Good day, and welcome to the top-line results from the phase II ZEPHYR study of ML-007C-MA in schizophrenia. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question- and- answer session. Instructions will be given at that time. As a reminder, this call may be recorded. I would like to turn the call over to Chris Kroeger, Co-Founder and Chief Executive Officer of MapLight Therapeutics. Please go ahead. Good morning, everyone, and thank you for joining us. I am Chris Kroeger, Co-Founder and Chief Executive Officer of MapLight Therapeutics. Today, we are going to walk through top-line data from our phase II ZEPHYR trial evaluating ML-007C-MA in schizophrenia. I am joined by our Chief Medical Officer, Dr. Erin Foff, who will take you through the study design and results in detail. Before we get started, I would like to remind everyone that this presentation contains forward-looking statements that are subject to risks and uncertainties as described in our risk factors in our filings with the SEC. Let me quickly walk you through today's agenda. I will start with an overview of the ZEPHYR results, followed by a brief outline of the significant remaining unmet need in the treatment of schizophrenia and the ways in which we believe the data from the ZEPHYR study address that need. Dr. Foff will then walk through the study design and describe the efficacy and safety results in detail. After that, I will come back to discuss the ZEPHYR results in the context of the competitive landscape and outline our future development considerations, followed by some closing remarks. We will leave time at the end for Q&A. We are very excited to report that ZEPHYR, which was designed as a pivotal trial intended to support registration, met its primary endpoint, demonstrating a substantial treatment effect that was supported by concordant improvements across multiple secondary efficacy measures. Importantly, on top of efficacy on PANSS, we also observed a robust and clinically meaningful improvement in cognitive performance on a pre-specified secondary endpoint. Something we believe could support the differentiated clinical profile, not only in schizophrenia, but also in our broader development programs in both Alzheimer's disease psychosis and Alzheimer's disease dementia. ML-007C-MA showed a favorable safety and tolerability profile with low rates of all-cause discontinuations and low rates of moderate GI side effects. We believe this is a profile that will allow patients to take the drug and stay on therapy. ML-007 was designed for ease of use. There is no fasting requirement and only a short one-dose titration. Aspects that we believe will support translatability of these results into real-world use. Taken together, we believe this data supports proceeding to an additional pivotal study to support registration, and planning and site identification are already underway ahead of our end-of-phase II interactions with the FDA. On slide five, I want to spend a moment on why these promising results matter. Unmet need in schizophrenia remains very high. It affects more than 20 million people globally, and patients remain underserved by current standard of care antipsychotics. Nearly a third show no meaningful response to treatment, approximately half experience an inadequate response, and a significant majority discontinue oral therapies within 18 months, often due to lack of efficacy or burdensome side effects like extrapyramidal symptoms or weight gain. As the first new mechanism approved in decades, Cobenfy represents an important advancement in the treatment of schizophrenia. However, significant obstacles to effective therapy remain. Cognition is one of the key symptom domains in schizophrenia, and while Cobenfy has shown some suggestion of cognitive improvement in its clinical studies, the potential for cognitive benefit remains unproven as those signals came from post hoc or exploratory pooled analyses. Additionally, many patients do not reach or remain at Cobenfy's target dose due to significant side effects, primarily GI side effects. If patients are unable to take a drug, they're unable to benefit from it. Tolerability is significantly worse in the real world relative to controlled clinical trials. We'll discuss why that may be later in the presentation. Importantly, we think the attributes of ML-007 may avoid these liabilities. Moving to slide six, we believe the data from ZEPHYR demonstrate meaningful differentiation and address the key challenges that saddle existing muscarinics. At the 210/3 mg BID dose, we met our primary endpoint on the PANSS total score with an effect size of 0.37. Well within range with currently approved therapies used to treat schizophrenia. In our pre-specified completer analysis, where modeled assumptions for missing data are not utilized, the effect size was 0.5. We also saw separation on multiple concordant secondary endpoints, including Clinician Global Impression Severity and positive symptoms. This dose also demonstrated a robust improvement in cognitive performance. In participants with baseline cognitive impairment, we saw substantial improvement versus placebo on our pre-specified cognitive composite score with an effect size of 0.51. We looked at whether that cognitive change tracked with PANSS improvements and did not find a significant correlation, indicating the effect was not likely secondary to reduced psychotic symptoms. We believe this cognitive signal, consistent with ML-007's strong agonism at M1, is a critical differentiating feature, not only for schizophrenia, but also for the treatment of ADP and AD dementia. We believe the combination of a meaningful effect on PANSS, along with a meaningful effect on cognitive performance represents a powerful, comprehensive overall efficacy profile that is unique. When we set out to develop ML-007, we focused extensively on a precise PK match of the procholinergic and anticholinergic components of our drug candidate in order to minimize significant peripheral side effects while delivering efficacious exposures, and we believe the safety and tolerability profile in ZEPHYR rewarded those efforts. ML-007C-MA was generally well-tolerated. There were no serious or drug-related severe adverse events. Discontinuation across the active arms was low at 19.9%, nearly half the rate demonstrated for Cobenfy in EMERGENT-3. Only two patients discontinued for GI adverse events in the BID arm, and only four participants reduced dose due to adverse events. The rates of moderate GI side effects were low, and there was no hepatic, metabolic, weight gain, or movement-related signal, and no urinary retention. Again, there was no fasting requirements or complex titration, which we believe will reduce barriers to adherence outside the controlled trial setting. With that, I'll hand it over to Erin to walk through the study design and results in more detail. Thank you, Chris. Good morning, everyone. I'll briefly take you through the ZEPHYR study design, then walk through the efficacy and safety results in more detail. Moving to slide eight, ZEPHYR was designed and sized to serve as a registrational study, as Chris mentioned. Our engagements with the FDA thus far have signaled that intention. The study was quite large. We operated at 25 U.S. sites, and we randomized 307 participants equally to placebo, the twice daily, and the once daily active arm. Dosing employed a single-dose titration to both target doses, and participants had the option to dose reduce between weeks one and three based on tolerability. The primary endpoint was changed from baseline in the PANSS total score at week five. The key secondary endpoints are listed here in the order in which they appeared in the statistical hierarchy. I'll come back to that concept later. As Chris has mentioned, we also had a pre-specified secondary endpoint of change from baseline in the cognitive composite score of the Cogstate battery in the subgroup of participants who had cognitive impairment at baseline. Before I get to the study results, I want to take a brief look at baseline characteristics on slide nine. The three arms were generally well-balanced in the study. Mean age was 40 - 42 across the arms, and most participants were male and Black or African American, which is similar to historical inpatient studies. The baseline PANSS total score averaged 96 - 97 across the arms. I won't dwell on the slide, just wanted to establish that we started from a population that was generally well-matched in baseline characteristics. On slide 10, we'll turn to the primary endpoint. As Chris has already mentioned, ZEPHYR met its goal of demonstrating efficacy of active treatment over placebo. Both doses yielded numerical separation beginning as early as week one. The 210/3 mg BID dose showed a significant reduction in the PANSS total score versus placebo beginning at week three and separating further at week five. This is with multiplicity adjustment. In the modified intent-to-treat population, which is the standard population analyzed in schizophrenia trials, the LS-mean change from baseline was 11.7 points for the BID dosing arm versus 7.2 for placebo, a difference of 4.5 points and an effect size of 0.37 with a statistically significant p- value. Though it separated numerically, the effect in the 336 mg once daily arm did not reach statistical significance on the primary endpoint. Notably, it did separate on several other endpoints, including the CGI-S, the PANSS positive Marder factor, and the PANSS positive subscale score. Importantly, this is our lower dose. Its total daily exposure is proportionally lower than the 426 mg associated with BID dosing. I'll also note that the 210/3 mg BID dose is the same dose currently being evaluated in our ongoing VISTA study in Alzheimer's disease psychosis. Before I move on, I just want to point out the very low placebo response rate in this study. We made every effort to control placebo response in ZEPHYR and throughout trial conduct. We've detailed that approach on many occasions. It's clear that those efforts worked very well across this large study. You can see the tight error bars on measures demonstrated here, and you'll see that again on several other slides. This has been a challenge in many studies in the space, and we think that our aggressive efforts, including repeated placebo response training, in-house site monitoring responsibilities, and strict data quality oversight, produced a placebo response rate that's rarely observed in trials this size, and it indicates that we can operationalize this control in future studies. As shown on slide 11, we also conducted a pre-specified completer analysis. This excludes assumptions about missing data from the MMRM model and instead relies solely on observed data across the full assessment period. This is similar to analyses done with other agents to treat schizophrenia, some of which we'll show you later. In that analysis, the 210/3 mg BID effect size was larger at 0.5, a six point difference versus placebo. That larger difference was driven by additional improvement in the BID arm itself and not by a change in the placebo response of completers. On slide 12, on the Clinical Global Impression of Disease Severity, we saw clinically meaningful and statistically significant multiplicity-adjusted improvement versus placebo at week five with a very robust effect size of 0.48. The reason I mention the multiplicity adjustment here is that this did hit in the hierarchy of the statistical plan, and the CGI-S has the potential to be in the label. Several other antipsychotics do have the Clinical Global Impression of Severity in the label, but that does require statistical separation in the hierarchy, which has been demonstrated. Numerical separation, again, begins early, and you can see that that continues throughout the treatment period. On slide 13, I want to focus on PANSS positive symptoms. Our key secondary endpoint was changed from baseline in the positive Marder factor score at week five. We similarly pre-specified a look at the positive subscale score, which was the key secondary endpoint in the EMERGENT trial. We again see early and continued separation from placebo, significant by both measures, with an even greater effect with the positive subscale. Here, the effect size was 0.56. As a reminder, the effect size observed on this endpoint in EMERGENT-2 was 0.59. Shown on slide 14, is an analysis that we were really eager to see and we were particularly encouraged by. This is the pre-specified cognitive composite score of the Cogstate battery. In the participants with cognitive impairment at baseline, the twice-daily dosing arm demonstrated a robust improvement versus placebo with an effect size of 0.51 and a p- value of 0.041. We looked closely at whether this cognitive improvement was simply tracking with PANSS improvement in this exact population, we did not see a significant relationship between the two. As you can see, the r- values are low and the p- values are non-significant with really shallow slopes. This apparent independence matters because it suggests that the cognitive signal is not simply a downstream effect of reduced psychotic symptoms. On slide 15, I want to spend a moment on why we think this cognitive finding matters beyond ZEPHYR itself. It was observed on a pre-specified secondary endpoint, as was mentioned, it appears independent of PANSS change. It's also consistent with the established role of M1 receptor activation in learning and memory, the strong M1 agonism of ML-007C-MA, and the effect that we observed on cognition in preclinical animals. Together, this provides a compelling mechanistic rationale for this effect. It also matters because cognitive impairment is estimated to affect more than 80% of patients with schizophrenia, it's a major determinant of long-term functional outcome. Despite decades of research, no therapy has been approved to treat cognitive impairment in schizophrenia, which speaks both to the unmet need and to the difficulty of demonstrating meaningful cognitive benefit. Sedation and dopamine blockade from many standard-of-care antipsychotics may, if anything, worsen cognition. Importantly, to have a labeled indication for cognition in this space, one has to conduct a specific study in patients with baseline controlled psychotic symptoms. However, we do believe that this will be meaningful to clinicians, we may decide to pursue such an indication in the future. This positive effect on cognition also increases our confidence that this biology may translate across neuropsychiatric populations, including in Alzheimer's disease psychosis, where we know off-label antipsychotic use has been associated with accelerated cognitive decline. Thus, it's particularly relevant to VISTA, our ongoing study evaluating ML-007C-MA in Alzheimer's disease psychosis, and in any study with ML-007C-MA assessing cognition in AD. As noted, VISTA utilizes the same BID dose that demonstrated cognitive benefit in ZEPHYR, we'd expect to use this same dose in additional Alzheimer's disease indications. Stepping back, slide 16 summarizes the effect of twice-daily dosing across the endpoints that I've just walked through. I think this is a really important slide to put into context all of the key secondary and secondary endpoints that we've detailed here, and some that we haven't yet talked about. All of these measures favor ML-007C-MA active treatment. In fact, the only one that doesn't reach statistical significance is the PANSS Marder negative factor. I haven't yet talked about the CGIC and the PGIC, but both here did also demonstrate improvement with active treatment with effect sizes of 0.47 and 0.38, these represent both the clinician global impression of change and also the patient global impression of change. Notably, we also assessed two additional important outcome measures. First, participants on ML-007C-MA twice daily were 2.4 x more likely to demonstrate a meaningful 30% response on the PANSS total score by week five, a threshold commonly employed to represent clinical meaningfulness. We also assessed how likely participants were to have improved enough to be prepared to leave the hospital, which could have meaningful economic and quality of life ramifications. Those on active treatment were 2.8 x more likely to be considered ready for discharge from the inpatient setting. Turning to safety and tolerability on slide 17, which was a key objective for this program from the outset, ML-007C-MA was generally well-tolerated across both doses. Adverse events were primarily procholinergic in nature and mostly mild. There were no serious or drug-related severe treatment-emergent adverse events with either dose. The one severe TEAE observed, a case of pneumonia, was assessed as unrelated to study drug. The single serious adverse event of worsened schizophrenia occurred in the placebo arm, which helps confirm that we enrolled the right population. We'll spend more time on the next slide on the details in the second section here. In general, the GI profile indicated low rates of moderate events and low rates of GI-related discontinuations. We'll discuss later why we think that will translate into the real world. As anticipated, given our slightly more procholinergic profile, we did not see a signal of urinary retention and had only a single moderate urinary event of urinary tract infection in each of the active and placebo arms. As expected, we saw no metabolic, hepatic, or EPS motor signal with mean weight, glucose, lipid, liver enzyme, and movement-related parameters comparable to placebo. Heart rate increases were small and consistent with those observed and noted in the fesoterodine label. We did not see evidence of significant blood pressure elevation. Moving to slide 18. As noted by Chris, all-cause discontinuation in the actively treated participants in this study was quite low, 19.9%. I do want to mention that we interrogated each of these discontinuations extensively to ensure we were not missing discontinuations due to indolent adverse events. Discontinuation due to a treatment EMERGENT adverse event was 7.1% in the twice-daily dosing arm. Discontinuation specifically due to a GI TEAE occurred in only two participants. Dose reductions were also infrequently employed. Only four participants in the BID dosing arm versus two in placebo reduced dose due to TEAEs, and inability to reach the target dose occurred in only 1% of participants. This single participant who failed to reach the target dose was actually removed from the study following titration due to abnormalities in pre-dose baseline labs that were not treatment emergent. The large majority of TEAEs were mild, with only the single unrelated severe TEAE I've already mentioned and no serious adverse events with active treatment. Looking at the specific GI events occurring in more than 2% of the active arm and occurring at a rate greater than that of placebo, all were mild to moderate in severity, and most were mild. Anticholinergic GI events such as dyspepsia, constipation, and GERD were less frequent than procholinergic events, but similarly mostly mild. To give that context, mild was defined as those adverse events that were easily tolerated with no significant limitations in activities such as eating and exercising, and moderate events were those that caused discomfort significant enough to limit normal activities and potentially require intervention. We did not have a blood pressure signal. Only a single participant had an adverse event of hypertension that was considered unrelated. They had entered the study with uncontrolled hypertension, and the incidence of orthostasis was similar in the placebo and active arms. On slide 19, I want to spend a moment on published data to provide context for tolerability because we think it's a really meaningful part of the story. Data from the pivotal EMERGENT-2 and EMERGENT-3 studies for the only approved class member, Cobenfy, show all-cause discontinuation ranging from 25%-37%. Discontinuations due to adverse events were similar at 7.1% and 6.4%, and discontinuations due to GI treatment-EMERGENT adverse events were 3.2%, generally higher than what we observed in ZEPHYR. Critically, in both EMERGENT studies, 7%-8% of participants had severe adverse events, which of course are quite clinically meaningful, and overall rates of moderate to severe events were higher, 34%-36%, than the 26% observed in our trial, despite similar study sizes and site numbers. Importantly, we don't believe that the inpatient experience with Cobenfy has particularly matched the outpatient experience. In their open label extension studies, the discontinuation rates were 51%-78%, and early data on prescriptions indicate that at one year, over 80% of those prescribed drug were no longer taking it. A separately published real-world analysis of 90 patients suggests GI tolerability challenges with Cobenfy may be more pronounced outside the controlled inpatient trial setting. In that analysis, nausea rates were more than three times those observed in patients, and vomiting rates were more than two times those in the pivotal trials. Over 80% of patients did not reach the highest dose, and roughly 25% remained on the titration dose. Importantly, 55% of patients required medication to manage GI symptoms, many of them prophylactically, and the majority did not achieve full relief with medication for these GI side effects. Reasons for the disconnect here are not really fully understood. It's plausible to us that it's related to exposure differences secondary to the fasted state. In the inpatient setting, the requirement for fasting can be closely adhered to. However, in an outpatient setting where patients may not be able to fully comply with the requirement to fast one hour before or two hours following dosing, the impact on exposure may complicate tolerability. When taken with food, trospium levels plummet by greater than 85%, and xanomeline exposures tend to increase. This may exacerbate the mismatch between the two components, leading to impaired tolerability. Conversely, ML-007C-MA is recommended to be taken with food because it is a gastroretentive pill. But the ratio of the components remains within target range in the fasted state, suggesting that tolerability in the inpatient setting will not be altered significantly by outpatient adherence to food requirements. With that, I'm going to turn it back to Chris to talk about the context of these results and what's next for the program. Thanks, Erin. Moving to slide 21, in order to understand how ML-007 could fit into the current treatment landscape, it's helpful to view it in the context of currently approved and commonly used medications in the space. This chart shows standardized effect sizes, Cohen's d, for PANSS total score across approved antipsychotics, alongside our own modified intent-to-treat and completer results for the 210/3 mg BID dose. These figures come from different studies, different populations, different points in time, and they're not head-to-head comparisons. But with those caveats, the use of effect sizes does allow for some interpretation of relative efficacy results. With that framing, our effect size of 0.37 falls within the range reported for currently approved antipsychotics, which has historically spanned roughly 0.26-0.56. As you can see, many highly commercially successful drugs were approved with very similar effect sizes. Importantly, our completer effect size of 0.5 is at the higher end of the range among those with published completer analyses, shown here in yellow. Data from the completer analysis of EMERGENT-2 and 3 suggests the effect size of 0.48 and 0.63, indicating that our effect is comparable when missing data assumptions are not utilized. Notably, we believe prescribing physicians are focused on whether a drug is approved and works and is tolerable enough to be taken by their patients, and they are not terribly focused on effect size or PANSS deltas. Consequently, we do not believe the effect sizes from clinical studies have meaningful impact on commercial uptake. On slide 22, I want to walk through potential differentiation for ML-007C-MA within the competitive landscape. Again, I stress that these are qualitative assessments based on publicly available information and our own internal analysis and not head-to-head data. And that comparisons across different study designs warrants appropriate caution. With that said, ML-007C-MA and Cobenfy share a similar mechanism, an M1/M4 agonist combined with a peripheral antagonist, and both, along with atypical antipsychotics, have demonstrated substantial efficacy results in large randomized controlled trials. On cognition, we observed robust improvement on a pre-specified secondary endpoint. While xanomeline demonstrated promise in the sphere, as mentioned, these analyses have been post-hoc or from exploratory pooled datasets, and the magnitude of effects has not yet been fully assessed. The M4-only approaches, direclidine and emraclidine, lack M1 activity and thus are not expected to confer a cognitive benefit, and standard of care antipsychotics may contribute to cognitive impairment secondary to sedative and dopaminergic effects. As we've discussed, our tolerability profile reflects significantly lower rates of clinically meaningful side effects. And since ML-007 has no fasting requirement and uses a simple one-dose titration, we believe this tolerability profile will translate to real-world use. It's critically important in the schizophrenia population since patients can only benefit from drugs they are actually able to tolerate. Lastly, like Cobenfy, we are advancing BID dosing into subsequent studies, including in ADP, where Cobenfy is dosed three times a day. However, we continue to explore an alternative once-daily dosing frequency. Moving to slide 23. Often there's concern following a phase II data readout that those phase II results may not translate to a larger registrational study. ZEPHYR was designed and sized from the outset to support registration and is in fact larger than both EMERGENT-2 and EMERGENT-3, the two phase III studies for Cobenfy. Following our end-of-phase II meeting with FDA, we plan to run two additional confirmatory pivotal studies. ZEPHYR-2 will essentially replicate ZEPHYR, evaluating the 210/3 mg BID arm versus placebo in a similarly sized study at U.S. sites. Together with ZEPHYR, we intend for it to support our initial NDA submission. ZEPHYR-3 will again evaluate the 210/3 mg BID dose with the potential to evaluate alternative dosing regimens, including a potential alternative once-daily regimen. Our exposure response analysis is ongoing, but preliminary data suggests that overall exposures in both arms were meaningfully lower than exposures in our phase I studies. The once-a-day arm did separate numerically on PANSS and delivered separation from placebo on several of the secondary endpoints, so we continue to believe that there is a path forward. Once we've analyzed the full data set and have better insight into the exposure response, we may elect to explore alternative once-daily options in ZEPHYR-3. Separately, our VISTA study is ongoing in Alzheimer's disease psychosis and is also designed to support registration. It remains on track with top-line results expected in the second half of 2027. We're encouraged by the pre-specified cognitive signal we saw in ZEPHYR, particularly because the VISTA study employs the same BID dosing regimen that achieved the safety and efficacy results in this trial. Beyond ADP, we're also evaluating the drug candidate's potential in additional indications, including mild to moderate Alzheimer's disease, for which we also believe a positive signal bodes well. In summary, ZEPHYR met the primary endpoint on PANSS total score with an even stronger effect in our completer analysis and hit on multiple concordant secondary endpoints. Importantly, ML-007 demonstrated a robust effect on our pre-specified cognition endpoint that appears independent of its antipsychotic effect. Our precision matching of the two components of the drug candidate produce a very attractive safety and tolerability profile that we believe will translate well into real-world use. Taken together, we believe this data supports advancing ML-007 into a confirmatory pivotal study and continuing our investments in indication expansion, leveraging the cognitive signal we observed. Before we move to Q&A, I want to briefly zoom out on our broader pipeline, which we believe reflects the versatility of our circuit-based discovery platform. Beyond ML-007C-MA in schizophrenia and Alzheimer's disease psychosis, we're advancing ML-004, a 5-HT1B/1D agonist to treat irritability in autism spectrum disorder. Following our recent disclosure of the encouraging results from our IRIS study, we plan to engage the FDA in an end-of-phase II meeting. ML-009 is a GPR52 Positive Allosteric Modulator we're developing for hyperactivity and impulsivity, and is expected to complete IND-enabling studies in 2027. ML-055 is a next-generation M1/M4 agonist for neuropsychiatric disorders, and it's on track for preclinical candidate nomination in 2026. Lastly, ML-021 is an M4 antagonist for Parkinson's disease, which we expect to reach candidate selection in 2027. With that, we'll open the line for questions. Operator, please go ahead. Thank you. If you'd like to ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Marc Goodman with Leerink. Your line is open. Yes, good morning, Chris. Can you talk about the lower drug exposures that you saw and just what you thought happened there and how you're thinking about that? Then also, can you comment on the negative symptoms data? There didn't seem to be anything there. I'm just curious why you thought that was the case. Thank you. Thanks, Marc. Appreciate the question. With respect to our overall exposures, again, the exposure response analysis is ongoing, so it's very preliminary. We did see lower exposures in both arms of the study compared to what we saw in our phase I study. We don't really have a complete explanation as to why that is. Our drug is, the pill is a gastroretentive pill, so we're looking at a number of things that may affect gastric retention, like proximity of dosing to the meal, and also time of day of dosing, because GI transit can slow in the evening. Again, as we get that full data set and are able to perform the full analysis, then we'll be able to make some clearer conclusions about why the exposure was a little bit lower. Maybe I'll ask Erin to answer the question on the negative symptoms. Sure. What we didn't really talk about deeply was that the negative symptoms did move in the right direction. We did have numerical separation. We didn't hit statistical separation. Those are historically some of the hardest symptoms to move in a short study like this, five weeks. Actually, in our study, the LS mean difference in the BID arm was actually greater than was seen in one of the two EMERGENT studies. As you know, those were differential responses across the Cobenfy program. These are distinct cluster symptoms. They change independently from positive and negative symptoms. We'll need to dig in a bit deeper, like Chris said, even exposure response for the efficacy in the negative domain to understand that data more deeply. Yeah. Thanks. Sure. Thank you. Our next question comes from Paul Matteis with Stifel. Your line is open. Great. Good morning. Thanks so much for taking my questions. I appreciate it. On this point around exposure and predicted exposure, I guess, what's your confidence level that the exposure levels you're predicting for ADP will be correct? How would you think about the risk that just other factors or concomitant medications in this population could potentially confound that? Then as it relates to a subsequent schizophrenia study, based on this effect size here, how might you think about powering that study conservatively? Are you thinking that that's likely a two-arm study at this point? Thanks so much. Yeah. Thanks, Paul. Appreciate the question. Yeah. With respect to exposures in the VISTA study, I think we do expect the exposures are likely to be similar. We haven't seen any exposure differences between elderly and younger folks in our phase I studies. I don't think we're expecting anything to be different there. Again, I think we believe the effects that we've seen in this study actually are quite clinically meaningful and robust. We expect that'll carry through in the VISTA study, and importantly, having hit on cognition, we think that bodes quite well for that study. Remind me, what was the second part of the question? It was about powering for the next schizophrenia study. Right. The design of that study is still ongoing, we don't have any final numbers of that. Again, I think it'll be of a similar size to this study. It will be a two-arm study. Given this study was powered for an effect size of 0.5, we hit an effect size slightly lower than that. Given that it'll only be a two-arm study, I still think it'll be generally in the same ballpark in terms of sizing. Okay. Thanks, Chris. Thank you. Our next question comes from Andrew Tsai with Jefferies. Your line is open. Thanks. Good morning. Appreciate all the analyses for a successful schizophrenia study. Given this kind of data set you've generated now, can you maybe summarize all the various pieces of evidence that gives you the confidence 007 can be superior to Cobenfy on efficacy in ADP, especially in the context in the hypothetical scenario where Cobenfy failed, why could you still be better? Secondly, should we expect an outcome from the end-of-phase II meeting sometime second half 2026, or could it spill into 2027? Thanks. Yeah. On the second question, we can't really answer that at this time. Once we've had our engagement with FDA and know when that's going to happen, we'll guide to that a little bit further down the line. With respect to the first question, I'll start, and Erin, feel free to jump in. I think when we look at the overall efficacy of 007, it's really the totality of the package that we see that gives us real confidence and is really the basis for assessing whether we think the drug is working in this patient population. That's the combination of efficacy on psychosis, which is the PANSS score, as well as all the other key secondary and secondary endpoints, all of which move in the same direction and all of which move in a meaningful direction. That combined with a meaningful and statistically significant improvement in cognition on a pre-specified endpoint, combined with tolerability. Patients can't benefit from a drug that they're not able to take and remain on. That tolerability piece is so critically important. If you can have a better-tolerated drug, which we think we have demonstrated here, patients will be able to remain on the drug, take the drug consistently, and that's really kind of the key element that physicians and prescribers care about. I think in terms of the robustness of the effect, if we look across all of the key secondary symptoms, you can see we had a strong effect on the PANSS score. That is a single data point, an important data point, the one that's used for approval in the space. We hit on that, with an effect size right in the range of existing atypical antipsychotics. We look at the completer analysis, obviously, it's quite strong and well within the range of Cobenfy. Beyond that, the other important secondaries, like the Clinical Global Impression of Severity, had a very strong effect size. The clinician's impression of how well the patient is doing had a strong effect and well within the range of Cobenfy. The positive symptom score had a very strong effect, essentially equal to that demonstrated by Cobenfy. Lastly, the 30% responder rate. The odds ratio there, again, was in line with that for Cobenfy. All of those things really give us a lot of confidence that the total efficacy picture here is quite strong. Maybe I'll just jump in and sort of talk a little bit about how we think this translates into ADP and then specifically, I think, Andrew, your question about what if the ADEPT studies don't read out positively. Specifically as it pertains to the ADP population, when we look at the subscale scores that moved the most in this study, they are the ones that are most translatable to the NPI-C that's being assessed in the ADP trial. That's number one. I think that gives us a lot of confidence that the needle will be moved on those meaningful psychosis domains in the Alzheimer's disease psychosis population. Specifically regarding why would we still believe we might move if ADEPT doesn't hit, there are significant design differences between our ADP trial and the ADEPT trials. Setting aside the relapse prevention trial design, which is a completely different design. In the acute studies, the meaningful differences there that we think may impact possible positive study readout are the fact that the ADEPT studies, the acute studies, are longer in duration. They are 12-14-week studies. We are mindful of the fact that in natural history studies in Alzheimer's disease psychosis, there's some waxing and waning with some improvement right around that time point. It's a difficult time point to assess differences from placebo. Conversely, that's really a necessary part of their design because there is a five-week titration to target dose there. We can stick with a really, truly acute study. We have a seven-week study because our titration is only a week in the VISTA trial. We think that that's a better time point to assess change for acute psychosis. Lastly, everybody in the VISTA study will be titrated to target dose. They can drop down if they need to based on tolerability, but there really is only the target dose and that single drop-down dose, which we believe will confer efficacy as well. In the ADEPT studies, there are multiple steps in the titration. Patients can stay on the lower doses, and it's really only the higher dose that has known efficacy in the population based on the Lilly study. We still have reason to believe if ADEPT does not read out, that VISTA will demonstrate efficacy with the same dose that was used here to demonstrate efficacy. Thanks very much. Very clear. Thank you. Thank you. Our next question comes from Sean Laaman with Morgan Stanley. Your line is open. Hi, this is Mike on for Sean. Thank you for taking our questions. In the context of the cognitive improvement you've observed with ML-007 on Cogstate, do you think the weaker absolute PANSS scores in ZEPHYR relative to EMERGENT and direclidine, does that support the view that M1 is favoring cognition, M4 agonism is for psychosis? Thanks. We have a follow-up. Yeah. Thanks, Mike. I can start, Erin can follow up. I would reiterate that while our PANSS score effect size may be a little bit smaller than the effect size demonstrated for Cobenfy, these are different studies at different points in time, different populations, et cetera. They're not head-to-head comparisons. It's not easy to do those cross-trial comparisons. That said, we've got a strong effect size, and that's supported by multiple other measures that I just mentioned, including, importantly, that 30% responder rate, which more than a third of the patients hit that 30% response rate. I think all important in telling elements of the efficacy picture. Clearly we hit on cognition, and we hit on it robustly, and I do think that's a consequence of M1 activity. We have a stronger M1 agonist that is Cobenfy, based on both in vitro and in vivo preclinical animal model data where we showed very significant improvement in cognition superior to Cobenfy. We do believe that's part of the profile. We also have a strong M4 agonist. That's why we think we're able to deliver across the full suite of symptoms. Thank you. That's very helpful. Maybe just a follow-up question on the dose response. With the lower 210 /3 mg BID arm outperforming the high dose once daily, I guess it's too early to say whether it's an actual inverted dose response, are there any data on Cmax or AUC that would help to explain the incrementally lower efficacy observed at the high dose? Thanks for the opportunity to clarify. It is very much not an inverse dose response. The 210 /3 mg BID dose has a greater AUC than the 330 once-a-day dose because 330 is once a day. 330 has a higher Cmax, we believe efficacy is driven by AUC, whereas adverse events are largely driven by Cmax. It is, in fact, dose proportional in terms of the effect that we saw. Thank you. Very helpful. Thank you. Our next question comes from François Brisebois with LifeSci Capital. Your line is open. Hi. Thanks for taking the question. Just a couple ones. Sorry if this was mentioned. I was just wondering if you can touch on the efficacy side, a little bit of that delta with the completers and how that kind of works there. Then just maybe touch on the efficacy side of a potential functional unblinding in this trial. Then on the tolerability front, if you can just kind of help us understand the differences in severity here seen versus Cobenfy and why it's possible. You mentioned fasting requirements. Maybe it's just possible to think that this trial was a lot more like real-world setting than a Cobenfy type trial. Thank you. Erin, do you want to respond to that one? Sure. In terms of the completer analysis, maybe I'll back up and just talk about the standard analysis first to put that in context. In a standard mITT, that's the population everybody uses in a schizophrenia trial. When participants leave the trial early for any reason, then the MMRM model has to make assumptions about the course of that particular patient's response at five weeks, which is what the primary endpoint is. It models missing data. A completer analysis, on the other hand, doesn't need to do that. Instead, it looks only at observed data at week five and says, in the participants in whom you have all of the actual data accumulated, what is the response? This can really go either way for you. Completer analysis do not automatically make things better or worse. They just tell the story of the people for whom you have all of the observed data. When we look, for example, at the EMERGENT-2 and 3 trials, the completer analyses there went actually in opposite directions for those two trials. In one of the two trials, the completer analysis slightly bumped up the effect size, and in the other, it bumped it down. That puts our completer analysis really smack dab in the middle with an absolute delta PANSS that is right in line with them. That's helpful, and it's helpful for a clinician because you can say, if your patient is taking this drug four or five weeks, this is likely to be their response. I think your second question was about functional unblinding. When we powered this study, we actually thought that because coming in, we believed we'd have a better tolerability profile, which is now actually borne out to be the case, that it's possible that we would have less functional unblinding in the trial, which is good for the science, but can certainly impact the observed changes in scores. Essentially, people cannot unsee projectile vomiting or severe constipation or urinary retention, and it has the potential to impact their scoring. We do believe there's a possibility that because our rates of moderate, severe, and worse AEs were low, that it's likely that functional unblinding was less of an issue for us than it may have been in other trials. In terms of translatability into the real world, I think you're hitting on exactly what we think to be the case. We asked in the trial that people take the drug with food, but it wasn't an absolute requirement. If people weren't hungry, they didn't have to eat. They weren't forced to eat. There was no absolute or minimum requirement on the amount of food that had to be taken. As we mentioned during the presentation, what we do know is that if our drug is gastroretentive, eating helps retain it in the stomach, which will lead to higher exposures overall. If people are fasted, then the ratios between the anticholinergic and the procholinergic remain within target. We don't think that there's going to be a meaningful difference in tolerability between what was seen inpatient and outpatient. Furthermore, I'm sorry about the long-winded response, I will say, having a single-dose titration also means that in the real world where people may interrupt dosing, they may miss a few doses, and we're sort of not sure how that's translating for Cobenfy when people want to go back on drug. Do they have to re-titrate? Are they re-titrating? We do know that you can go right to 210 with minimal difficulty, but certainly being able to take a single dose to the target dose is quite easy with a single dose titration. Okay. That's super helpful. Thank you. Then just quickly on the, if I can jump in, if anyone was to worry that it seems like BID might have been better here than QD on the efficacy side, why the confidence in the ADEPT program that BID might be sufficient versus three times a day? Is there a correlation there that could be misunderstood? Yes. I mean, I can take that. There is an exposure with the BID. I mean, just to take a step back with respect to Cobenfy, the reason why that they've gone to TID is because of tolerability. They lowered the dose then spread it out over the day, presumably to address tolerability issues. Since this drug was well-tolerated and has demonstrated efficacy across the full spectrum of endpoints, including cognition, I think we have a lot of confidence at this dose, which is the dose that's being used in the VISTA study, that that will deliver similar results. Thank you. Thank you. Our next question comes from Sumant Kulkarni with Canaccord Genuity. Your line is open. Good morning. Thanks for taking our questions. First, do you have any specific quantitative comments you can make on how the PANSS scores that you eventually saw in ZEPHYR compare versus your expectations heading into the data? Erin, do you want to take that one? Sure. Yeah. We sort of backed into a PANSS delta. When we sized ZEPHYR, we actually sized it off the effect size of 0.5, and we had taken that deliberate sort of downgrade from what had been reported in the EMERGENT trials because we thought we would likely suffer for some expectation bias. Again, as we talked about earlier, potentially less functional unblinding. If you back that out with assumptions that we made at the time about the actual standard deviations, it would have translated into about a seven to eight-point change in the PANSS total score. With that being said, maybe I'll just reiterate something Chris has said and say it a little bit differently. We just don't think that the PANSS total score is telling the entire story, even of efficacy on the psychotic symptoms. Despite the fact that ultimately that 4.5 point difference was not quite what we had planned for in the beginning, we actually have a stronger effect on the PANSS positive subscale than our original projections would have planned for. This readiness to discharge measure, which is a really important measure of actual clinical functional outcome, and the 30% response rate, our numbers needed to treat to achieve those two outcomes are quite low, five and six respectively. On the response rate, are actually lower than the most commonly cited meta-analyses for antipsychotics. Ultimately, what that's telling us on the actual clinical impression of patient response of the psychotic symptoms and of the schizophrenia symptoms, that there's an efficacy story here that's not being fully covered in just the PANSS total score. Given that comment, do you see what you've seen so far on safety and efficacy versus Cobenfy as enough for a relatively small company like MapLight and your resources to play the commercial game in what is quite a competitive market in schizophrenia versus larger players? Or do you think the eventual difference maker for this product and the company could be Alzheimer's disease psychosis based again on what you've seen so far? I think, again, what's going to drive the commercial potential of the drug is whether clinicians like and prescribe the drug, what's going to drive that is whether patients are experiencing the benefit of the drug and they're able to take the drug. I think ultimately we have a very differentiated profile, much safer, easier to take, easier to stay on. We deliver improvement in symptoms, both on the psychotic symptoms and on cognition. I think a very well-differentiated profile that'll do well relative to Cobenfy. If I can just ask going forward, given that we're short on time and we want to get to everybody, if we can just have everybody limit it to one question going forward, please. Thank you. Our next question comes from Joseph Thome with TD Cowen. Your line is open. Hi there. Good morning. Thank you for taking my questions. Maybe can you go into a little bit more detail on the timing of some of the AEs that you were seeing in the study? As the ADP study does have a little bit of a longer titration period, do you think the tolerability will be improved in this population? Would you consider extending the titration period for schizophrenia in either ZEPHYR-2 or ZEPHYR-3? Thanks. Erin, do you want to take that one? Yes, I'm sorry, my sound went out just briefly. This is a question about timing of adverse events. Is that correct? That's right. Yeah. Okay, great. Sorry about that. Very similarly to the rest of the agents in the space, most of the adverse events that were experienced did occur early in the trial within the first one to one and a half weeks. In fact, when we looked very carefully at that, what we learned was that if you made it through the first week of treatment without having nausea, vomiting, or other GI events, you are actually very unlikely to develop them later on. I think that's obvious and also very similarly, in many patients, we do see tachyphylaxis and resolution over time. In terms of whether or not a longer titration may help and how that may translate to ADP, I think that that's reasonable. We took the one-week titration in ADP not because we saw a difference in our phase I trials between shorter and longer titrations in elderly, but because we thought clinicians would be more comfortable with a longer titration there. It is a more frail population, and it's early days, and we're blinded in that trial, but we're really encouraged by the overall tolerability that we're seeing there. We may potentially explore options for at least some flexibility in the titration. I don't know that we'll do that. We're still thinking through designs of the next ZEPHYR study. Right now, we're planning on just replicating what we're doing here. Certainly with one trial intended to be pivotal under our belt already, presumably no matter what we did, the ability to titrate with just a single dose will remain part of the allowable dosing strategy. Thank you. Our next question comes from Ami Fadia with Needham. Your line is open. Hi. Good morning. Thanks for taking my question. I wanted to better understand how you're thinking about the target exposure in VISTA, keeping in mind the ability for a one-time step down to 105 by 1.5 mg dose. Given that in ZEPHYR you saw slightly lower exposures, how are you thinking about the overall exposure that you'll be able to achieve in VISTA? Thank you. Erin, do you want to speak to that one? Thank you. A couple of things. We do still think, based on our overall C average, the response that we're seeing here, and I think the efficacy across all of the domains, not focusing entirely on that PANSS total, that the 105, 1.5 mg dose should still confer efficacy. I say this again because some of our early look at the specific domains that cross-translate between schizophrenia and ADP have some of the strongest response that we saw in the sub-analyses of the data. We think that'll translate quite well into ability to see efficacy even with a lower dose. That being said, we had very low use of the drop-down dose here in the schizophrenia trial. I think we mentioned it was only four patients who dropped down due to tolerability, and that is the protocol-driven mandate is that drop-down should be based only on tolerability. Again, so far in the blinded data for VISTA, we are seeing a similarly very low use of that drop-down dose. At this point, not only do we think it will be effective, but we are also not seeing a meaningful use of that dose. We're encouraged by the fact that most participants are making use of the higher dose. Thank you. That concludes our question- and- answer session. I'd like to turn the call back over to Chris Kroeger for closing remarks. Thank you. First off, apologies for those questions we weren't able to get to due to time. We're happy to connect with folks online and take your questions. Also just want to thank everyone for taking the time today, and for all of your questions. Appreciate it. Thank you for your participation. This does conclude the program. You may now disconnect. Good day.