AtaiBeckley Inc. (ATAI) Earnings Call Transcript & Summary

All right. Good morning, everyone, and thank you for joining us for AtaiBeckley's 2026 Investor Day. Before we begin, I'd like to remind everyone that this call and presentation will contain forward-looking statements. These statements are subject to risks and uncertainties, and actual results may differ materially. We undertake no obligation to update our forward-looking statements, except as required by law. Additional information can be found in our SEC filings. With that, let's review the agenda. We're really excited to walk you through our strategy, clinical progress and our vision for leading a new era in interventional psychiatry. Today's presentations will focus on how our lead asset, BPL-003, is positioned to deliver rapid-acting, durable and scalable treatment options for patients with treatment-resistant depression and beyond. After a short break, we'll then turn our focus to a roundtable discussion featuring leading experts in the field followed by a moderated Q&A with our management team and the key opinion leaders. We have a full morning plan and I'm pleased to introduce Srini Rao, Co-Founder and CEO of AtaiBeckley, who will start the morning with an overview of AtaiBeckley's strategy and portfolio. Srini, over to you.

Great. Thank you, Jason, and thank you to every one of the audience who's made time to join us today on our Investor Day webcast. At AtaiBeckley, our mission is clear: to transform mental health care by developing next-generation psychedelic-based neuroplastogens that combine rapid onset, durable benefit and real-world scalability. We're uniquely positioned to lead this category with an approach built on four core pillars. Number one, we focus on indications with high unmet medical need like treatment-resistant depression, or TRD, and social anxiety disorder, or SAD. Number two, we're advancing therapies designed for rapid acting and durable clinical impact with the goal of moving beyond daily or frequent intermittent dosing paradigms. Number three, we've designed our products from the outset for real-world scalability. This involves using practical and familiar routes of administration and plugging into established care delivery models. And finally, number four, we are diligent in protecting our innovations with a comprehensive IP portfolio across compounds, formulations and methods of use. Together, these pillars define how we build, prioritize and deliver therapies that can truly shift the standard of care and transform patient outcomes in the mental health space. Now on the next slide, you can see our pipeline which spans across the TRD and SAD clinical stage programs and also includes our emerging discovery stage assets. We will, of course, focus on BPL-003's recent progress and advancement in the Phase III pivotal studies for the remainder of this call. Now let's take this opportunity to briefly touch on our other clinical programs, starting with VLS-01. This is a differentiated buccal film formulation of N,N-dimethyltryptamine or DMT that is being developed for TRD. In a Phase I clinical trial, VLS-01 demonstrated a promising profile that combines a short duration of subjective effects with encouraging tolerability. We are eagerly awaiting the top line data from the ongoing Elumina Phase IIb trial in the second half of this year. I also want to talk briefly about EMP-01 and highlight the positive top line results we announced last week from an exploratory Phase IIa trial in SAD. What really sets EMP-01 apart from racemic MDMA is its unique pharmacology. By eliminating the S-enantiomer of racemic MDMA, we reduced the stimulant activity and strengthened serotonergic effects. As we mentioned last week, the Exploratory Phase IIa study, the first of its kind in general SAD with a psychedelic compound, met its primary endpoint on safety and tolerability and moreover demonstrated very encouraging early signals of efficacy. The consistent gains across secondary and exploratory endpoints combined with a differentiated subjective profile, provide meaningful validation of both our -- of the compound and our development approach. Taken together, we are very proud of our leading portfolio of three high potential clinical assets and conditions with large unmet medical needs. So let's go on to the next slide. Depression and anxiety represents some of the most prevalent and burdensome mental health conditions globally. In the U.S. alone, more than 20 million adults experience major depressive disorder each year, and over 30 million experience social anxiety disorder across their lifetime. These are massive patient populations, but more importantly, they are populations where treatment innovation has lagged. The opportunity is significant, and as we'll discuss, we believe our clinical and commercial strategies are aligned to capture it. On the next slide, we expand on the unmet needs that continue to define the mental health landscape. Despite decades of available treatments, the reality is that many patients are still left without symptom relief for their mental health conditions. On top of that, most current therapies often take weeks to work if they work at all. Many require chronic daily or intermittent dosing that is often associated with undesirable side effects that many patients simply can't sustain. The burden is real and it manifests both chronically and economically. What's becoming increasingly clear is that next-generation therapies must do more than merely suppress symptoms. They need to meaningfully reset the underlying circuits to drive these conditions to thus provide long-lasting benefit. That's exactly the gap that psychedelic-based neuroplastogens aims to fill. The figure on the next slide lays out the mechanistic foundations behind our approach. Psychedelic-based neuroplastogens activate pathways that promote synaptic regeneration in neurogenesis, but they also disrupt maladaptive brain network activity. You can think of it as helping the brain escape entrenched patterns that often underlie treatment-resistant mood disorders. The acute biological effects are associated, of course, with a unique subjective experience. Beyond psychedelic phenomena, this experience may involve emotional release, perceptual shifts and cognitive reframing. Together, this combination of mechanistic neuroplasticity and the associated subjective experiences, are thought to underlie the rapid benefit seen with these compounds. This dual mechanism also seems to open a longer period of behavioral plasticity that in turn drives durable efficacy. This durability is critical to making intermittent dosing feasible. The shift to intermittent dosing promises to fuel the next phase of change and growth in the field of interventional psychiatry. The next slide outlines the progression of interventional psychiatry from devices like rTMS to pharmacotherapy starting with ketamine and then on to esketamine. These compounds represented a paradigm shift for the space when they were first introduced as they were the first drugs to offer rapid symptom relief. However, they lack durability and thus require frequent redosing. First-generation psychedelic products based on psilocybin or LSD offer both rapid onset and durability. However, both require many hours in the clinic. This markedly increases complexity, limit scalability and increases the burden on patients. This leads us to second-generation psychedelic-based products, the space where AtaiBeckley leads. Both BPL-003 and VLS-01 were purposefully designed for short, scalable in-clinic sessions. We've essentially taken the lessons from earlier interventional approaches, including SPRAVATO and design treatments that retain or possibly even improve upon efficacy while dramatically reducing complexity. This shift is foundational as it allows clinics to deliver high-impact treatments without sacrificing capacity and it makes these therapies accessible to many more patients. The next slide highlights this core pillar of our commercial differentiation strategy. J&J has built the infrastructure that has led to SPRAVATO's commercial success with thousands of clinics nationwide that now operate under a workflow that includes pre-dose checks, on-site administration and post-dose monitoring. BPL-003 fits directly into that structure with a similarly short in-clinic stay and no need for psychotherapy or specialized equipment. As you can see, this is a critical differentiator from the rest of the late-stage psychedelic pipeline. The short in-clinic time allows clinics to maintain predictable patient schedules, maintain high throughput and operate within existing staffing models. For patients that dramatically reduces the burden of care, instead of weekly visits, BPL-003 has a potential for 4 to 6 short treatment sessions per year without compromising efficacy. This is what scalability looks like in interventional psychiatry and AtaiBeckley is the leader. Now on the next slide, I want to highlight how the convergence of science, strategy and timing has put AtaiBeckley in this truly enviable leadership position. The pace of progress in this field has never been stronger, and it's clear that psychedelic therapies represent the next paradigm shift in the treatment of mental health conditions. Moreover, we're at a moment where regulatory clarity, clinical maturity and commercial precedent in psychedelic therapies are all converging. AtaiBeckley brings together the expertise, the clinical data and the purpose-built infrastructure to lead the shift towards second-generation psychedelic therapies. This alignment positions us uniquely to shape the future of interventional psychiatry. And now on to the next slide. We have begun 2026 building upon our successes in 2025. BPL-003's Breakthrough Therapy designation positions us for enhanced engagement with the FDA and a potentially accelerated path towards approval. And now we've obtained alignment on our Phase III program with the agency, as we'll discuss shortly. We have several important readouts and milestones ahead, including the initiation of our Phase III program and additional Phase II readouts across the pipeline. Following our M&A and IP expansion last year, our financing activities allowed us to end last year with just over $220 million in cash. Combined with our inclusion in the NASDAQ Biotechnology Index and successful U.S. redomiciliation, we're in a strong position to execute. Now we're excited to dive deeper with you on the BPL program and our commercial strategy. I'm excited to hand this off to Kevin to go through the clinical summary of BPL-003 and the upcoming BPL-003 Phase III design and plan. Kevin?

Thank you, Srini. Yes, I mean, we are excited to share details about our BPL-003 program, the progress we've made so far and the next steps to come. Many of you are familiar with the BPL-003 program, but we'd like to start with an overview of the key features on the next slide. BPL-003 is an intranasal dry powder formulation of mebufotenin benzoate. It's a serotonin receptor agonist with rapid onset and a short in-clinic monitoring time. Following positive Phase IIb results, where we saw rapid and durable effects after a single dose of BPL-003, it was granted FDA Breakthrough Therapy designation, reflecting both the strength of our data and the significant unmet need in TRD. After a successful end of Phase II meeting, we plan to initiate the first Phase III study in Q2 and the second in Q3 with final designs informed by FDA feedback. The FDA indicates their support for our proposed Phase III program reflecting a robust safety and efficacy profile across multiple Phase I and Phase II trials. In clinic, most participants were deemed ready for discharge approximately 2 hours after dosing, which if replicated in Phase III, could support higher patient throughput in established workflows, as Srini alluded to. Collectively, the combination of the strong data package, momentum for Phase III and a convenient dosing provides a strong foundation for us to continue studying BPL-003 in the future. Before diving into the Phase IIb data, I'd like to just take a step back on this slide to provide a quick background on the different routes of administration for psychedelic treatments. The treatment administration methods listed here can significantly shape a patient's clinical experience and impact how scalable treatment is in clinical practice. Among the options, the intranasal and buccal sublingual routes aligned most closely with real-world treatment requirements. They're familiar to clinicians, offer convenience to patients without compromising on predictable PK and a rapid onset, which are key considerations for scalability. BPL-003 uses an intranasal route of administration, which is important for its potential to be adopted in real-world clinical settings and to take advantage of existing interventional psychiatry workflows. Now that we've set the scene, let's look at the Phase IIb data on the next slide. As a whole, our Phase II data created a differentiated and well-rounded profile that gives us confidence in our advancement into Phase III. At a high level, we demonstrated that BPL-003 is fast-acting, durable, highly effective, well-tolerated and convenient in TRD. In the IIB, we saw the antidepressant effect of BPL take effect quickly with significant reduction in MADRS scores. The efficacy signal proved compelling and durable and with high response and remission rates. BPL was also well tolerated and provided convenient administration with only a 2-hour time to discharge readiness, supporting feasible real-world administration in a long-term maintenance setting. Let's walk through the Phase IIb design on the next slide. So our Phase IIb trial of BPL-003 was a randomized quadruple-masked study enrolling patients with moderate-to-severe TRD. Walking from the left of the slide, eligible patients were washed out if they were taking antidepressant medications and those that weren't -- were enrolled. All the patients were then randomized to 1 of 3 groups, either 12 milligrams, 8 milligrams or the control arm, 0.3 milligrams. The primary endpoint was the total MADRS score at day 29, change from baseline. And we followed patients up and took MADRS scores 1 day after dosing, the week later, day 8 and day 57. So that was really to establish the long-term durability of the effect. And then at the end of that core study, participants who are eligible could then roll over and move into the open-label study where they could receive a single dose of 12 milligrams of BPL-003. In addition to that primary endpoint, we had secondary endpoints, which included the MADRS change from baseline, as I mentioned, at day 2, week 4 and week 8 as well as the effect of 8 milligrams at week 4, and we also looked at response and remission rates. The design of the Phase IIb trial allowed us to measure both acute and long-term effects of BPL across the doses and repeat administrations, which provided critical insights into the timing of onset, the efficacy and the durability. On the next slide, we see that a single dose of BPL-003 met the primary end point. We observed a statistically significant change in MADRS score at day 29, with effects sustained up to week 8. For the 8-milligram arm, the MADRS change was minus 12 from baseline and minus 6.2 when comparing to the 0.3 control arm. The 12 milligrams was 11.2 change from baseline with a 5.3 difference compared to the 0.3 control. I want to highlight that the treatment effect was quite significant as early as day 2 which reinforces BPL's fast-acting profile. Looking at the blue and green lines on the chart, you'll note that the 12 and the 8 doses of BPL achieved comparable improvements in MADRS. The comparability is important because especially when we consider the safety data that we will talk through later on, which favored 8 milligrams. That combination of similar efficacy with a favorable safety profile is the key factor behind 8 milligrams as the Phase III dose. And I'll touch more on that in the following slides. When placed alongside external data sets for context, and we're looking here at an overview of the MADRS outcomes across clinical studies in TRD, we can see that earlier time points, the change from baseline in MADRS score versus placebo or control looks similar across the COMP360 and SPRAVATO trials. You'll note that the durability or rate of change over time is also quite consistent across the two COMP360 trials. BPL's week 8 durability appears encouraging. However, these are indirect comparisons and, of course, different study designs. So not head-to-head. However, the longer-term treatment effect looks quite different. The efficacy signal for BPL-003 shown in the green line here remains durable to week 8. This data suggests that BPL may offer a more durable effect following a single administration. But we do want to caveat that these obvious limitations to this comparison, namely that it isn't a head-to-head study, and we're comparing Phase IIb data to other Phase III studies where study designs differ. Before we move on to the open-label results, it's worth underscoring how patients actually move through the study. Not only did we see strong efficacy in the core phase, but participants who stayed engaged and the completion rates were high through both core and open label, and most who are eligible to move into the open label, chose to do so. The pattern of completion and rollover speaks to treatment experience that has proven to be practical and manageable from a patient experience standpoint. And that acceptability becomes even more meaningful as we look at how patients responded after receiving a second dose in the open label. Here, I'd just like to provide another glance at the IIb trial design, specifically focusing on those key details in the open-label study. As mentioned before, the open-label aimed to assess efficacy and safety of a second 12-milligram dose over a further 8-week period. And results from the next slide of the open-label here reinforce the durability and reproducibility of the BPL effect. After patients received a second dose, 12-milligram dose, we see an additional significant drop in the MADRS across all treatment groups. Even in patients who received the 0.3-milligram dose initially, the MADRS reductions were comparable to the antidepressant effects seen in patients who received 8 or 12 initially. More notably, patients who received an active dose of 8 or 12 initially showed a mean reduction in MADRS of 19 points at day 57 of the open label compared to the initial baseline. This data also helped influence our decision to take the 8-milligram forward. What we saw is something that we hoped for but didn't necessarily expect. Here, where the 8-milligram looked as good as the 12, giving us a lower dose with similar efficacy, which is always a good thing. Together, the significant MADRS reductions and durable effects tell us that BPL remains efficacious over the long term with repeat dosing prolonging and deepening the initial improvement. The next slide shows responder rates across the core and open-label studies, highlighting how responder rates change after administration of that second 12-milligram dose. On the left-hand side, responder rates during the core study reached the high 20s, low 30% range for the 8- and 12-milligram treatment arms. But importantly, after patients received the second dose, response rates significantly increased across all 3 treatment groups. The 8-milligram dose, followed by 12 appears to demonstrate the strongest response with a response rate of over 80% by the end of the open-label extension. The data here supports our dose selection decision for Phase III and we'll transition to that in the next section. Similarly, remission rates across the core and open-label studies showed a very similar pattern, the one on the last slide. We see a steady rise in remission rates after the first initial dose that increases more noticeably after the second dose was administered. Again, the 8-milligram dose followed by the second 12-milligram dose demonstrates the most efficacious and durable response compared to the other two treatment arms. Remission rates reached 67% for the group at the end of the open-label extension, which is a substantial increase from what was achieved in the core study. Just moving on to the safety and tolerability on this slide. We observed BPL was generally well tolerated across all doses with the vast majority of treatment-emergent adverse events being classified as mild or moderate in nature, and resolving quickly without intervention. What I'd like to emphasize on this slide is that when looking closely across the doses, the 8-milligram arm showed better safety profile than the 12, although both were very good with only one severe treatment-emergent adverse events, drug-related in the core study, the rest being mild or moderate. There were no serious drug-related adverse events reported in the core study and one serious drug-related adverse event reported in the open-label. The table on the left here lists the most commonly reported drug-related side effects, which were generally as expected. What is encouraging is that most patients were deemed ready for discharge within 2 hours after dosing, which also remains consistent with our expectations and supports the potential for a highly convenient dosing experience in the clinic. The acute effects of 8 milligrams appear to be less intense and better tolerated than 12. It is worth noting that the adjunctive benzodiazepines were available to investigators for agitation, anxiety but they were never needed, which gives us additional reassurance about the overall containment of the experience. In the context of the comparable efficacy you saw earlier, the balance between effectiveness and tolerability was a key driver behind selecting 8 milligrams as our go-forward dose for Phase III. To bring all this data together on the next slide, there are a few takeaways from our Phase IIb program. The study is the largest study of mebufotenin conducted and met both primary and secondary endpoints, providing a high level of confidence as we prepare for Phase III. Both the 8- and 12-milligram active doses of BPL demonstrated rapid and durable antidepressant effects and resulted in a short psychedelic experience that allowed patients to be discharged after just 2 hours in clinic. Across doses, safety was favorable with 8 milligrams showing preferable safety profile and comparable efficacy, which is a key driver. The full evidence package so far certainly warrants continued clinical and commercial development of BPL. And we're really excited to show you the details of our planned Phase III program next. So now let me move on to the next steps of the clinical development for BPL-003, the Phase III pivotal program. The pivotal program for TRD is designed to generate the clinical and safety evidence regulators and clinicians expect while informing commercial uptake assumptions. Both single doses and two-dose induction regimes will be evaluated and each trial will include a 12-week core study followed by a 52-week open-label extension, supporting assessment of both acute efficacy and long-term maintenance of effect. During the open-label extension, retreatment will be individualized and will occur every 8 to 12 weeks, allowing for flexible maintenance dosing. Efficacy endpoints will be evaluated by remote, independent, blinded raters, to reduce the possibility of bias and study participants will not receive psychotherapy during the study period, which helps isolate the pharmacological effect in this design. The Phase III program is broadly supported by several essential factors, including FDA alignment, breakthrough therapy designation and a robust differentiating characteristics of BPL, such as the short in-clinic sessions, robust efficacy and early onset and the potential for 4 to 6 treatments per year over the long term. Before we get into the Phase III program, I want to talk a little bit about the name ReConnection, which is what we've named our studies. We've heard from patients that treatment-resistant depression can feel like a disconnection from people, from daily life and from themselves. So the name ReConnection really reflects the core unmet need in TRD, helping patients to reengage in their lives, their relationships and themselves. And that is the outcome we're ultimately aiming to restore with our trials. On the next slide, we show details about the dual Phase III program, aims to reflect regulatory confidence and generate robust comprehensive data. The BPL-003 trial design reflects both regulatory guidance and real-world stakeholder requirements by incorporating a long-term open-label extension and large participant sample size for safety. These elements are critical for building confidence in key stakeholders around safety, durability and real-world applicability. Furthermore, by confirming the robust efficacy of an 8-milligram dose across two independent well-executed trials, we aim to strengthen our evidence package and reinforce dose selection decisions. Finally, the Phase III program is designed to support the flexibility and optionality of BPL over the long-term treatment by evaluating responder patterns and individualizing retreatment timing. These studies will clarify how BPL may be utilized in the real-world maintenance setting. Our overall approach to the dual trial Phase III program will broaden our evidence package across safety and efficacy, ensuring clinical adoption and commercial viability at launch. The details here on the next slide depicts how each trial plays a complementary role within the broader Phase III program. At a high level, both studies share the same overarching objective, to demonstrate rapid and durable antidepressant effects with a short in-clinic session while also supporting the potential for flexible individualized retreatment over the long term. ReConnection-1 aims to establish robust efficacy and characterize the dose response. It will be a 3-arm randomized double-blind trial, evaluating 8 milligrams and 4-milligram doses against placebo using a single dose induction. The 4-milligram dose produces a reliably perceptible psychedelic effect, but with substantially lower intensity and shorter duration than 8 milligrams. This supports its selection as the lower dose control recommended for mitigating functional unblinding while maintaining the potential to detect a dose response relationship. ReConnection-2 is a 2-arm study, comparing 8 milligrams of BPL against placebo using a 2-dose induction. The doses will be administered on day 1 and day 15. In both trials, change from baseline in MADRS total score will be measured at day 29, serving as the primary endpoint. Together, the two studies will allow the evaluation of two distinct induction regimens and strengthen the potential for flexible real-world treatment tailored to unique patient needs. This slide and the next slide provide detailed designs about the studies. ReConnection-1 is designed to replicate and extend the treatment response that we saw in the Phase IIb study and to further characterize the dose response relationship. Participants in this trial will be randomized 2:1:2 across 3 treatment arms, 8 milligrams, 4 milligrams and placebo, respectively, for a single intranasal administration of BPL or placebo on day 1. Eight milligrams has been prioritized as the optimal dose based on the prior Phase I and Phase II data, as I outlined earlier. The inclusion of the 4-milligram arm will allow for a better characterization of the dose response relationship. The primary goal of this study is a strong foundation for labeling discussions and commercial positioning. Reconnection-1, like ReConnection-2, will also include a 52-week open-label extension after the 12-week core part of the study is complete. The open label allows participants to receive individualized treatments with 8 milligrams every -- at 8- to 12-week intervals subject to predefined criteria. Incorporating a long-term open label extension was strongly supported by FDA feedback and is designed to generate the broader safety database needed for this chronic indication as well as to understand the maintenance of effect and real-world dosing patterns. Similarly with ReConnection-2, it follows a largely aligned trial design to the first study with a 12-week double-blind core followed by the open-label extension. This study will randomize participants 1:1 to receive a 2-dose administration of either the BPL or placebo on days 1 and 15. While ReConnection-1 aims to define the dose response relationship for BPL, the second study will test the clinical potential of a 2-dose induction regimen, exploring the potential to increase the magnitude and durability of the initial response and inform real-world induction optionality. The next slide shows the comparison of both pivotal trials and highlights how the overall Phase III program for BPL is structured to support a potential broad flexible label while maintaining and maximizing operational efficiencies. The core design elements across two trials, including primary endpoint and study time lines are intentionally aligned to reduce operational complexity and enable cross-trial data comparison. Together, these programs cover both single-dose and two-dose induction regimens along with individualized retreatment during the open label. Now let's look at the future for BPL-003. Minutes from the end of Phase II meeting showed that the FDA indicated support for the -- and provided constructive feedback on the overall design and the key components of the proposed program, including the overall size of the safety database. In parallel, we're expecting a readout from the Phase IIa Part IV study this year. This is the 8 plus 8-milligram 2-dose induction open-label study, which will provide additional insights that may inform future clinical and commercial planning. We expect top line readouts from both Phase III trials in early 2029, subject to enrollment and operational variables, which will directly inform launch planning activities and our broadband commercial strategy. Looking forward to the next few years, our key milestones reflect a well-planned and sequenced time line, which will position us for continued clinical investigation of BPL and future potential -- future approval and launch in TRD. Now I'm going to hand it over to Ryan, our Chief Legal and Business Officer, to provide an intellectual property overview. Ryan?

Thank you, Kevin. Intellectual property is a critical pillar of our overarching business strategy. As you just heard, we're breaking new ground in mental health treatment and it's essential that we protect our innovations to capture their full value. My team's mandate has been to ensure that each of our core programs is safeguarded by a robust patent estate. As we move to the next slide, I'll begin providing a high-level overview of how we're achieving this objective and why it matters, particularly for our lead asset, BPL-003. At the outset, I would note that our intellectual property strategy here at AtaiBeckley is comprehensive. Within this comprehensive strategy, we filed patents that cover both composition and method of use claims. And we craft those claims in light of and to align with each drug's target product profile, or TPP, as well as its intended labeling. In the simplest of terms, we look to protect what the product is and how it's used. Starting on the left-hand side of the slide, composition claims may seek to protect the drug substance, the molecule itself, including specific salt forms and polymorphs as well as a drug product such as the formulation or dosage form. These composition claims ensure that would-be competitors cannot make or use the same claimed chemical compound or formulation, but they do so only once these claims have issued, an obvious but key distinction and a point of strength for us here at AtaiBeckley. Notably, these composition claims are indication agnostic, meaning that they cover the compound or formulation regardless of what disease it's used for. As a specific example here in AtaiBeckley, we've successfully patented the benzoate salt form of 5-MeO-DMT also known as mebufotenin, and the inclusion of a key excipient, namely silicon dioxide in our proprietary intranasal powder formulation of BPL-003. In contrast to composition claims, method of use claims shown on the right-hand side protect the specific ways the product is used, which can include the indication as an example, in treating treatment-resistant depression, dosing regimens and even the route of administration in some cases. These indication-specific claims are vital in our field and particularly with respect to naturally occurring or known compounds. For instance, even though 5-MeO-DMT is a known substance, no one can use our proprietary 5-MeO-DMT benzoate salt intranasal formulation to treat depression here in the United States without infringing upon our issued U.S. method patents. This dual approach securing both composition and method claims tailored to the target product profile is key for effective market exclusivity. This approach also supports our Orange Book strategy wherein we align our patent claims with the final drug label so that the resulting patents can be listed in the FDA's Orange Book and thus get the full benefit from the Hatch-Waxman act. This Orange Book strategy ensures that if anyone tries to file a generic, they must contend with our issued patents, giving us the opportunity to legally challenge and potentially block entry of that generic until our Orange Book-listed patents expire. In summary, our comprehensive IP strategy is designed to leave no gaps. We seek to protect the innovative molecule, the precise formulation and device as well as their use in our target indications. And we do so with an eye for ensuring that we get full benefit from the Hatch-Waxman act. On net, this approach provides a strong foundation for commercialization of the approved therapeutic and multiple layers of defense, making it very difficult for competitors to design around our patents. Moving to the next slide. I'd like to specifically address the patent coverage we secured for BPL-003 here in the United States. Since that's our flagship program and our key market. As alluded to in the previous slide, and as we do with all of our programs here at AtaiBeckley, we have pursued a comprehensive IP strategy for BPL-003, including targeting key composition and method claims that are well aligned with and build upon the target product profile for BPL-003. We are very pleased with the results to date, both in terms of the strength of the issued claims and the duration of the issued patents that we've secured for this asset here in the United States. Diving in with a bit more specificity, we have issued U.S. patents to protect various 5-MeO-DMT compositions, including BPL-003's drug substance, namely the 5-MeO-DMT benzoate salt as well as other potential salt forms and polymorphs of 5-MeO-DMT. These patents currently have a lifetime out to 2041. Changing the focus to drug product claims, we also have issued U.S. patents on BPL-003's formulation as well as its route of administration. As discussed previously, one issued U.S. patent covers a proprietary intranasal dry powder formulation of 5-MeO-DMT combined with silicon dioxide as an excipient. This issued drug product patent provides us with Orange Book listable patent protection on BPL-003 to August of 2043, providing AtaiBeckley with an enviable period of potential market exclusivity. To cover future possibilities and consistent with our comprehensive IP strategy, I should also note that we've secured issued U.S. patents protecting alternative routes of administering 5-MeO-DMT, such as sublingual and buccal. Finally, and with specific focus on method claims, we have secured issued method of use patents here in the United States for treating depression with 5-MeO-DMT, which similarly last into 2041. Obviously, this slide is focused squarely on the issued patents we have achieved here in the United States. But our mission to transform patient outcomes by developing rapid-acting, durable and convenient mental health treatments extends beyond the U.S. and our global IP estate reflects these broader aspirations with strategic filings in major markets globally including Europe, United Kingdom, Canada, Asia and more. We have achieved patent grants in some of these markets, for example, in Europe and the United Kingdom, whereas others are in process. Where we secure patents abroad, we anticipate global patent protection time lines comparable to the United States. So where does that put us? To put it plainly, BPL-003 is very well protected, particularly here in the U.S., pursuant to a comprehensive IP strategy that provides for exclusivity potentially through the mid-2040s with patent term extensions. This strategy also allows us to deter generic challenges by listing these patents in the Orange Book at such time as BPL-003 is approved. Taken together, we believe that our IP strategy and our success to date in executing on that strategy significantly derisked the commercial potential of BPL-003, giving us confidence that if we reach the market, we can operate without generic competition for over many years, allowing us to invest fully in the product success now. With this backdrop, I will now turn it over to my colleague Kavita, who will discuss the BPL-003 commercial framework. Kavita?

Thank you so much, Ryan. And I'm really excited to be here, Kavita Panke, Senior Vice President of New Product, Planning and Commercial. And as Ryan said, I'll talk about the commercial vision and even our early go-to-market plan for BPL-003. So let's take a look at the landscape we're operating in. Treatment-resistant depression, as we've heard, affects a huge number of people. And yet the market remains largely untapped. So the STAR*D trial showed that 1 in 3 individuals with major depressive disorder do not respond to 2 or more oral antidepressants. That's millions of people, 3 million to 4 million adults in the U.S., if not more, who are left without effective options. So there has been progress. SPRAVATO has made meaningful inroads. But even so, it has reached less than 3% of those who qualify for TRD treatment which means over 95% of people with TRD are still not receiving an FDA-approved therapy. And so why is that? When you look at the patient experience, it's really not surprising. People need treatments that work quickly, that last, and that don't require them to reorganize their lives to take these treatments. Frequent clinic visits, where they can't drive, must arrange support and lose hours of their day, create significant barriers that many just simply can't overcome. The burden of accessing care has actually become part of the disease burden itself. So there is a real paradigm shift underway in psychiatry and one that moves us from simply managing symptoms to actually enabling durable, meaningful change. I've actually worked in this space for a pretty long time. And what we're seeing now, it feels different. It actually feels transformational. So if we look on the left side of the slide, today, our tools are chronic antidepressants. They do help, they help many people. But they come with real limitations, slow onset, often taking weeks or months before we know whether they'll even work. Chronic side effects, and some of the most problematic like weight gain, sexual dysfunction, sleepiness that drive people off the treatment. And the burden of daily dosing or in the case of esketamine, SPRAVATO, frequent clinic visits that still require ongoing chronic administration. Ultimately, these treatments manage symptoms rather than creating lasting or root level change. Patients remain stuck in a cycle of maintenance and managing symptoms. The vision for tomorrow looks very different. Psychedelic-based interventional psychiatry offers the potential for rapid efficacy. You could know within 1 day or 2, whether it's working for you. It offers the possibility of durable benefit paired with intermittent rather than chronic dosing. And it opens the door to neuroplastic change addressing underlying biology rather than just the symptoms. The future we're moving toward is one defined by rapid results, durable efficacy, infrequent dosing and the potential for lasting change. So why BPL? You heard from Srini, from Kevin's deep dive into the data. But the story is actually very simple BPL-003 has the potential to deliver what I call a trifecta that TRD patients have been asking for. It looks fast, it's durable, and it's convenient, together in one treatment. So here's what the data shows so far. Rapid improvement with a single dose showing effect by day 2. Durable benefit with a 6.2 point placebo-adjusted modest reduction at week 4, and this effect was sustained for 16 weeks in the open-label study for most patients. And true convenience, requiring a handful of treatments over the course of the year in 2-hour clinic visits. And this matters because it expands who can realistically access this care. People with demanding jobs, family responsibilities or long distances to travel, people who have been effectively shut out of current treatment-resistant depression treatments, they finally have an option that works for them, a trifecta of improvement. So when we look at BPL against the competitive set, so the current standard of care as well as pipeline opportunities. It has a credible path to be best-in-class positioning, because it is the only asset in the category that aligns with the three attributes that consistently drive adoption and reimbursement: rapid-acting; durable; and convenient. And of course, importantly, while we cannot make direct comparisons without head-to-head data, the landscape makes the differentiation quite clear. Oral standard of care, as I mentioned before, often slow onset, many don't respond to the drugs, and chronic daily use limit both effectiveness and adherence for patients. Esketamine, SPRAVATO, very meaningful innovation, but durability remains a challenge for many. We hear this quite a bit from clinicians who use the product as well as from patients. Roughly half of patients require biweekly or even weekly maintenance dosing, creating ongoing costs and operational burden. And the long-acting psychedelic pipeline programs, multi-hour in-clinic dosing sessions can introduce staffing, throughput and scalability real constraints that will slow adoption and limit reach. So why is BPL positioned to lead in this space? It's the only program that aligns across all three high-value attributes: rapid, early onset of effect; durable sustained benefit without chronic maintenance; and convenience. A small handful number of short 2-hour sessions rather than multi-hour or weekly commitments. The implication is straightforward, a treatment that delivers speed, durability and low operational burden expands the addressable TRD population and reduces friction across patients, providers and payers. This combination is rare in psychiatry, and it's why we believe BPL has the potential to truly reshape the paradigm. So let's double-click into the current standard of care for TRD, SPRAVATO and the durability of effect in the induction phase. And keep in mind, once again, this is for illustrative purposes only and no head-to-head studies have been conducted. What this graph attempts to do is it juxtaposes SPRAVATO's primary efficacy data, a change in MADRS total score from baseline, from their monotherapy trial against the BPL-003 Phase IIb 8-milligram data. What you see here is a comparable MADRS response curve, which took SPRAVATO 8 dosing sessions versus a single dose for BPL. And so think about that, compound that annually, and that's a lot of time, in-clinic dosing sessions, and health care utilization that is potentially saved with BPL-003. So what we can directionally conclude here is that SPRAVATO takes 8 doses to achieve a similar efficacy result that BPL can potentially achieve in a single dose. Now let's shift and look at the maintenance therapy component. Based on an analysis of real-world SPRAVATO data, we note that about 70% of patients are being maintained on at least one dosing session per week. And the majority of patients are on the higher dose, 84-milligram dose by treatment session 6. So what you see on the left is the assumed annual cost of SPRAVATO and this is WAC-based pricing. What this translates to, if you put together the actual real-world utilization compared to the WAC prices, the real world cost is on the upper end of the $60,000 to $65,000 range. So when we think about BPL, of course, it's early to provide any pricing guidance at this time. However, SPRAVATO is the best price anchor we have today. And if we deliver on our trifecta of value, similar or better efficacy with a single dose, rapid effect and convenient 2-hour dosing model. We believe there could be opportunity for premium pricing. Our goal is to build a treatment model that puts patient safety and convenience at the center without requiring in-session psychotherapy and that can be deployed within today's interventional psychiatry infrastructure. So what I'm describing and what you see on this slide is not our clinical trial protocol, but it's our vision for real-world implementation with the specifics that will ultimately be guided by the data we produce. So this model mirrors familiar in-clinic workflows used across other therapeutic areas, making it straightforward for sites to adopt and scale. So let me just break this down. There's the preparation session, where patients meet with their provider for education, expectations, questions, standardizing readiness and reducing variability. Then there's the dosing day. Patients come in, they check in, they move to a private room and receive the nasal spray dose from their provider. A trained health care professional remains with the patient throughout their experience. And there's efficient discharge. We anticipate a roughly 2-hour post-dose observation window similar to SPRAVATO, enabling predictable scheduling and higher clinic throughput. And then importantly, a follow-up visit conducted either in person or remotely, ensuring continuity without adding burden to the patient. And I want to underscore no psychotherapy requirement. So there's no need for specialized therapists dramatically reduces cost, staffing constraints and operational complexity. So to summarize, our vision is a model that is simple, familiar and resource efficient, lowers barriers for providers, expands the number of clinics that can participate and increases patient access, especially in markets where staffing space and reimbursement are real constraints. BPL-003's short in-clinic model creates a fundamentally stronger economic and operational profile for patients, providers and the health care system. So in an 8-hour clinic day, a 2-hour dosing window allows a provider to treat 3 patients per room, compared with one in a, let's say, 6-hour long session psychedelic model. Observation revenue is effectively the same, right? 6 total hours per room, so the real economic difference comes from the drug revenue. And in a buy-and-bill environment, the margin on drug administration far exceeds the margin on observation time. In fact, observation alone often doesn't cover the incremental staffing and monitoring costs. So the takeaway is without meaningful drug revenue, interventional psychiatry simply may not be sustainable for many clinics. And the equation becomes straightforward. More patients dosed, more drug administered, more clinic revenue. A shorter sessions directly increases throughput and makes the model economically viable. So I want to address three key advantages and real-world examples of a short in-clinic model. First, higher throughput and greater access clinics can treat more patients per day, opening the door to serving that 95% of TRD patients who currently aren't receiving an FDA-approved treatment and giving clinics more flexibility in scheduling. Real-world practicality for patients. Let's think about this. A full day in-clinic model is unrealistic for most people. Life happens. There's work, there's child care, there's transportation, there's delays. If a clinic books one patient per room per day and that patient is late or needs extra time, the entire day collapses. A 2-hour model can really avoid this fragility. And reduced provider burden and burnout, expecting a provider to remain engaged for 6 to 8 hours straight may not be feasible. Breaks, turnover and fatigue are real constraints and actually, caregiver burnout is already a growing issue in psychedelic monitoring. So shorter sessions dramatically reduce that strain. So across economics, operations and patient experience, a short in-clinic model is simply more scalable. It supports stronger clinic economics, increases patient throughput and lowers the burden on staff, which I think are key ingredients for broad adoption. So next slide, BPL-003 supports a lean, highly targeted commercial model because the TRD interventional psychiatry market is already very concentrated and built on existing infrastructure. The treatment fits directly into current workflows, making it a true plug-and-play offering. So there's a concentrated prescriber base. So of the 6,000 to 7,000 REMS-certified SPRAVATO sites today, our data suggests that about 10% account for the majority of prescription volume, about 75% of the total volume. And so taken together, a really focused field force under 100 representatives can cover the highest value centers that already understand interventional psychiatry, did the hard work of organizing their clinics and are comfortable with similar models of care. I want to talk about operational fit. These clinics can run SPRAVATO and BPL side-by-side potentially using the same room staff and processes. And that level of operational overlap is just not possible with long in-clinic psychedelic therapies that require dedicated rooms and multi-hour sessions. And market readiness, we are actively building as we speak, the ecosystem with clinical leaders, high-volume practices, payers and patient advocacy groups to ensure early seamless adoption at launch. So this combination of concentrated demands, operational compatibility, and ecosystem engagement positions BPL for efficient, scalable commercialization. So I want to conclude here. We are laser-focused and invested in treatment-resistant depression. But TRD is just the beginning for BPL. Beyond that, we are strategically exploring adjacent psychiatric disease areas that have scientific rationale, high unmet need and strong commercial potential. And as Srini mentioned in the onset, we also have a portfolio of exciting candidates to support optionality and broad impact in mental health. So with that, we will take a short break and then I will come back, and I am super thrilled to introduce and to be able to participate in our next session, which we brought a set of panelists, experts, key opinion leaders in the field, Doctors Feifel, Wilkinson and Dr. Hendricks, who will have a chance to introduce themselves and their practice. And we'll talk about and share real-life perspectives on treatment-resistant depression, interventional psychiatry and the true potential and adoption of these new class of therapeutics. So thank you so much. And with that, I think we are going to a short break. [Break]

Hi, everyone. I think we're back from that short break. And maybe I'm biased, but I think this is going to be a really great part of the meeting and a great conversation. So as I mentioned before, we went for break, but I'll reiterate, we are very excited to have three psychiatry key opinion leaders in the U.S. join us this morning for this session. And I'll -- in a moment, I'll let them introduce themselves. But the goal is really to really understand real-world treatment patterns, how we think about the treatment landscape and the pipeline potential and just real-world experiences on managing these patients. So with that, we have Dr. Feifel, Dr. Wilkinson and Dr. Hendricks joining us. And maybe I will start with Dr. Wilkinson, if you can just introduce yourself where you practice and talk a little bit about your practice and the patients you see, and yes, and anything you want to share in your intro.

Sounds great. Thanks for having me here, Kavita. My name is Sam Wilkinson, I'm Associate Professor of psychiatry at Yale. I'm the Medical Director of the Yale Depression Research Program. I help run a combined research and clinical entity. The clinical service is a pretty busy interventional service. We do a lot of ECT, a lot of ketamine and/or SPRAVATO and a growing number of TMS treatments. In a given week, I think we have about 80 slots for either ketamine or SPRAVATO so those 2-, 2.5-hour slots. So yes, that's a little bit about me. I'm grateful to be here.

Sounds great. Thank you. Welcome. Dr. Hendricks, why don't you go next?

Hi, I'm Peter Hendricks. I'm a clinical psychologist, University Professor and Endowed Chair in the Department of Psychiatry and Behavioral Neurobiology here at UAB. My work centers on psychedelic approaches for mental health conditions. I've done that now for about 10 years, which is hard to believe. And I focus on depression, substance abuse disorders and related challenges. I have a practice here at UAB and also collaborate on clinical trials, provide consultation in academic and research settings. And I'll just say briefly that TRD patients I encounter or study typically have failed multiple antidepressant trials, 2, 3, 4 or more. They present with moderate-to-severe symptoms and span a broad demographic, working age adults often with comorbidities. And in our region, we see a mix of insurance types, commercial, Medicare, Medicaid and uninsured or self-pay which influences access to interventional options.

Great. Thank you so much. Thanks for being here. And Dr. Feifel?

Thank you for having me. So I'm a board-certified psychiatrist and a Professor Emeritus at the University of California, San Diego. I'm also a founder and CEO of interventional clinic called Kadima Neuropsychiatry Institute. I was a very early and enthusiastic adopter of interventional psychiatry. I think before it was -- before we described it as such, I started actually the first -- the very first ketamine clinic outside of research back at UCSD in 2008 and started doing TMS around that same time, when it was FDA approved. So I was very eager to move into different types of treatments that had been sort of dominating psychiatry for the previous half century. And in 2017, I gave up my tenure position to open up Kadima, and we do probably also about 80 treatments a week of either IV, IM, ketamine and SPRAVATO intermixed and sort of same treatment rooms, we do a very robust TMS program and a very large number of clinical trials, mainly with psychedelics.

Great. And maybe we'll start off with -- there was quite a bit in the session before about TRD sort of representing a large population of patients, yet this practical factors, convenience factors, things like that, make it sometimes difficult for these patients to access more of the interventional treatment. I'm wondering if you guys can comment a little bit more about that. Are there practical considerations that influence maybe what type of treatment you try next for these patients or if they are going to be able to adhere and stay on these treatments? If someone wanted to comment on that or I can pick on someone, but I'm sure there's a lot to say.

I can speak to this briefly. I'll start off. So we really started expanding our ketamine service prior to SPRAVATO FDA approval, probably around 2015, 2016. And this was in line with a very busy existing ECT service. And some of the executives we had to convince them that, look, we're not going to rob Peter to pay Paul. And that was not at all what happened. Our ECT service has not suffered. So I think that speaks to the principle that there are just a lot of people -- and clearly, ECT is one thing. There's a lot of people with TRD who were not getting treatment with ECT, which prior to SPRAVATO and ketamine was one of the only things for TRD. A lot of this is related to the clinical profile and the side effect profile of ECT, but also the inconvenience of not being able to drive and so forth. You have that a lot with SPRAVATO. But it speaks to the principle, there's a number of patients out there that are not getting interventional treatments. And I think in part related to these factors of convenience and so forth.

Great. Anybody else want to comment on that?

Yes. People often ask me, including patients, what -- how do you decide? Which intervention, TMS, SPRAVATO, IV, ketamine. And the answer is that often it's driven by the practicalities of each of those. First of all, ketamine is not covered by insurance, so there's a practicality of finances driving that treatment option. And then between TMS and SPRAVATO, they have different logistical requirements both of which are -- represent an inconvenience to patients, but it depends on which fits better. So one requires daily short treatments for a long period of time, 6 to 9 weeks, and they can drive each way. The SPRAVATO is less frequent but frequent twice a week for a month and once a week for a month and as needed each time longer sessions, 2.5 hours typically, and they can't drive. So somebody is -- it really depends on sometimes it's really just one is a nonstarter for whatever reason. So it is much as we wouldn't like it to be, we'd like it really to be driven by precise personalized clinical decisions, it's often just a matter of pragmatics.

Yes. Dr. Hendricks?

I'll just add to that trying not to be redundant, but to give some sense of the scope of the issue here just in Birmingham, Alabama, which is a relatively small city, the metro area is maybe 1 million. UAB likely has 15,000 patients with depression and 30% to 50% of those are TRD patients who cycle through several oral medication trials sometimes for years before interventional therapies enter the conversation. And as noted, this delay stems from stepwise guidelines, insurance requirements, patient provider hesitation around options that are viewed as invasive or require a fair amount of monitoring or travel as noted. I'll be honest, I'm excited about this new option on the table, potential new option on the table, especially if it can facilitate conversations around earlier intervention, when this rapid symptom relief could be critical to prevent functional decline, hospitalization, suicidality. I just don't think I get to overstate the burden of prolonged inadequate response. It's just -- it's substantial. And I think tools like ketamine, esketamine and TMS are helpful for some. They've been shown to interrupt the cycle for some, but I'm personally not satisfied with the response and think we need something better. And not only something better that -- but something that occurs earlier could really improve outcomes and quality of life.

Yes. That's great. Thank you. And to this conversation, in your opinion, what are the key unmet needs? Like there's been a lot of innovation, right, in the space, in general, in depression, MDD. There's a lot of options in your toolbox. But what are -- we highlighted some earlier, but in your opinion, in your practice, I want to hear what are kind of the key unmet needs, especially for these refractory patients?

I always tell people in the space that there are kind of three factors. One is overall efficacy, the other is speed, and the other is side effects. And if you're trying to develop a new therapy, and it doesn't get at least one of those, then you're not really going to add value to what is in existence. And going back to this theme of convenience, with these novel interventional/psychedelic treatments, I really do think some of the true issues, again, assuming that they all have pretty good efficacy, which is mostly seeming to be the case. There's maybe some questions about that. But the two factors, and I think you've already brought this up are how long is the monitoring and how frequent do patients have to be dosed. That will just determine so much of the logistics, so much of how clinics are able to adopt this. What -- as you pointed out here, and we recently learned from the there was a large analysis of the SPRAVATO REMS data that so many of these patients are coming in weekly, as the most common frequency of treatment. And so a lot of the clinics just fill up right? They don't have openings for new patients if they're treating all their patients weekly or so many of their patients weekly. So that's another aspect. I mean, SPRAVATO, it was slow in the beginning for the first couple of years, and it really has taken off is as people learn how to adopt and implement this. But clinics just fill up in part because really the most common dosing frequency is weekly. So again, the three clinical factors enhance efficacy, rapid onset and improvement in side effects and then the two logistical factors. How long are these intervention treatment is going to take for observation and then how frequent do you have to redose. So much hangs on those factors.

Yes. Thank you.

I would definitely agree with Dr. Wilkinson about those three factors. I mean, those are the big three. And just to elaborate a little bit on them. Right now, with the relative innovations we've had in the last decade or two with TMS and ketamine, they really represent sort of somewhat of not overlapping very stark contrast that sometimes is dilemma for patients. The SPRAVATO can work fast, not as fast as it's the drug that was inspired by, ketamine, but it's not durable. So just to get it going, you need to come in 12 times over 2 months and then as Dr. Wilkinson mentioned, most people need to come in for maintenance on a frequent basis, not uncommonly once a week. I actually spoke to a patient yesterday that wanted to talk to me because she had done amazing with SPRAVATO until she was forced to go to once a week, because that's the label and she's now on maintenance for once a week with insurance won't cover more than once a week. So the durability is not very good. On the other side, the TMS is not fast, although the durability is better, but then you have patients who are extremities. They're really in a difficult situation and need fast relief. So right now, we have these two treatments and you got to choose speed or durability and to be able to combine both would really, really be sort of an advance in the field. And I just want to make two other quick comments. I mean, Dr. Wilkinson mentioned side effects. And I don't think that was really emphasized sort of in the presentation that when you're taking a drug every day, you're a prisoner to the chronic presence of the drug is -- sorry, of the drug in your body and those side effects when you're taking a drug once periodically, maybe every quarter or so and then no drug is in your system. I mean, that is a tremendous paradigm shift in the ability to kind of not suffer from those side effects. And the last point I want to make is we talk about efficacy improvements. And we always think about this thing called TRD, which has a very specific definition of failing two antidepressants. But ask most patients who don't meet that criteria who will say -- and failing is usually not being -- not having your depressive symptoms reduced by more than 50%. So if you have a 55% improvement in your reduction in your symptoms, you're not treatment resistant, but ask those patients who aren't treatment resistant because they do get more than a 50% improvement, whether they are satisfied with their antidepressants. They'll say no. I still suffer a lot of symptoms although it's better. And no, the cost I pay is side effects like numbing or libido. So we talk about this group of 1/3 of patients on medications who are on TRD, I think almost 100% of patients who are on the conventional medications would be interested in something that allows them a more complete symptom reduction and freedom from the side effects required produced by taking daily dosing.

Yes, I would agree wholeheartedly with that. I think most patients on SSRIs or SNRIs would say they feel a little better, not much, and there are a list of unpleasant side effects, often weight gain and sexual dysfunction, which are very unpleasant, sort of at the top of the list of side effects you'd rather not have. I also wanted to mention that many of the patients that we see are socioeconomically disadvantaged. So any intervention that requires frequent visits can be a significant burden and can, I think, add to the sense of demoralization that nothing is quite working and what's suggested next is a rather significant investment of time and energy. And as noted, the response is just not adequate for many and the durability is variable. So there's clearly something that we need that can respond to the sort of demanding and sometimes chaotic lives that many people lead something that can be, as noted, not only durable, but rapid and that can be done in an efficient way.

Great. And with that, I do want to segue into the tomorrow, let's say, right? So the new potential intervention, the therapeutics, the psychedelics that are emerging, there seems to be kind of the longer-acting in-clinic programs and then the short acting. Can you talk a little bit about just your thoughts around that, how you see these playing together in the real world? And what are sort of the your practical kind of thoughts around those long versus short in-clinic times?

I don't know if we have an established order. I could break the model here and go further...

Let's do it. Yes.

I think this is a really interesting question. And I mean, the truth is we just don't know if the length of the experience is tied to more durable or more robust response. I think an argument could likely be made based on a limited number of animal studies or basic science studies but we just don't know. And I think at the moment, I would argue at least that for me to use a much longer-acting psychedelic, let's say, there's got to be a really good argument for that because it's otherwise, as noted, very inconvenient for the patients, very resource-intensive and it's just going to limit scalability substantially. I think that shorter-acting compounds just have a tremendous advantage in that they work well with clinic workflow. So it's just -- it's unknown. And I think BPL-003 here is really unique because the mechanism of action might in fact, be unique, not only in that it's shorter acting, but the mechanism of action at the brain level might be different than other psychedelics as well that could give it a substantial advantage. But right now, I'm just -- I'm not sold on the idea that a longer experience is in any way more beneficial, but we'll have to see at the moment, a shorter-acting experience is far more practical.

Anyone else have thoughts on that?

I would say that I absolutely agree with Dr. Hendricks. And I would not have predicted this. I would have -- if you had asked me at the beginning of this revolution we are in studying psychedelics, it's is a longer trip. I'm going to produce better results. I would say, yes, it's nothing else, just sort of a longer exposure of the brain to this. And the results are proving my prediction wrong. So it's really interesting. It's the beauty -- that's beautiful about science, it teaches us things. So -- and that's great. That's great because obviously, it's self-evident that shorter subjective experiences or a quicker recovery time is an advantage. And it may mean that the duration at least is not important or it may mean as Dr. Hendricks pointed out that BPL-003 has some advantageous mechanisms of action allowed us to produce comparable efficacy to some of the longer agents that we've seen in studies without that longer experience.

Yes.

I think also -- from a clinic consideration, there's the economics of this, right? If you have an 8-hour observation period, there's going to have to be a pretty substantial reimbursement for the clinics to want to implement these. And even aside from that, the logistics of dedicating 2 staff to one patient, the economic considerations for long versus short acting are quite disparate.

Yes. And to that point, Dr. Wilkinson, do you see like a BPL sort of slotting and given -- assuming that it sort of has that 2-hour dosing paradigm, the already established SPRAVATO sites. Could this sort of be a slot into that infrastructure kind of a plug-in sort of thing? So we talked about that in the presentation, but just wanted to get any of your thoughts in terms of how that kind of infrastructure and kind of economic piece sort of would fit in.

I would say very likely, yes. So I alluded to this earlier, but it took a long time for SPRAVATO to get taken up into practice, I think, because practitioners had to change their infrastructure, the way they approach this, the buy-and-bill modeling as well. It's not something they were used to. So there was a lot of kind of weed whacking going on to kind of forge that path. And there's inevitably going to be some with an agent like this. But assuming it's approved, it's going to be much, much, much easier because that path is there than if you had to start it from just the jungle, so to speak.

Yes. Anyone else have thoughts on that topic? All right. So I want to shift gears and maybe talk about BPL. I mean that was, of course, the focus of the presentation and Kevin and Srini provided some of the clinical information around that program. And I know a couple of folks. I think David and Peter, you guys have experience with the product from a clinical trial perspective. Would love to sort of get your thoughts from what we heard from what we saw this morning and with your experience. What do you think about the data? What aspects do you think are particularly meaningful interesting, maybe differentiating from what you've got today in your toolbox?

Well, I'll jump in. I'm really stoked about the data. I mean, the efficacy was so great. So it hits all the marks, rapid onset durable. I mean, the study was 8 weeks, and I think Srini pointed out that at 8 weeks, it was holding steady. We may be seeing only a slight decrement whether that was a trend or not. So we really don't know how long a single dose last, but we know it last at least 8 weeks and it wasn't looking like it was about to poop out quickly. And what also was interesting was that I don't really recall any other study where the peak effect wasn't at 24 hours, an interesting phenomena with BPL-003 was that the subsequent time points showed even a greater separation from placebo, especially with the 8 milligrams. So this is something, again, may go back to the somewhat unique mechanism, pharmacological mechanism. But usually, the way we think of psychedelic is like they blossom right off the bat and then it's a slow wilting over time, but BPL actually grew for the first couple of measurement points and then kind of started to hold steady. So I just -- who knows how long it's going to -- that's super cool and it's everything you would want if you were to put it in an order for a drug to treat depression.

Yes, I'll add to that, too. So I would first say since I'm a scientist first and foremost, I try to always maintain a very skeptical view and influenced by a famous philosopher, Karl Popper, who would say, you really need to bend over backwards to prove yourself wrong. And if you fail to do so, then perhaps you've had a success. But as I would be with any clinical trial, I was skeptical and really pleasantly surprised at the results for a number of reasons. As we noted, the rather rapid, rather robust and durable effects were really wonderful to see. But also the safety profile was fantastic. And I say that in part because there's always going to be in the psychedelic world, some degree of use that occurs outside of controlled medical settings, naturalistic use. And it's unclear what's happening in those contexts. But now I'd like to say that the difference here would be akin to having a cavity filled in a dentist's office versus having a cavity filled by me in my basement. These are completely different things. You wouldn't want me filling your cavity. And I think the things that happen naturalistically can sometimes scare me. But I think, again, these are completely different things. And the sort of concerns I may have had from the kind of unusual things that you see in the wild did not at all generalize to this clinical trial which was rigorous and objective. And despite my most skeptical view, I think we had data that really pleasantly surprised me. And like David, I feel really quite enthusiastic and excited now.

That's great. And when we think about patient types, patient characteristics within treatment-resistant depression, any characteristics or subpopulations come to mind that you think or maybe that you've seen in the clinical trials that can potentially maybe benefit from short-acting or BPL or that kind of thing? Like anything that sort of comes to mind at all?

Well, I'll just jump in really quickly because I have a thought. I mean the first is all potentially. I don't see any who wouldn't be considered. But the one thing that jumps to mind since so much of my work is with lower income patient populations that this could be especially beneficial given the time demands are significantly reduced.

Yes. Any other thoughts on that one?

I'd just say to follow up on that, a 2-hour treatment is feasible without having to give up a day of work, right? I mean we have a lot of patients who do SPRAVATO, but they just -- they couldn't give up the work. So they'll come at one of our later appointment times 4:00, 5:00. And so they get in a full day of work for the most part and then they do that. But with some of the longer ones, that's just not possible. I mean you're calling out for the full day if you do -- if you need to be in the clinic for 6 to 8 hours.

And one of the things, I think, David, when you and I had chatted about a little bit is even in this the clinic sort of the staff burnout and the need for maybe additional staff or longer hours for the staff based on a longer sessions. Any thoughts? Is that -- I feel like that theme is sort of coming up more and more, right, even just the caregiver burnout, and that type of thing for such long hours. And any thoughts or comments on that issue?

Right now, the requirements in the clinical trials are that the facilitators are licensed therapists. And so I assume that's probably going to be the requirements, at least initially when these drugs are approved. You have to think about that, that for a licensed therapist, that's a full day of clients that it's an opportunity cost, a big opportunity cost. And if you have -- like we contract our facilitators. So they -- I don't think a lot of them are willing to do it on a regular basis like multiple times a week because they wouldn't be able to have a practice, right? They have to be there for their patients, right? A 2-hour intervention or even doing two of those and still having half a day is much more practical to work into their to work into their professional careers.

Kavita, I'll say also, I think I have now personally administered psilocybin to close to 100 participants and was the lead therapists for many of these sessions, and they're demanding, they're long and they can also be characterized by like moments of significant anxiety on the part of participants, and it would not be unusual for someone to ask to leave. That's always anxiety provoking for the therapists. We certainly don't want anyone eloping the room, especially when their consciousness has been altered. But those sessions are challenging. Now obviously, I think there could be a place for psilocybin as well, but 5-MeO-DMT is not just shorter acting psilocybin, and I think it's unique in many different ways, and it might be especially appropriate for certain mental health conditions like TRD. But I will say as someone who has administered psilocybin and been a part of these sessions, 5-MeO-DMT was a refreshing change, less demanding on us all. And I have to say like, in some ways, quite gratifying because to the degree that it was appropriate for me to observe this in some of these trials, I saw with my own eyes, participants who appeared to be depressed in every way at 8:00 a.m. and by 9 or 10 I saw a different person in front of me, someone who's animated, smiling and talking. And it's just remarkable to see like almost to the point, as I mentioned, as a skeptic, you can't believe what you're seeing.

That's actually a really good point. You can -- being an investigator and being responsible for assessing patients before they're leaving the clinic, you do really see a difference at the end of these sessions. I mean, patients are drained at the end of the long -- maybe they've been in this room. They've been -- the experience has been much longer, and they're really emotionally drained. I mean even if they have a great -- even if it was a positive experience, and they'll have a therapeutic effect. It's depleting to be -- to have a 4-, 6-, 8-hour subjective experience and also be in the same room and very different with BPL. It's almost like you come in for a visit, you do it and leave much more akin to our ketamine treatments where people are actually just more energetic when they leave because it wasn't such a draining logistical experience and subjective experience.

And Dr. Feifel, could I just follow up the -- when you -- the ketamine, the esketamine rooms that you have, do you see using those same rooms potentially for a product like BPL? Or would there have to be some changes or things like that? And of course, it's a matter of the data and what we see in the ultimate REMS program. But just curious on your thoughts around that.

Absolutely. In fact, we have rooms that are differently configured and larger for our clinical trial subjects because for the most part, those are longer sessions. And in the ketamine rooms, we have just -- patients are sitting in a chair, nice, comfortable reclining chair. Whereas if you're going to be around for 8 hours, you need to have a bed option, a chair option. You're having a facilitator present who also can't just stay in one place. So we have rooms that were designed with the idea of these longer treatments, but had they been two hours, they fit in perfectly with our ketamine treatments or SPRAVATO treatments. We could have used -- we could use those moves.

Great. And I think -- oh, Peter, I think you are on mute.

Sorry about that. I just wanted to add too, and this is coming from a place of like excitement, obviously, and optimism. But even when we're conducting studies with psilocybin to administer two or even three doses in a week would be pretty demanding on everybody. But my first thought after being a part of this Phase II trial with Beckley was, we could, in the clinic, administer several of these administrations in a day. So it's not just a matter of sort of practicality but also just sort of a psychological effect for the interventionists. I think that's something that would also be easier for them to do.

Just had another practical thing that isn't obvious unless you're sort of been doing these kinds of things, cancellations happen. We typically ever -- we do 15 ketamine/SPRAVATO treatments a day with multiple rooms being used concurrently. And cancellations happen and it's a 2-hour slot, but if you have a long treatment and a patient cancels for whatever reason, you can't. It's not something you can fill quickly because it requires people to have a -- like prepare for taking a whole day off. That's a huge economic loss, right, the cancellation. And also, with the 2-hour session, you can't, on fairly short notice, fill that slot because patients can say, okay, I can come at this afternoon whereas that would not work if the whole session is 6 or 8 hours.

Yes. That is a fantastic point. Well, this has been great. I'm going to wrap with a question that I think you've all sort of got to in some ways. But how do you see in this future state, there are a number of innovations and options, hopefully, that are coming to market, patients definitely need new options. Well, how do you see BPL kind of fitting in? What's the positioning? Are there -- that broad patient base of TRD that are not currently still maybe cycling through oral antidepressants, is that an opportunity? What is sort of the -- where do you see this kind of fitting into your treatment armamentarium? And maybe I will pick on Dr. Wilkinson to share some thoughts on that.

Yes. So I think it will be a question of -- so taking out economic consideration, really, what I mean is third-party considerations and coverage and prior auths. Taking that out, I think it's a question of where does it fit with respect to ketamine and/or SPRAVATO. Certainly, if the data from Phase II, hold out for Phase III, it's a lot more convenient initially, there's going to be some hesitation with provider because it's a new thing, right? It's -- but I could envision where it goes first for a lot of patients, again, in part because of those very practical considerations. And if things unfold the way Phase II would indicate much, much less of a burden on time and so forth. And there probably are going to be patients who, again, sort of come out of the woodwork, so to speak, like I started this with talking about how when we started launch a fairly large clinic in SPRAVATO/ketamine, it did not eat into our ECT patients because there was a number of patients just not willing to get ECT, but are still struggling. And I think that's probably going to be a similar thing, right? I mean the TRD population is anywhere from 1.5 million to 7 million people in America, depending on how you define it. And I think there's about 60,000 people who have had SPRAVATO. So there's a huge, huge portion who have not, for whatever reason, because of distance, because of accessibility or because they're like, yes, you just can't do twice a week for 4 weeks and then once a week and so forth. So it's not always a necessary competing. But those patients will, so to speak, come out of the woodwork and say, yes, yes, yes, I could potentially do this treatment. So it does remain to be seen, I think, where it falls in line in the sort of treatment algorithm with respect to ketamine and/or SPRAVATO. But I can definitely see it coming first because of practical considerations alone.

Thank you. I'm going to do a final roll call. David, any thoughts on that?

I think Dr. Wilkinson really articulated it really well. I mean I think that I'm not one of those people who think that we're going to find great differences in different psychedelic agents across different indications. I think there's going to be a set of indications that psychedelics are for. And for the most part, they're going to be cross-indication efficacious with maybe some nuances. So I look at the results of BPL in TRD. And I see this is not just -- I see this as sort of probably representative of what we're going to see in those other indications that psychedelics are going to be useful for including anxiety and PTSD and things like that.

Great. Dr. Hendricks, any final thoughts from you?

Well, I'll be brief, but I think BPL could occupy a niche for rapid durable interventions with convenient administration. And it could potentially serve as a bridge or alternative to existing psychedelics or interventionals and time will tell. But I think the niche there is ultimately for rapid, durable and convenient administration.

Great. Well, thank you so much. With that, we'll close out this session. You guys have been great, some really, really good real-world feedback and so really appreciate you guys being here. And I'm going to turn it over to Jason for the rest of the session.

Yes. Great. Thanks, Kavita. Now I'll ask AtaiBeckley's team to also join here along with our key opinion leaders. We have a number of questions that came in, so we're going to start kind of going through those, and I'll pass those along to the appropriate people here.

So to start, there's some questions that came in from Andrew at Jefferies. Srini, I think I'll put this to you and perhaps Kevin to follow up here. He said, I know that you've said you've run two Phase III studies or will run two Phase III studies, we'll stop. That said, during your EOP2 meeting, did you ask the FDA if that Phase IIb can be a supportive pivotal study? And what did they say? Said another way, why wouldn't the Phase IIb be counted as one of the two supporting pivotal studies?

All right. Thanks, Jason. Actually, let me start by thanking the panelists. It's great to see all of you, and it was a really exciting discussion and clearly appreciate your support and enthusiasm for BPL-003. So to answer the question around pivotal. So it's actually a more nuanced question than one would expect, right? So let me start by saying that the Phase IIb trial was met with a lot of enthusiasm at the agency. I mean it's always going to be viewed as a supportive trial, no matter what you do. And when you go to file an NDA, it's really the totality of data that is the key. So I've always said it's going to be two trials. The reason was this anticipation about what would be needed for a safety database, right? So the product is being dosed intermittently but it's being dosed intermittently in a chronic indication, right? So these folks are anticipated to get these drugs for an extended period of time. Just as we saw with SPRAVATO, right? I mean, that's why you needed a safety database. But that said, what are you going to file with is a slightly different question. So let's just assume that one trial was quite robust. And for whatever reason, the other one was not, you would still file, right? There's no doubt about that. You are looking at the totality of evidence, again, highly supportive trial, a clear win on one of the Phase IIIs that is what you're looking for. And then, of course, nothing adverse and there's nothing fancy or nothing special or magical about 0.05 if that's partially what's behind this question. You basically do need that totality of evidence. And I don't know, Kevin, if you've got anything to add to that.

No, I think you've summarized it well. I mean, the safety database is primary and actually having two trials that answer slightly different questions, I think, is also very helpful. So I mean, the landscape is, of course, changing. But I mean, importantly, we had this meeting and we got our minutes back after publications came out that suggested one trial approvals. I think that this is something that we may face later on. But for now and really for the safety database, we need to keep both.

Great. Maybe a follow-up question or a slightly separate question. But as we think about some of the trial differences between the Phase II and Phase IIIs, you're evaluating this at a longer time point. You're using a placebo now. One of these studies is doing 2x or the induction dosing, 2-dose induction dosing. So shouldn't the efficacy delta look even better in Phase III compared to Phase IIb? Can you talk a little bit about your confidence in that scenario happening? And I'll put this, again back to perhaps Srini and then, Kevin, if you want to follow up on that.

I mean we're obviously pretty enthusiastic about the design, right? So there's been certainly talk in the space about a potential efficacy delta, affirmative delta that happens when you go with a true placebo versus the low dose. It's speculation at this point. But these are bigger studies. We do have the 2-dose induction. We've got the actual placebo. So we're obviously pretty enthusiastic about the results. Now can we say that we're going to -- are we going to power it differently? Are we going to expect something? I don't know. It's hard to say that right now. We don't have that data. We haven't got enough data from competitor trials, but still, we're pretty enthusiastic.

Yes. And I think -- I mean, I'd just add, I mean, the 4-week endpoint is important. I think that's proximal to dosing. And I think that was something we're really keen to get in. But as you say, Srini, I mean, I think there is a sort of factors in our favor, perhaps the 2-dose induction placebo comparator, but bigger trials, more variances often. So I think our assumption is that these may balance out and we'll be in a position to be pleasantly surprised if not.

Yes. The 4-week endpoint, I think, is worth reiterating. That is -- that was an important win. It was an important piece of insight that we gained from other programs that are out there, right? So SPRAVATO did use a 4-week endpoint. Others in the space that tended to use something that's a little bit later, specifically 6-week. Just bringing that in closer to administration for the first trial, replicating what we did in the Phase IIb is kind of critical. And of course, it does reduce the time from the second dose to the assessment. Of course, that doesn't change anything about durability. We've talked a lot about durability. Of course, these trials do, in fact, measure durability out to 12 weeks. So none of that changes, but bringing that primary endpoint into 4 weeks. I think certainly is -- it certainly helps put things in our favor.

Great. And maybe one more question here before we get a few questions to our doctors on the line as well. So both Phase III studies are now using a placebo. Could using a placebo work in your favor compared to an inactive dose. And the Phase IIb had a sub-active or sub-perceptual control of negative 5.8 points on MADRS. Would you expect placebo to show the same in these Phase III trials something higher or similar? Just if you could comment a little bit around that.

Look, I mean I think I'd sort of err on the same side of similar. I mean clearly, there are confidence intervals on those effects. And we're doing another trial. We're going to replicate that. I mean I do think prior evidence in other trials has suggested that an active control may dilute the treatment effect slightly. But I think the accuracy of estimation only gets better with repeat trials. So again, I think it would be nice to be in that position, but we're not banking on that certainly in our trial designs.

Okay. Great. I'm going to take a little bit of a different angle here. So Dr. Wilkinson, Feifel and Hendricks, we'll kind of go to you for these. And there's a number of questions that came in. Maybe a few repeats a little bit, but slightly nuanced, I think questions here. So the first one being how prepared is the interventional psychiatry ecosystem to operationalize BPL-003? Are practices that provides SPRAVATO ready or getting ready to incorporate psychedelic-based therapies into their practice? So that's a question for all 3 of you. Maybe I'll pick on Dr. Wilkinson to start.

Yes. And I spoke to this earlier, but I guess the best way I can answer is they're going to be much, much more ready than they were for SPRAVATO. If the 2-hour time frame holds, it's going to be much, much easier to incorporate this into a practice that is already using SPRAVATO to treat TRD. Maybe some slight modifications. Obviously, a lot of it depends on how the Phase III data unfold. But if the 2-hour holds, it's slight modifications, but it's going to be much more fast out to do than it was to get SPRAVATO off the ground.

Well, I would definitely agree with that. I think the adjustments needed to pivot from SPRAVATO to a drug like BPL, are relatively minor, not 0, but relatively minor. The adjustments needed to pivot from SPRAVATO to a full day experience psychedelic are substantial.

I think you are on mute, Dr. Hendricks.

Sorry. It's challenging for me. I was going to mention also, if psilocybin is approved in late 2026 or early 2027, there's likely some paving of the way. And in this case, with an intervention that's a bit more or a lot more time intensive. So there could be a fair amount more readiness than we anticipate, but as mentioned, certainly more than ketamine.

Excellent. And maybe a little bit of a follow-up question here, but again, in a slightly nuanced way. Another question we had that came in was, has SPRAVATO increased interest in interventional psychiatry from a provider perspective, such as from your colleagues that have been practicing in the conventional way for years and also from incoming residents and/or fellows for individuals, trying to understand if infrastructure and practitioners will be there to facilitate growth of interventional psychiatry with the introduction of psychedelics? Maybe we'll start with...

Yes, I'll start off. I think the answer is a clear yes. I mean SPRAVATO is inextricably linked with ketamine and the excitement that, that has generated and really, it's continued and just kind of expanded with the so-called psychedelics kind of whatever you want to call this renaissance that we're in the midst of. So there's a lot of interest. And within 4 or 5 years of SPRAVATO approval again, about 60,000 patients treated with ECT. TMS has been around since the mid-2000s and there's probably around 120,000 patients treated. So I think very quickly -- and I don't think one is eaten into another, really. Again, I think it's just prior to SPRAVATO, TMS, the landscape is essentially ECT, which is a very, very important treatment, but there's a lot of cultural baggage. There are some side effects that many patients are unwilling to risk with ECT treatment. So yes, it's just -- it's expanded interest. I think it's expanded in the number of treatment centers that offer interventional services in one form or another.

Maybe go to Dr. Feifel next. Any additional comments?

Yes, in terms of the question of whether it's increased interest or -- I mean, I don't think providers think of it that way, like, oh, this is making me think about interventional psychiatry. But what I do see is that there were providers who -- obviously, those of us who were doing ketamine, it was just a seamless transition. But what was interesting was there's a number of providers now who still don't do ketamine because it was a bridge too far, the whole idea of intravenous and fairly deep experiences. But when SPRAVATO came on board, especially also the FDA approval, I think gave them that level of comfort and it was much more of a -- I think of a stretch for them. So what we do see clinics now who are kind of doing mainly traditional things and have been sticking with traditional prescription med management that didn't join the interventional but have now adopted SPRAVATO. I think a lot of providers don't think of it even as interventional as that large of a shift in their practice is just, okay, I can do this. And that's interesting because it lowered that bar to adapt a new treatment.

Dr. Hendricks, anything else to add?

Again, trying not to add anything redundant. Look, I would say that the emerging literature on psychedelics has led to an increase in enthusiasm for psychedelic like SPRAVATO. Aside, a major medical center, say, like UAB will have an independent clinic dedicated to psychedelics separate from SPRAVATO. And there is no shortage of residents and others who want to know now how can we prepare ourselves for real-world use. And I anticipate we'll have a very active clinic that will be engaged with patient populations and training residents and collecting real-world data. So I would even say it's SPRAVATO aside, the literature on psychedelics alone has led to an increase in enthusiasm and conversations around preparedness.

Excellent. Thank you. There's a few other questions here. Maybe I'll ask two questions are pretty similar. So how do doctors see patient appropriateness for psilocybin versus 5-MeO versus ketamine? And perhaps a related question here is for your existing SPRAVATO patients, what would the clinical evidence need to look like to prompt the switch to psychedelic-based option? And perhaps Dr. Hendricks, I'll start with you on that one, just to mix things up a little bit here.

Well, okay. So I'm a psychologist, keep that in mind, not a physician. I would work closely with physicians to determine medical appropriateness. But sort of from a psychological perspective. My sense is that given the intensity of the experience of psilocybin or as Dr. Feifel said, how sort of -- I don't want to say burdensome, but just that it can be a lengthy and tiring experience. It likely requires a bit more preparation and likely psychotherapy. I don't think that, that is the case. In fact, we know that isn't with BPL. So my first thought is that the big differentiation, again, is that we have a shorter acting, more convenient and scalable approach with BPL, and therefore, it might be more appropriate for people who are eager for a more convenient treatment.

Dr. Wilkinson, anything to follow up there?

Can you repeat the question? There was a lot packed in there.

Yes, of course. Kind of a two parts. So it's how do doctors see patient appropriateness for essentially the different approaches of modalities, psilocybin, 5-MeO, ketamine and kind of the follow-up there is for your existing SPRAVATO patients, what would the clinical evidence need to look like to prompt a switch perhaps to a psychedelic-based option?

I'll maybe start with the second question. And I would say I think the clinical evidence needs to look somewhat like SPRAVATO, right? If it's way less effective, then there's going to be a lot of hesitation. But the logistical factors are in favor of the -- a drug like BPL. We hit on these themes several times already. So if you're having to choose between a session twice a week for 4 weeks and then once a week and then something like that after indefinitely, or once every 2, 12 -- excuse me, on treatment every 8, maybe 12 weeks, that just looks a lot different logistically. So if you're close to SPRAVATO evidence in terms of both, I would say, delta and overall improvement in something like a MADRS, then that's going to be -- with your logistical factors in your favor. I think that's going to be in your favor. The first question, how do doctors make decisions about whether -- I don't think you can answer that one right now because all these things, except for SPRAVATO are still experimental. So doctors aren't faced with these questions. The doctors that are involved are running clinical trials and it's very protocolized and so forth. So there's really not any evidence or in my sense, in my opinion, that can help kind of open the window into doctors' decision-making about these treatments.

And maybe as a follow-up there, let's just kind of envision making treatment decisions if and when multiple psychedelics are on the market. What perhaps would kind of feed into that decision-making, effect size, depth of psychedelic experience, the safety profile, patient preference? I just kind of maybe talk through a little bit about the criteria there that you would potentially use.

Sure. Sure. So I know -- I hate to sound like a broken record, but some of the factors that I mentioned maybe an hour ago, so overall efficacy, speed of response, side effect profile on the clinical side, and then the logistical side, right, how often do I need to get retreated and then -- and how long are the treatment sessions. So within those 5 factors, I think a lot of decision-making will hang on those 5 factors.

Let me kind of flip the question to a sort of a different perspective. A lot of what drives patient -- sorry, providers' decisions are what their clients are demanding, right? So envision a future where, let's say, a current SPRAVATO provider is now faced with approved psilocybin, approved formulation of, let's say, LSD and approved BPL. And the data are kind of -- we project from what we've seen on those compounds so far. And providers are -- especially psychiatrists are conservative. If they're doing something and it seems familiar, there's momentum, inertia, I would say, to not necessarily change. Well, they're going to have a lot of patients who are going to be reading about these newly approved things and they're going to be -- you're saying, why can't I have one of these, where I come in once every 4 months or so, instead of coming in like every week or every 2 weeks to get -- just to maintain. And if that provider is a little -- is going to push back on that, they're going to see that client -- they're going to not see that client. That client is going to go to another place, right? And then if we take that further among the agents, if you -- so we need to do is we need to think from the patient's perspective, this is a different world than even 20 years ago, patients are exposed to this stuff. They're aware, they research. It comes in front of them on their smartphones. And so which one are you going to be like especially interested in among the -- you're definitely going to want to switch from SPRAVATO, so you don't have to come in all the time. Then among those psychedelics, which one are you going to pick? I mean, obviously, there's going to be differences by the time all these programs are done in some of the efficacy and the REMS and so forth. But all things being equal, a big factor is going to be how long do I need to rearrange my life to be in the clinic. So what are patients going to be demanding from their providers? That's what's going to make the decision.

All excellent points. I really appreciate that. Let's maybe take a little pivot here. To Srini and then maybe as a follow-on to Kevin, what are the key assumptions that lead to an early 2029 top line readout from the Phase III trials for BPL? This is coming from Sumant from Canaccord. So maybe Srini, you can start there and then Kevin?

Okay. Sure. Yes. I mean, obviously, we have a lot of experience within the team at this point in getting these trials up and off the ground. And over some shifting time -- some shifting regimes as well. So it's been -- we have the requisite experience to really kind of understand time lines around this. There's still some things that can be unknown. Obviously, at this point, we are being conservative on our estimates. And of course, over time, we'll be -- as these trials progress, we'll be providing some additional updates as to when top line can -- when we anticipate top line. I don't know, Kevin, if you have anything to add.

Yes. No, just to double down on that really. I mean, I think the two global Phase II trials have taught us a lot in terms of getting drug into country Schedule I substance is a thing but I think we've got that well worked out. We know a number of really good sites and investigators. And so I think that helps us a lot as well. So I think we've really -- we're sort of in the best place. It's something we've done before. But as you say, I think we really need to get those details lined up, and I think we should guide later on.

And Kevin, maybe as a follow-up there, a 2-part question here. Would the company consider that time line as conservative? And is there a potential for an interim readout for one or both of these studies?

Yes. I think it's realistic. And as I say, some of the unknowns will resolve themselves like getting drugs into country and getting licenses approved and that sort of thing. But I think it's a realistic time line based on our prior experience and this indication. And again, in terms of the readouts, what we're talking about here are the top line results for the core study, those are the 12-week double-blind phases for both studies. So we haven't guided any further on that, and we'll probably update as time goes by.

Okay. Great. And maybe staying with you here, is another question that came in is, what have you learned about staffing from the clinical studies you've ran so far? And how will that translate in real-world practices? How many monitors per patient? Could one staff member oversee multiple rooms? And what kind of credentials would likely be required?

Yes, that's a really good question. And I think one that is certainly, as an industry, we're working on quite carefully and I would certainly separate out what we need to do in a clinical trial versus what has to happen in clinical practice. So in the clinical trial, we are still learning about this drug. We're still gathering data. And the regulators have got some clear guardrails around what should be done. So certainly, we need one qualified monitor to support the participants through the trial through the dosing day. And we need a backup person. It doesn't necessarily have to be in the room, but needs to be nearby and sort of there to step in if necessary. Now again, we have a shorter dosing duration here. So it's not that people have to take comfort breaks or that there's a very long session. But I think that is what we envisage for our Phase IIs. As I say, that's one monitor in the room. And I think that is going to evolve over time. I don't think it's going to be less than one person in the room. Again, we have clear guidelines from regulators about what those qualifications need to be. But I do think that in time, we will have a better understanding of what the core competencies for this role are, what the training is that is required. And I think that will begin to define what the qualifications need to be. So in some ways, again, given the experimental nature of these compounds at the moment, it is important to err on the side of caution, and we have been cautious in terms of the qualifications. And that will change as clinical practice adapts and learns about these drugs. And I mean maybe I can turn that over to the doctors on the call as well. And I don't know if there are any kind of comments or additions that you'd add to that.

Kevin, I think your point about the clinical requirements versus clinical trials is very poignant. But of course, a clinical practice often ends up being influenced by clinical trials because the FDA tends to especially with drugs like psychedelics where there's going to be REMS often requires that the clinical practice replicate what was shown to be safe and efficacious in the trial. So we can assume that -- and since I've been doing these studies, I've seen a very, very dramatic downgrading of the monitoring requirements. I think the companies are pushing for less and the FDA, as they see, the safety is agreeing to less. So the first studies that I was involved in always had two fully licensed therapists -- licensed and specifically trained in the room. Now at this point, the standard is one licensed, qualified trained facilitator and one backup who's monitoring can -- who will be monitoring remotely on site, who is not licensed, especially. So unless that changes, that may be what the requirement is. In clinical practice with a drug like BPL, if I use SPRAVATO as a model and ketamine, we can definitely monitor multiple patients simultaneously without a person in every room. That's what we do with our ketamine clinics. We have 4 or 5 patients that are monitored by CCTV. We have wireless blood pressure vitals and patients as needed. We have nurses and physician to go into patients as needed, especially after the first line. Maybe for the first experience it's new, there's a lot of anxiety, you might need a monitoring. But once patients kind of become familiar, they're coming in for their quarterly or 4-month dosing, they can -- for 2 hours, they can definitely be in the room without somebody from a clinical point of view, and being just monitored by a less than 1:1 ratio. So we'll see that will probably happen as the drug is out and AtaiBeckley and other companies are able to show good, safe results, those REMS may loosen over time.

I'd like to just add one point to that. I think the short durations psychedelics are particularly well suited, I believe. And of course, I'd like to get the take of the KOLs on the line, but they're particularly well suited to having less monitoring. And the reason for that statement is that if you look at the data that we've generated, the really -- the most intense period of the psychedelic experience is very short for these drugs. I mean we're talking about this 2-hour thing, but that is wheels up to the wheels down. That's everything, right? If you're looking at what we refer to as SERS, which is Subjective Intensity Rating Scale and things like that when you're in the 5 and above range, for BPL, it's, what, 30 minutes, maybe 40 minutes. If you think about like a psilocybin or something, it's several hours, right? So it's many fold longer even. So that may allow us less monitoring over time. I mean it's just -- you can watch the patient, you can watch them remotely if something is going on, go in there and settle them down as appropriate as opposed to having to talk them through in a really extended period of time. But again, I throw that out to the KOLs to get their reaction to that.

I'll speak to that a little bit, not only the monitoring, but just the physical infrastructure demand. It may not be an obvious problem. But if you have an 8-hour session where patients are in an altered state. One of the -- how do you get patients to go to the bathroom, right? When long-acting psychedelic companies approach us and say, hey, we want you to run these trials, said, okay, you have to have this special space, and there has to be an adjacent bathroom because we don't want patients who are in an altered state stumbling through the hallway and interacting with other patient. And you don't have that same problem with if you're -- if by 90 minutes, 98% or whatever percent of the effect has resolved as your Cmax data suggests, it's not really that much -- most human beings can wait for 90 minutes. So that is another aspect to the -- just the logistical facility that a shorter period allows for.

I'll take that one step further. On the monitors end, if the FDAs would require a licensed facilitator to be in the room at all times. If you -- and this is something you don't foresee, but when you get -- when you start getting dent into the weeds of the study and you're thinking of the logistics, you realize you have an issue because if you have a 6 or longer hour session, those monitors need to take a break, right? And if you need some -- that means you need to have a backup available. And let's say like us, if we're contracting, that's a serious problem because you're paying for somebody who's going to be stepping in for short periods of time to give the monitor a break to go to the bathroom or to grab something to eat. Whereas if it's a 2-hour, a single monitor can do that. You put a half hour gap between patients. They go to take a break and they can go back in for 2 hours without needing a break in between. So little things like that, that are not obvious from the surface make a big difference in the economics.

I may add to that, too. So as I mentioned before, I'm a psychologist, you might wonder how a psychologist became interested in drug development. And I would say that it started with psilocybin and the impression or intuition that psilocybin could lend itself well to adjunctive psychotherapy or that some sort of preparation is needed, some sort of so-called integration is also needed. And then it could be helpful to have a trained mental health professional in the room, especially when difficulties arise. I think in the case of BPL, it's a completely different ball game. I don't think Atai is trying to make me redundant or put me out of a job, but I don't think I'm needed in this case, although I still find the subjective effects, the experiences that people have to be fascinating and the mechanisms are incredible. And it's really amazing to hear the sort of stories that people have and to see this sort of rapid transformation. But I do think again, a rather significant upside is that the psychotherapy really may not be needed at all, which may not be a win for me as a psychologist, but certainly a win for the patient populations, and that's what I want more than anything else.

That's wonderful. Great conversation there. Maybe another kind of general question come in and Srini I'll pose this to you, and then maybe Ryan as a follow-up as it pertains to scheduling actually. So how is AtaiBeckley working with lawmakers to reschedule DMT? Will this be done prior to approval or after approval? How long will this take? And there are a number of organizations that are proponents of advancing psychedelic therapies? What type of role are they playing in general? And are they helping to lay some of the groundwork for scheduling of these drugs? So Srini, maybe you can take that. And then Ryan, if there's any follow-up there.

Yes, absolutely. So let me start with kind of the sort of the statutory process here, right? So what does Schedule I mean? It means that it's a drug that has an addictive profile and also has no approved medical use. That latter part is really key. So what typically happens, and this has happened before for things like Gamma-hydroxybutyrate, but also THC. What happens is that the drug gets approved by the FDA, and the FDA then petitions the DEA with an analysis called Eight Factor Analysis, et cetera. The DEA then -- typically, it's kind of a -- by definition -- well, the definition has shifted then, right? It's been approved. So the DEA will then down-schedule that product. So going back to Gamma-hydroxybutyrate, that is still a drug abuse, it's still Schedule I, but as in its approved form of Xyrem, it is down scheduled. So just that product is down scheduled. The compound itself is not. So we're not necessarily advocating for DMT itself per se to be down schedule. We want our products, whether it's DMT or 5-MeO-DMT, et cetera, we'd want our products, the BPL-003 and VLS-01, just like COMPASS presumably wants COMP360 to be down scheduled, not psilocybin per se. So it's a slightly nuanced answer. Now the DEA approval process statutorily is 90 days. So once the drug is approved, that is put forward by the FDA to the DEA, that's a 90-day process for them to do the differential down scheduling. So that's the general thing. But I'll actually let -- hand it off to Ryan here to kind of give some of the -- some additional color as well as some of the organizations and some of their efforts there.

Absolutely, Srini. Thank you. I think you nailed obviously the big picture framework. The only thing I would add is that running parallel to the federal effort, of course, is also the state-specific efforts. We're actively engaged with APP and other psychedelic developers to ensure a systematic approach to communal development challenges, including descheduling. I would say that our general view at AtaiBeckley is that we need to be and will be actively engaged in the lead up to commercialization to ensure that the amount of time and friction between a potential FDA approval. And the -- again, as you said, narrowly tailored descheduling at the state level is maximally reduced so that the patients get the benefit as expeditiously as possible following approval. I would say the only other thing to add we do anticipate having the benefit of following certain longer-duration psychedelic developers like COMPASS Pathways with COMP360, which will presumably help us refine our specific approach to this issue for BPL-003.

Great. Thank you, Srini. Thank you, Ryan. Another question here is, and Srini, I'll pose this to you and then Kavita. Is Atai entertaining any conversations with big pharma or other potential partners to distribute or commercialize the product? Just maybe talk through a little bit about what potential commercialization might look like there?

Yes. I mean, obviously, we can't speak to any conversations until they become -- until they get to a certain point. But big picture, there has been a lot more inbound interest in this space. And I think a lot of that was driven, of course, by SPRAVATO's success over the past couple of years. So there's -- it's -- the interventional psychiatry pharmacotherapy space has really kind of hit the radar screens for many companies. So there's definitely interest from that perspective. And of course, the other catalyst here was AbbVie with the Gilgamesh transaction a little while ago. So those are things that really have driven it. And we will see and of course, we'll advise appropriately as things change there. But I'll actually let Kavita kind of talk through the commercialization bit, which I think is unique for us here such that it's not a requirement really to have a big pharma partner for commercialization.

Yes, absolutely. Thanks, Srini. And I'll bring back some of the commentary I had earlier. We are fully prepared to commercialize alone. And I say that because this is a market -- I shared some data. This is a highly concentrated market in treatment-resistant depression, interventional psychiatry. And even just looking at the SPRAVATO numbers, I think it's remarkable, we think about the 80-20 rule, this is actually 10% of the sites today that are treatment centers that are REM-certified SPRAVATO treatment centers are actually yielding the majority, 75% of the prescriptions. So I think that, again, it sort of underscores that there is a very concentrated high-volume treatment center opportunity here. And because of everything that you've heard today, we believe that the operational fit within those -- that current infrastructure makes a lot of sense, and we are uniquely fit to slot into that. So yes, we are definitely preparing for commercializing alone and developing those relationships and market readiness as we speak to be able to do that.

Okay. Great. So I'm going to move on to another set of questions from Pete from Cantor. Kevin, maybe there's a little bit of a repeat here, but perhaps we can just talk to this a little bit. But for the Phase III studies, are you using sites that are psychiatry experienced, but not necessarily psychedelic experience? If so, what specific training or monitoring will you put in place to ensure consistent prep and dosing day procedures, some examples being patient prep, handling acute effects, discharge criteria, et cetera.

Yes. Look, I think the first aim is to use as many of the sites that we have worked with before who are not only psychedelic experience, but I think understand the BPL product or the VLS product. So I think that's our first step. But there will, of course, be others that haven't worked with BPL before. I think we are really benefiting from the fact that there has been a great capacity build due to the other Phase III trials that are ongoing at the moment. So kind of globally, we are seeing greater bandwidth in the number of sites. That isn't to say that we aren't because of competitive influences at the sites, we aren't going to take some sites that are new to this endeavor. And again, we've stood up a number of psychedelic naive, but very experienced investigative sites on previous trials. I think there are a couple of things that really help us here. The first actually is the central rating. So that is consistent. So our primary endpoint and our MADRS scores. I think the central rating, although it's operationally complex, really helps us. And obviously, we supervise that very carefully, and we do surveillance of those scores, but we have fewer raters and there is more consistency. We also have a very comprehensive participant support manual and training program, and that actually has got some patient-facing elements to it. It's also got some training of the monitors. And that's a key piece. So I think making sure that the monitors are trained because actually that they deliver the support in a consistent way is an important piece. And that really speaks to expectation management, sort of equipoise around dosing and uncertainty and that sort of thing as well. So I think there's a lot of effort that we put into managing that process. And of course, we record those sessions, and we do assess those as well for consistency and quality, and we remediate if we need to. And I think the other part is on adverse event monitoring. I mean, this is a sort of a strange place to be. People have rather kind of strange or difficult to describe adverse events. And so again, I mean, I think the field has really evolved as we've grappled with this problem, although it's not new. I mean, I think Esketamine, SPRAVATO had it, there are a number of other compounds that have dealt with similar things. But I think making sure that we capture those adverse events in a way that is interpretable across sites. And that's not really a new site, old site problem. It's just a quality issue that we are very focused on. So I do think we're pretty confident that we'll take a sort of small percentage of new sites, but that we've got an onboarding process that is well set up to accommodate them.

Move on to another question here. So I'll start with Srini and then I think it would be really good to get our KOLs also to comment on this. But in a real-world practice setting, what would drive retreatment or redosing with BPL or other psychedelic agent? Would it be patient-driven with patients reaching out to the clinic if symptoms occur? Maybe just speak a little bit about that. So Srini, maybe I'll start with you and perhaps Kevin to comment on that, and then I think it would be great to have our doctors on the line also.

Yes. So we are -- there's been several points where we got some -- had some interesting discussions with the agency that we are keeping close to best because for competitive reasons. And obviously, some of this will be disclosed over time. The specifics on the retreatment criteria is certainly one of those things that we don't want to get into in detail at this point. We have obviously mentioned that it can be 8 or 12 weeks. And -- most -- to the best of my knowledge, all the competitors are actually focused on 12 weeks. But because of the short duration -- the short duration nature of BPL-003, the question is, can you actually help patients that are basically kind of losing efficacy sooner. It's an option that may be available to us because of that short duration. So that's the only thing that I think we can say in terms of the details. But I don't know, Kevin, if you want to add anything to it. Otherwise, we can defer to the KOLs for how things happen in the real world.

Yes, I think that's right. I wouldn't really say much more about that. I think having some flexibility, and we've got obviously a sort of a range that we're thinking about, but the data will really drive where that lands. But I'll hand it over to the clinicians for your thoughts as well.

Well, I think that -- I think there's going to be parameters probably driven by FDA REMS and insurance. So with TMS, there's usually a minimal interval period before an insurance payer will be willing to reapprove another round with SPRAVATO, for example, I had mentioned that typically, once a week maintenance is maximal, which some people -- given its short durability isn't enough. From a clinical point of view, there's 2 models. One is reactive when -- so when a patient starts to feel that they are losing some of that benefit. Given those other parameters are eliminated now, we just -- so somebody starts to feel they're drifting back, they call, they come in, which happens a lot with ketamine clinic because it's out of pocket and people don't want to be scheduled regularly if they're doing well, they'll kind of play it by year, especially if they get a point where they can go fairly long duration. And then there's a further prophylactic model where you're scheduling it to prevent any relapse. And I think that probably what will end up happening if it's driven by clinical need, patients will figure out where their pivot point is when they need to come back and those will be kind of scheduled in advance. So mine lasts about 3 months and then I start to notice a decline. So I schedule out in 3 months because they want to be in the books for that.

And I'll just agree with that all and add to that also perhaps the point for enthusiasm here, at least on my end is the ability to intervene earlier before there's a sort of a lengthy period of demoralization after trying one SSRI or SNRI or some other treatment after another that really doesn't work. So there will be parameters, as mentioned, but I think we should be optimistic about being able to intervene earlier and prevent that lengthy period of demoralization.

I'll add on with respect to what David said about the reactive versus the kind of preventive approach, I think the reactive works pretty well for SPRAVATO because the interval is so short. You're seeing patients maybe once a week, once every other week, most in our clinic once every 4 weeks. But I think it is going to be -- that is going to be one of the slight shifts that I think would be important for patients to where if you get a dose of BPL, maybe you have a telehealth appointment that you schedule for 4 weeks from then. And then -- and you kind of assess where they are maybe 8 weeks from then and try to kind of -- before patients really fall back to the depth of the point that they were before, try to catch them as that slope just starts to to become negative a little bit and you can get them in quickly. So that's my thought about the react. And again, the SPRAVATO will lay a lot of the groundwork there will have to be some tweaks as to the best treatment model that providers can offer.

Excellent. That's very helpful. Moving on here, and Kavita, I think I'll send this one to you. There's a question that came in. Given the rapid onset and relatively short session time of BPL, what do you see as the minimum durability threshold needed to compete with the 20, 30, 40, maybe even 50-plus annual SPRAVATO visits is 3-month durability a win?

Sure. I would say unequivocally, yes. When we think about and we shared some information that on average, SPRAVATO patients are on weekly maintenance, biweekly or weekly maintenance. So think about it coming into a clinic with the same 2-hour duration, same constraints, but every other month, that in of itself is game changing, and it was validated. We talked to a lot of patients. We talked to a lot of -- we did some research on this, and they absolutely echo those comments. So while an even broader treatment frequency even better, I think every other month is absolutely a win, as you said, for patients as well as for clinics.

Appreciate that. Maybe going back to our clinicians. The question that came in that BPL reproduced its Phase II clinical profile in Phase III, what proportion of your TRD patients would you recommend this for? What patients would be good candidates versus SPRAVATO, for example? Maybe Dr. Feifel, it looks like you came off mute first, so we'll go with you.

I mean, assuming that it's SPRAVATO versus BPL as we know it from Phase IIb, I mean, who would I not -- I mean I'm trying to think of why I would recommend somebody stay on SPRAVATO. Nothing is coming to mind. I mean you can do -- get these great effects generally quicker and longer duration. I mean I have to think hard about some situations where that wouldn't be a no-brainer recommendation. And even if I didn't recommend it as soon as the patients got wind, they'd say, "Hey, are you going to be buffering this year" because I'd much rather come in once every few months.

And I would agree with that. My response to that question would be all, obviously, considering the sort of inclusion and exclusion criteria that are already a part of the trials and the REMS, but I don't see any reason why we would recommend esketamine before BPL. In fact, I'm more enthusiastic about BPL than esketamine for a number of reasons. So I think this could potentially take over as the treatment of choice.

Yes. And maybe, Jason, if I can add, too. I think we talked about the broad treatment-resistant depression population in the U.S. and penetration within that with SPRAVATO or FDA-approved TRD treatment is so small. So I think absolutely, the low-hanging fruit here is those who are not getting the clinical effect from SPRAVATO or can't deal with the weekly visits or biweekly visits. But I think there is a much larger cohort potential that could potentially benefit from BPL as well within the TRD landscape.

Very helpful. Okay. Great. Moving on to another question. And Kevin, I'll oppose this to you. For BPL, can we go into the patient visit time to check in, the time to prepare for the therapeutic session, interactions with monitors? Just can you provide some insights into the patient experience before and after being dosed with BPL?

Yes, sure. And I think we've sort of touched on this already, but I would separate out maybe what we're doing in the trial, in particular, the core trial with what we're doing in the open label and what might ultimately be how we do this in clinical practice. So I mean, at the moment, we're taking -- we're doing certain things in the trial like collecting PK that aren't relevant and won't follow through into the clinic. So let's think about a patient who's coming in for maintenance therapy, so has had a number of doses before. What would that look like? We would expect typically kind of an intake so that there may be a check in the day before, maybe on the day where we're checking on the patient's mental state, any major life events. So generally just checking in before we dose the participants. Then there's the dosing itself and the monitoring thereafter that. And obviously, we're striving for a 2-hour discharge. And that's really where we're sort of aiming for, for that. And I think there would be -- in terms of sort of safety structures around that, clearly, the monitoring is going to be a key factor. And like SPRAVATO, blood pressure assessments and that sort of thing will be important as well. The safety data that we have to hand so far suggests that there aren't any other safety interventions that are going to be required for the majority. We know the blood pressure and that sort of thing is something that we need to monitor. And we certainly, as I mentioned, offered intervention with, say, benzodiazepines for anxiety or agitation. None of that was required in the Phase II. So I think those things are kind of in the back pocket, but it seems like the rate of their use will be low. And really, it's the quality of that monitoring and a brief intake that are going to be the most important. And I do expect that patients will become familiar with the dosing sort of logistics and time course over time. So that -- and we're trying to build that in even to our protocols to have sort of flexibility as we move into latter dosing, not to take it away entirely, but clearly, the first time you have this dose is going to be different to the fifth time you have this dose. So I think there are going to be -- we're going to see that evolve over time. But I want to hand this also off to the clinicians. You've dosed many of these patients for our trials and you have a much more hands-on sort of experiences. So I don't know if you have anything to add to that.

Well, I think that was going to be a very comprehensive answer then. Another question here. Ryan, I'm going to pose this one to you. Can you talk a little bit about our IP estate around BPL and how it may be able to prevent other branded 5-MeO based drugs from entering the market?

Absolutely happy to, Jason. I mean, I think as a preparatory point, we're here in service to our mission, which as I mentioned before, is to transform patient outcomes by developing rapid-acting, durable and convenient mental health treatments while executing in a way that drives meaningful value for all of our stakeholders. I'd also note that the depression and broader mental health markets are massive. In short, we don't view competition as a bad thing at all, and we root for other psychedelic developers. In a perfect world, the products reaching patients are those that can be predictably executed and which drive the best health outcomes as compared to an effective placebo. This is an area in particular where we believe that we and BPL-003 in particular, stand out. That said, we were founded on the traditional biotech belief that a strong patent estate is absolutely critical to ensure that we can effectively finance, thereby enabling us to achieve that mission. This was a key reason that I was brought on early in the company's existence. A strong patent estate comes from having the right strategy and executing well on it. We've discussed our approach and the fruits that my talented team has produced in the form of numerous issued and Orange Book listable U.S. patents. In my personal view, this is the type of point of question not asked enough of drug developers, particularly in the psychedelic sector. And while I'm not privy to any nonpublic information of those other developers and wouldn't comment on any specific third-party patent estates either way, I think the answers in some cases may well surprise you. Finally, I would note that as part of the comprehensive IP strategy we undertake here at AtaiBeckley, as noted previously, in terms of our Orange Book strategy as well as securing issued U.S. patents on alternative sites -- excuse me, salts, formulations, routes of administration and use in alternative indications is to ensure that we've got a strong foundation for commercialization and potential expansion while having multiple layers of defense, all of which we believe will make it very difficult for would-be competitors to design around our patent estate.

Wonderful. Thanks, Ryan. Appreciate that. We're coming up on the hour here. So I think we have one more question for Kavita and then a final question to our clinicians on the call. Vita, what pricing bands or kind of pricing considerations are we -- are you considering for 003 at this stage? Any kind of high-level commentary there would be helpful.

Sure. And it will definitely be high level. As we know at this stage, we're not at a position to provide any specific pricing guidance. What I will say and what I shared in the presentation earlier is when you look at kind of our closest proxy, at least in the market today, SPRAVATO, and you see the actual utilization in the real world of what the average patient is the dosing frequency often monthly at the higher dose, you're in a range based on our data of 60,000, maybe even well north of that. And this is WAC pricing. Pricing is complicated. There's a lot behind that. And so what I would say is if we truly deliver on this trifecta of benefit. So again, rapid acting, very durable compound that is convenient, this 2-hour window and convenient for patients and clinics, we believe that there is opportunity for premium pricing potential if that value is delivered. So I would just leave it at that at this point.

Perfect. All right. So I think one last question here, and I'll pose this to our clinicians on the call before handing this back to Srini to close. And just perhaps some final thoughts on the psychedelic field and what you're most excited about moving forward, just as some kind of parting thoughts before we close. I'd love to kind of hear those. So perhaps Dr. Wilkinson, you can start just because you're first on my screen here.

Yes. thanks. Well, I'm just excited that we have -- we're finally in a space where we have lots of different things with different mechanisms. For a long, long time in drug development, it was just me-too drugs. It was adding a methyl group to some SSRI or something like that. And we do owe a lot to the ketamine SPRAVATO story because that really I feel like opened up the field to really just thinking about, hey, one dose I mean a couple of times in this call, we've said SPRAVATO is not very long acting. But from a historical perspective, it is, right? You had a drug that has a 2-hour half-life and it couldn't keep people well for a week. That was a really kind of paradigm shifting reconceptualization. So I'm excited about the short acting and the potential for long durability.

Perhaps Dr. Feifel go next.

Yes. I mean I am just excited about practicing in a field where I feel I have really powerful weapons for maybe a lack of a better term to fight this monstrosity of mental illness, which is such a surge on society and it doesn't seem like it's going to be going away anytime soon with the nature of our society. And I actually went into psychiatry. One of the reasons I chose it was that I believe that it was on the precipice of a revolution. Neuroscience was advancing so rapidly. And I thought it's going to translate into great changes. And not many students were choosing psychiatry. I actually posted a paper about student attitudes because we couldn't fill our residency slots and about a decade ago, a little over a decade ago, things were so gloomy because companies were pulling out of R&D. In fact, there was a New York Times column by psychiatrists who talked about the innovation crisis in psychiatry. It was a really kind of gloomy time. And I was still -- I said I'm a decade into my career, and I'm still writing prescriptions for the same -- essentially the same drugs that my mentors were writing when they were residents. They got a little fancier and so forth, but they were essentially the same mechanism of action. I was thought, wow, this is -- I may have miscalculated here. And thankfully, look, here we are. I described this as sort of the Cambrian explosion of new treatments where we've got an embarrassment of riches of all these new and they are they are revolutionary. If you want -- if I had to precipitate down to what am I excited about, sitting across the desk from a patient that I know I've got something that will change their life where I did not feel that for. I almost felt like I was just trying to string them along and say, well, what if we just change the dose here, we had this drug, we had this drug, but I wasn't really convinced that I was really doing something dramatically different. And now I just feel like I've got stuff. I've got -- and what's coming down the road, I'm going to really have some good stuff.

Dr. Hendricks?

There's a lot I can say about this. But let me just start by saying my interest before I knew psychedelics existed was in a concept known as quantum change and that captures this idea that sometimes people do change rather suddenly and dramatically and this change is durable. But it happens or happened so infrequently, it was fair to say that scientists didn't really understand that process. So we have fictionalized versions of it in the case of, say, Ebenezer Scrooge. I was always fascinated by the story that sometimes people can change dramatically and for good. And when I came across the literature on psychedelics, my first thought was, well, my goodness, we can actually schedule quantum change for a time and place. Now I recognize that not everybody has that experience, right? And like any intervention ever, not everybody will respond. But I think prior to psychedelics, usually in a clinical trial, if we had a successful intervention, that intervention would, in fact, have ultimately failed less than the placebo, but was still not successful for most participants. That's demoralizing for the clinician when we know that even our best treatments won't work for most. I think with psychedelics, the tide is turning. And as David mentioned, we're at this place now where we might be able to offer treatments that work for most people. Not only that, but they speak to a mechanism of action that can cut across diagnoses. And that's likely because potentially, these interventions are getting at the core of the mental health condition rather than only addressing the symptoms. And personally, I think one thing that makes psychedelics quite unique is that they get at deeply held personal values and how we form meaning in life and allow people some clarification of these values and perhaps alignment of their behavior with those deeply held personal values, which is a good thing. So I'm quite excited. I also do want to say again that I think in the case of BPL, we have a very unique psychedelic that is not just, say, psilocybin in a shorter-acting form. I think it has a number of unique properties that could make it especially amenable to a wide range of mental health conditions and in a way that is scalable to the clinic workflow. So as this conversation has gone on, I've become more enthusiastic as we're talking about these things out loud, but it's a really exciting time to be involved in this space because I think we're on the precipice of offering a treatment that could really work for the majority of people and that the majority of people can access.

Wonderful. Thank you very much, and a special thanks to Dr. Hendricks, Dr. Wilkinson, Dr. Feifel for joining us today. Insights were just incredibly valuable, meaningful, impactful. So really appreciate you joining. And with that, Srini, I think I'll pass this back to you for some closing thoughts before we end today.

Yes. So let me start by actually reiterating what you just said, Jason, thank you so much, Dr. Feifel, Dr. Hendricks and Dr. Wilkinson, just for your time, which was significant, your enthusiasm and also for all those insights. I want to thank the audience as well for their interest and all the great questions that we received over the course of the call. Thank you to the team for making this webinar possible, obviously, and all the hard work it took to get the company to this place. 2025 was transformative for the company. A lot of things happened, a lot of great things happen. 2026 promises to be so as well. So we've got -- we're getting this Phase III program up off the ground. We're awaiting the data for VLS-01. It's also worth mentioning, it's going to be an exciting time for the space. We've got some Phase III readouts will be coming up, have had some, and we'll have others as well. So it's really important for the patients. So stay tuned, and we look forward to continuing the discussion with all of you.