see that CGI-S tells essentially the same story as the HAM-A. Key secondary endpoints shown here are change from baseline in CGI-S score at week 12 and early improvement measured at day 2. Notably, these instruments use different mechanisms to assess the underlying illness and are conducted by different readers. HAM-A is assessed by independent centralized raters, while CGI-S is a local site-based clinician-rated measure. The consistency across these independent measures gives us tremendous confidence that the treatment effect represents real, meaningful clinical improvement in study participants. Categorical outcomes provide another way to understand the clinical relevance of the effect. At week 12, 32% of participants receiving DT120 100 micrograms met the response criteria of at least 50% HAM-A improvement compared with 14% on placebo. 35% achieved mild or better status compared with 17% of placebo. Remission was achieved by 15% on DT120 100 micrograms and 4% on placebo. Across each threshold, more DT120-treated participants achieved a clinically meaningful outcome after a single administration. The week 12 HAM-A treatment effect was maintained across each subgroup we analyzed. Importantly, the effect was maintained in participants would receive 2 or more prior GAD medications, a population with substantial unmet need and fewer remaining treatment options. The consistency of the results across these subgroups strengthens our confidence that the benefit observed in Panorama are broadly applicable across the GAD population and are not being driven by any single patient group. Turning to safety. The adverse event profile was consistent with our prior DT120 experience. Adverse events were largely mild to moderate in severity and most treatment-emergent adverse events occurred and resolved on dosing day. There were no study drug-related serious adverse events, no suicidal or self-injurious behavior and no indication of increased drug-related suicide risk. Overall, these findings continue to support a favorable and predictable tolerability profile. Treatment emergent adverse events were reported in 95% of participants receiving 100 micrograms, 96% receiving 50 micrograms and 63% receiving placebo. Two treatment emergent serious adverse events occurred in the 100-microgram arm, 1 in the 50-microgram arm and 1 in the placebo arm. None of these was study drug related. No treatment-emergent adverse events led to discontinuation or death. Adverse events were collected under FDA guidance for psychodelic drug development, which includes expected effects characterized as positive, favorable or neutral. Among treatment-emergent adverse events occurring in at least 10% of participants, the most frequently reported events were the expected transient, perceptual, affective, cognitive and behavioral effects associated with DT120 administration. These events occurred primarily on dosing day were generally mild to moderate in severity and resolved during the supervised treatment session. Rob mentioned this earlier, and we believe treatment session dynamics remain one of the most important aspects of DT120's overall profile. The DT120 session is well matched to the needs of GAD patients with a combination of session duration and depth of experience that continues to produce efficacy outcomes like the ones we've shared with you today. We use a structured end-of-session checklist to assess readiness to leave the treatment setting safely. The average time to clear the checklist was 6.2 hours with more than half of participants clearing at our 6 and 92% clearing by hour 8. Across all known Phase III DT120 dosing sessions, we see a remarkably predictable duration with the vast majority lasting between 5 and 8 hours. We believe this translates cleanly into clinical practice where the end-of-session checklist can be easily implemented to inform medical decision-making by the clinical staff supervising sessions. Now we turn to Part B, the 40-week extension phase. As a reminder, participants are eligible to receive up to 4 open-label treatments with DT120 for moderate or worse disease severity, as assessed by the centrally rated HAM-A. This phase aims to better understand long-term durability from Part A, subsequent treatment patterns, response to retreatment and durability over the full year of observation and dosing opportunities. At the time of this analysis, 86 participants originally assigned to DT120 100 micrograms, 42 assigned to the 50-microgram control and 76 assigned to placebo had entered Part B. Today's discussion focuses on data through week 28, where enough participants have been evaluated to provide a meaningful analysis. The demographics and baseline characteristics of participants entering Part B were generally consistent with the broader Part A population. As anticipated, multiple treatment trajectories emerge with the participants receiving intermittent open-label treatment based on symptom recurrence and retreatment eligibility. The data showed a distribution of participants receiving 0 to 3 open-label treatments through week 28. These early patterns provide an encouraging first look at how DT120 may be used in a real-world treatment setting. Longitudinal HAM-A results showed durability from the initial active dose and additional improvement after open-label treatment. Their convergence towards the original active group provides early supportive evidence that subsequent administration can produce additional benefit. Notably, about 1/4 of patients in the active arm remain mild or better for roughly 6 months without needing any additional dose. As with Part A, we can look at response and remission over time in Part B. Across each of these measures, patients continue to benefit with subsequent treatment administrations. Response and remission rates improved through week 28, demonstrating sustained disease control. The consistency of these findings across multiple clinically meaningful endpoints gives us strong confidence in DT120's potential to safely deliver durable efficacy with intermittent symptom triggered retreatment. And with that, I'll turn the call back over to Rob.

Thanks, Dan. As I said at the outset, our goal at Definium is to enable a new treatment paradigm that can fundamentally reshape clinical practice in psychiatry. We believe the landmark results shared today represent another important step toward that goal. Across 4 studies with various designs, populations and indications, DT120 has demonstrated a large durable effect. While the complementary study designs have yielded differences in symptom presentation and the variance of study outcomes, the magnitude of effect and high degree of statistical significance has remained remarkably consistent. We are nearing completion of our registration and development program for DT120, which has always been grounded in precise science. This includes 4 positive Phase II and III studies with complementary designs, a comprehensive clinical pharmacology, nonclinical and CMC program, all of which have benefited from close regulatory engagement under the Breakthrough Therapy designation program. We've also gone to great lengths to address the key considerations for the development of psychedelics and believe the consistent efficacy and safety data generated to date support a compelling argument for the safety and effectiveness of DT120 ODT 100 micrograms. We're excited to hold our pre-NDA meeting in the fourth quarter, and we anticipate NDA filing for DT120 in the first half of 2027. I believe there is a significant opportunity to bring into a differentiated treatment to the patients who continue to need better solutions. Today, an estimated 50 million adults in the U.S. are affected by GAD or MDD, with approximately 26 million diagnosed, 13 million receiving pharmacotherapy and more than $4 million having been failed by 2 or more treatments. We view this initial scale as the starting point rather than the ceiling with a long-term opportunity that can meaningfully expand as we continue to generate evidence, broaden access and reach additional patients across these large and underserved markets. With such a major need, even modest uptake has the potential to deliver impact for a sizable portion of the population. The large and growing ecosystem of interventional psychiatric clinics provides a springboard for exactly this sort of adoption. With around 8,000 such sites today, if only half of them were to treat 2 patients per month, this could represent over 100,000 patients in a year. Based on our market research, this is well within the excess capacity that exists today, and we continue to see a high degree of enthusiasm for adoption among these providers. We're making great progress in preparing for commercial execution and the launch of DT120. We continue to solidify our commercial team with the addition of key leadership over the course of 2026, bringing immense experience and importantly, a shared philosophy that has driven our success to date. Part of this philosophy is a commitment to delivering the best patient and provider experience possible. We are highly focused and heavily invested in optimizing patient support, provider enablement and site readiness to help remove barriers and create a seamless treatment experience for all those involved in the process. We continue to make progress on 2 distinct value drivers, our continued commitment to excellence in clinical and regulatory execution and setting the standard for commercial impact and execution to bring this clinical promise to the patients as impactfully as possible. We're working tirelessly to build Definium into a psychiatry powerhouse that can reset expectations for what patients and providers can expect from care. Today's positive Panorama results further strengthened the DT120 story and build on the positive Phase III results from Emerge and Voyage, which our team delivered in the past 12 weeks. With approximately $1.1 billion in cash and investments, we are well positioned to advance toward our planned NDA filing, prepare for commercialization and continue investing in our broader pipeline. We believe the opportunity ahead is significant, and we look forward to delivering on the many milestones still to come. Before we go to Q&A, I want to say a special thanks again to our incredible team at Definium. We've built an organization of exceptional people who are deeply passionate about our mission and the patients we serve. To deliver consistent landmark results in such a rapid succession is truly extraordinary and a testament to the amazing people we have at Definium. With that, we'll open up the call for Q&A. Thank you.

[Operator Instructions] Our first question comes from Paul Mattias from Stifel.

Can you guys hear me?

We can.

Okay. Great. Awesome. Congratulations on the data. I wanted to just ask maybe a 2-part regulatory question here. So one, going into this pre-NDA meeting, what are the key questions, and what's your level of confidence that you have enough data to also file for MDD? And then second, can you remind us your agreement with the FDA as it relates to how much redosing data you need? And is it about like a certain number of patients getting a certain number of doses, or is this not as kind of quantitatively defined?

Yes. Thanks so much for the questions, Paul. Taking each of those one by one. I mean, our overall confidence going into the NDA meeting is extraordinarily high. We've had a very constructive relationship with FDA and continue to have a continuous dialogue there. And of course, with the data we've been able to generate, we think they're unequivocal and really answer the questions that need answering. In terms of alignment on MDD filing, this is exactly the purpose of our pre-NDA meeting is to talk about the filing strategy for GAD and for MDD. Of course, with the recent Breakthrough Therapy designation that we received for MDD, we're very excited about the promise that program holds and the high degree of alignment to efficiently bring that product forward. So we'll be eager to get to that pre-NDA meeting and come out of that hopefully, with clarity, we can offer to everyone about the filing strategy across both the indications. In terms of your second part of your question in redosing, obviously, we all have historically lived under the framework of ICHE1 and the requirement to dose patients at 1,500 independent patients, that's for chronic daily treatments though. And in this case, both the lexicon and the realities of how DT120 and other drugs in the category are being used are not at all like a daily drug. We're talking about a few intermittent administrations over the course of a year. And given the long history and the high degree of characterization we have for this program, and just in the Phase III studies alone, the over 1,000 treatment sessions that we've now delivered and have data for, we feel quite confident about where we are positioned today and the day we have available to us, which is why we comfortable that we'll be in a position to go forward with the filing in the first half of next year.

Our next question comes from Andrew Tsai with Jefferies.

Congratulations on another hugely successful readout. So in the -- I guess, the eventual label for GAD and MDD, I'd be curious how you would envision the front page label claim to read because we noticed that the FDA and EGM paper suggests how the FDA is permitting dosing intervals to be established in post-marketing setting. So it feels like the front page label claim could be quite broad for you guys. So I'd be curious what your thinking is, what you plan to propose to the FDA at the end of the day?

Thanks so much, Andrew. In terms of our development program, our intent has always been to have a front page label that indicates that these -- that the DT120 is indicated for the treatment of generalized anxiety disorder and for the treatment of major depressive disorder. Of course, there are other sections of the label where the dose and regimen and administration are described thoroughly, and certainly, over time, the historical standard, even for daily antidepressants, has been 2 acute studies and post-marketing studies then that establish maintenance regimen. Those maintenance regimen studies are often complex and for many drugs that are already approved have not succeeded even. So we haven't ever seen that be a barrier in a commercial setting to adoption. But based on our dialogue and based on our understanding and the data we've been able to generate today, we're going to be pursuing a broad GAD and MDD label that isn't restricted in terms of the exact interval or redosing dynamics because that aligns with what we've been able to demonstrate in the development program.

Our next question comes from Gavin Clark-Gartner with Evercore ISI.

This is Yash on for Gavin. Just a quick 1 from us. In theory, could the FDA potentially ask you to file the 50 mg in addition to the 100 given what the dose response curve showed?

Yes. Thanks so much for the question, Yesha. We certainly feel that any questions about 50 micrograms or functional unblinding have been settled by our development program. We have gone to the greatest length of anyone in the field to thoroughly interrogate this and now establish in 2 studies that in order to derive the kind of efficacy that we are targeting here, the 100-microgram dose is necessary. We would not feel comfortable with pursuing a 50-microgram dose and do not believe that the benefit risk assessment of these 2 doses would, in any way, support moving forward that dose. So while we're going to be having those discussions, of course, with pre-NDA and thereafter, we feel quite clear. And obviously, the data stand up behind that to decisively land on the 100-microgram dose and to really close the chapter on questions about 50 micrograms or functional binding or things of this nature.

Our next question comes from Marc Goodman with Leerink.

just to come back to this new FDA guidance, any general thoughts on anything there? Was there anything surprisingly, but hou can specifically focused on just commercialization and standardization and the monitoring of the dosing and just the end-of-session check risk, and how do you think that's going to play into what their commentary is there? And is there going to be a -- you've got 94% at 8 hours. So do you think the FDA says, well, are we at 100% at 9 hours? So this is a 9-hour session, and you think they're just going to leave it open to interpretation by each plant. I'm just curious how much you think there's standardization there?

Yes. I mean it's a really good question and obviously, some place that we've been extremely focused and I think a reasonable place for all of us to focus. As you correctly identified, we had a 94% ready at our rate rate, which I may have misspoken previously. But the ultimate -- what we're trying to enable here? We're collecting all of these data on end-of-session checklist. We're trying to standardize in the trials. We we examine in a very structured way what actually happens in the treatment room, what treatment session support really consists of? All of that is in service and being able to go to the agency with evidence-based arguments for what the minimum conditions for safety and efficacy are. We've noted throughout this program that by stripping away psychotherapy conducting the trial, by reducing the role of the treatment session support folks in the room, all of that's in service of establishing these minimum conditions for safety and efficacy because at the end of the day, clinical experience and clinical expertise ought to guide the delivery of this treatment in ways that exceed that minimum standard. So our best bet here is to go to the agency, show the curve, show when people are ready. I think there's a pretty strong argument to say that keeping 95% of people in who could be ready to leave because 5% might not be isn't absolutely the best move. So at the end of the day, it's a balance between safety and access and deference to clinical expertise and community standards that will emerge as we gain experience with this drug in the real world, if approved. One thing that we highlighted here was that we've now had more than 1,000 sessions with DT120 ODT 100 micrograms. And of those, 97% are ready to leave by hour 8. I think that's a pretty strong argument for a shorter absolute minimum time so long as there are standards for what constitutes readiness and that's what we've established with the checklist now.

Our next question comes from David Amsellem with Piper Sandler.

Maybe a question on commercial dynamics. We know GAD is a pretty expansive indication. But I guess, in practice, how do you think step-throughs in prior treatments on average are going to shake out before patients can get access to 120? Do you think ultimately this is going to profile as more of the, lack lack of a better term, treatment resistant population who've been through multiple reuptake inhibitors and even chronic exposure to benzodiazepine? Just wanted to get a flavor for how you're thinking about that in practice. I realize that, that also is leaned into a discussion on payer dynamics, but I would love to get your thoughts.

Yes. I'll go ahead and turn that over to Dan initially and certainly can have MATT into.

Yes. I mean I have a 2-part answer, I think, to this one, which is that, yes, at launch, we fully expect that we will be a step 3 therapy. That's been the case for every new antidepressant and anxiolytic for quite some time. That hasn't been a substantial barrier to success, however. By the time a GAD or an MDD patient reaches psychiatry and the sorts of providers who are likely to be our prescribers and provide our treatment session support, they, in many cases, have already had an opportunity to try and been failed by multiple SRIs. I think abenzodazabine requirement is pretty unlikely given the emerging evidence over the past decade about the effects of benzazepines. So yes, Step 3 therapy, but don't really see that as a substantial obstacle given where patients will be in their treatment journey by the time they reach the opportunity we have prescribed. There's another argument that I'll make very briefly here that certainly we'll hit on more over time, which is that in the prior treatment landscape, where subsequent drugs, where the new branded drugs were effectively the same as the prior drugs, Step 3 seems not unreasonable, right, a drug that has about the same efficacy, about the same mechanism but cost a lot more, well, okay, that makes sense to make folks try something that's very similar, but much less expensive. What we see with the data we've been able to present over these past 10 weeks with 3 positive Phase III readouts is a drug that works completely differently. DT120 offers a really different profile for how it can help people's disorder and their experience and their life change. And so what starts to come out of that is an argument for the STEP system that previously existed, not necessarily making sense, not making people wait and suffer when something that is more likely to help them more conclusively is waiting out there for them. So while we'll launch into a Step 3 environment, we think that ultimately, there's an argument waiting to be made for some change in the way that the dynamics of treatment courses work.

This is Matt. Just to dovetail on Dan's comments, we've spent a lot of time talking to payers over the years and everything that Dan said is consistent with what they've told us. The management of DT120, maybe similar to that of esketamine. Prior authorization with a 2x drug failure rate is likely. And that's our plan and operating assumption going to market.

Our next question comes from Brian Abrahams of RBC Capital Markets.

Maybe just a follow-up on the payer side. Just wondering if you could characterize kind of your latest payer discussions just in light of the consistency of efficacy that you're seeing that were robust effects, particularly in these more refractory patients? Any kind of changes or evolution in your view on the potential pricing power here? And congrats again on the data.

Yes. Thanks so much, Brian. I'll comment briefly and turn it over to Matt. We certainly -- we continue to sort of use a benchmark that's out there in the world today, and we're not in a position today, certainly to announced pricing until much later when a drug like DT120, which typically happens after approval interim final rule is issued. But absolutely, what you said is correct, which is that we see quite stark efficacy, something that really hasn't been seen before. And in this indication, it has been seen in a very long time. And so that certainly gives us a lot of negotiating power and positioning when you think about price, but I'll turn it over to Matt to talk a little bit more in detail.

Again, we've spent quite some time with payers and -- both in research and in advisory roles, and they've been impressed with the data to date. Obviously, with the data over the summer and the data presented today, I think that strengthens our argument with them. And the broad indication set that we're pursuing is also a great interest. So there's there may be additional value there as we think about the price point, but there's a lot of work to do between now and launch.

Our next question comes from Ben Burnett with Wells Fargo.

I will add congrats. I wanted to ask just 1 point of clarification real quick. And that's just on the CGI data, which I believe is Slide 17. It just looks like the table is showing a drug effect of minus 1.1, but the chart or the plot looks more like a minus 1.0. Just curious maybe 1 of those is a model estimate. But then my question is just around the discontinuations. So great to see no discontinuations due to adverse events. By our estimate, it looks like that maybe sort of 5 patients or so dropped off in each arm by week 12. Just curious if you had any color on the dropouts.

Yes. Thanks so much, Ben. I'll turn that over to Dan to talk about the dropouts.

Yes. So no single predominant reason for dropouts. We always see sort of a smattering of different reasons and sometimes it's just protocol noncompliance or lost to follow up. One interesting phenomenon though that we've seen in these studies that I have not really seen before is people leaving because they're doing extraordinarily well. And in any other drug study where you're giving some one daily drug, your folks who sustain the greatest efficacy from getting that daily study drug are unlikely to leave because they only get the drug by staying in the study. Whereas with our study, where we have this 12-week randomized double-blind period, with a single treatment session at the beginning, there are certainly people who have a tremendous response right out of the gate there and as a result, don't really see a reason to continue to participate in a GAD or MDD study. So that dynamic is a little bit different. And of course, when someone does extraordinarily well, the modeling that we do to fill in for missing data is going to modulate that, to some extent, and bring them a bit back toward the medium performance. But beyond that, nothing stands out as being unusual or different from what we would ordinarily see just in the course of a fairly long clinical study.

Our next question comes from Francois Briseboisfrom LifeSci Capital.

Congrats on the data. I was just wondering, in terms of the breakdown, if you talked about clinics, I think about 4,000, I believe that was by taking about half of them. I was just wondering if there's any more work done in terms of how the distribution is amongst the clinics? Is it -- would it be 2 patients a month or something? Or are there clinics where there's just so much more volume? And if so, what is the reason that you would expect some clinics to have way more volume than other clinics?

Yes. Thanks so much, Frank. There absolutely is a distribution that is -- if we look out in the world today, at least in terms of things like esketamine that are delivered, there's a high degree of concentration in a number of centers. And in that context, there's certainly a dynamic that could be a play that's driving certain centers to adopt a much higher volume framing and business for -- and it kind of makes sense for a drug that you have to administer up to 56 times a year. Doing it a lot and getting a pattern of retreatment for that drug, in particular, that requires rapid return by patients and rapid turnover. In this instance, we obviously don't know yet what the real world distribution is exactly going to look like, but we feel that there's some really great opportunity here for those sites that maybe don't set themselves up to deliver esketamine or ketamine on a recurrent basis and make that the entirety of their business, but want to offer more treatment options to their patients perhaps on a regular basis, but not every single day. So we certainly expect there will be higher concentrations of prescribers, that there will be a -- some centers that treat a lot more patients than others. But the dynamics here, really, what we've been after and what we're seeing is that it opens up a possibility for an even broader set of sites of care and providers that they could be involved in e eventual delivery of 120. And that's what gets us excited because that footprint out in the world today is quite large. And our point is that even modest adoption and a modest treatment rate really leads to some incredible opportunities to help many, many patients and for us is a uge opportunity for value generation. So our focus is going to be going as broad and as impactfully possible as we get out into that setting.

Great. And then if I could just lastly here. In terms of the -- I know that 50 and 100 weren't like power to be compared to each other. But I was just wondering what you make of the AEs being similar between the 50 and the 100? And also at the time, I think it was 6 hours to leave the clinic, I'm just wondering if -- what we should make of that? And also in the real world, do we expect the time, once people feel more comfortable, could actually come down for people to be ready to leave the clinic?