Morning, and welcome to the Seelos Therapeutics Data Webcast. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this call is being recorded, and a replay will be made available on the Seelos website following the conclusion of the event. I'd now like to turn the call over to Anthony Marciano, Chief Communications Officer of Seelos Therapeutics. Please go ahead, Anthony. Thank you, Tara, and thank you for joining us this morning to discuss our top-line results from the phase II study of SLS002 intranasal racemic Ketamine in adults with Major Depressive Disorder at imminent risk of suicide. On the call today will be Raj Mehra, CEO and Chairman of Seelos Therapeutics, and Dr. Tim Whitaker, our Chief Medical Officer. We will also be joined by Dr. David Sheehan, currently Distinguished University Health Professor Emeritus at the Morsani College of Medicine, University of South Florida, and a consultant for Seelos. I will now turn the call over to our CEO, Dr. Mehra. Thank you, Anthony. Before discussing the data, it is important to mention that September is Suicide Prevention Month, and the United States is currently experiencing a mental health crisis. The CDC provisionally reported that there were over 49,000 deaths by suicides in the U.S. last year, which is the highest annual number of suicides in U.S. history. Sadly, no FDA-approved therapy exists for the treatment of suicidality and major depression. This strengthens our commitment to move forward aggressively with the end of phase II meeting with the FDA and continue to develop SLS002 for this unmet need. In our study, which enrolled adults with major depressive disorder at imminent risk of suicide, SLS002 demonstrated early and persistent clinically meaningful reduction of symptoms of depression across multiple time points, as well as a reduction of acute suicidality. In addition, at the end of the two-week safety follow-up at days 29 and 30, SLS002 revealed continued improvement, demonstrating no evidence that the symptoms return. This study enrolled 147 adults. The previous plan was to randomize 220 subjects, but the study had to end earlier due to financial constraints, and therefore the statistical powering of the study was somewhat reduced. This will be discussed in more detail later. SLS002 was well tolerated, with no evidence of new or unique adverse events, and no deaths reported occurred in our study. This differentiated and well-tolerated safety profile of SLS002 highly underscores this product's uniqueness, as well as the IP and potential for the treatment of acute suicidality and major depression. We look forward to advancing our potentially life-saving therapy toward the first FDA approval for these patients. I would now like to turn the call over to Dr. Tim Whitaker to review the data. Tim? Thank you, Raj. Good morning, everyone. Thank you for your time today. Again, my name is Tim Whitaker. I'm in the role of Chief Medical Officer at Seelos, and I want to give a brief summary of my background just to put this data and the discussion we'll have into context. I'm a board-certified psychiatrist, and after completing a fellowship in psychopharmacology, I was full-time faculty at a university teaching hospital for approximately eight years. In that role, I ran the inpatient psychiatry service. We had a 14-bed locked unit and a 16-bed open unit. I also ran an outpatient tertiary referral psychopharmacology clinic. During that time, I've seen countless patients who were acutely suicidal in various settings: the emergency room, the inpatient service, and the outpatient setting. I fully understand the limitations of current treatments and the huge unmet need. For the last approximately 26 years, I've worked in the pharmaceutical industry, almost all research and development, nearly all in neuroscience. I've been fortunate to have excellent teams to work with and excellent assets, and have approximately 21 approvals between NDAs and SNDAs, as well as some global approvals outside of the United States. And I'm convinced from the data that we'll be discussing today for this particular program, SLS002, that this is the right asset, and we have the right design, and we have the right and highly experienced development team to move this forward. And this is certainly the most important program I've ever worked on based on this target indication. I also think this drug has the best potential of any that I've ever worked on to actually be transformative to the field of psychiatry, the field of medicine, and to save countless lives. So let's begin on slide number with the study design. First of all, the part one open label portion was completed in early 2021 and was our initial proof of concept. It gave us confidence that the drug was safe and well tolerated in the target population and also showed very meaningful, robust, and rapid improvement in depressive symptoms and also in the various suicidality scales. So we were confident in the dose and the design. Part two, which we'll be presenting the results today, is a double-blind placebo-controlled trial which randomized 147 subjects with acute suicidal ideation and behavior. As Raj mentioned, the previous plan was to randomize 220 subjects, but unfortunately, the study had to end earlier. Now, these patients are severely depressed and severely suicidal to the point that they need to be hospitalized because of their imminent risk of suicide, and they required hospitalization for at least the first week or so. So it's determined that they were unable to be managed safely as outpatient for this trial. We have several rating scales that ensured that they met these criteria, both the screening and baseline, as well as the criterion that these participants made at least one previous suicide attempt. So this was really a very at-risk population. At the end of the first week in hospital, if it was judged that they were safe to leave the hospital, they were discharged and continued treatment as an outpatient for the remainder of the study. All of these patients received clinical standard of care for the duration of the study, from the beginning through the end, meaning that they all need to be on some other form of a background antidepressant medication, which could either be a new medication, an altered dose if they were already on an antidepressant, switching to a different medication, or adding an Adjuvant. Again, typical standard of care for this population. These patients all received double-blind study drug, either active or placebo intranasal spray in a one-to-one randomization on top of their clinical standard of care. They were dosed twice weekly and received a total of five doses, with their last dose on day 15, and then one of the key efficacy assessments was completed on day 16 to demonstrate the persistence of effect. Then, as Raj said, the patients have been followed for an additional two weeks for safety, but we also continue to measure efficacy during that time. Let's get right into our data. What we see here is the Montgomery-Åsberg Depression Rating Scale, the MADRS, which is a gold standard depression rating scale and our primary outcome measure for this study. The MADRS is a 10-item scale, each item 0 to six, with total score ranging from 0 to 60. To orient you to this graph, the green line is the 002 given on top of standard of care, and the red is placebo on top of standard of care. It demonstrates a very rapid reduction in the depressive symptoms on 002 that persist through day 16. There's a meaningful separation from placebo at essentially all time points where efficacy was assessed the day after dosing. That would be at day two, day five, day nine, and day 16. Note the highlighted time points with asterisk, in which the difference from placebo on the days after dosing are statistically significant. One note is on day two, 24 hours after dosing. This was our predefined primary outcome measure, and this is the point that fell slightly short of achieving statistical significance. I'll speak more about that shortly. A separate and relatively minor point, day six is not a day after dosing as it was for the other assessments. On that day, the MADRS was completed to assess whether the subject could be safely discharged from the hospital. We believe the placebo increase likely reflects that they were eager to leave the hospital on that day. I also want to point out the sample size down below in the right corner. On day 16, there were 63 subjects continuing at that time on active drug, while only 55 on placebo remained in the study, which is strongly supportive that the subjects on active drug were doing better. Next slide, please. I want to highlight the predefined primary analysis, which is the ANCOVA, thus the analysis of covariance, statistical analysis of the MADRS at 24 hours post-dosing. So this ANCOVA analysis of covariance is an analysis where the baseline MADRS score is included as a variable in the statistical model. This is typically done in depression trials, and it usually makes the analysis more powerful. Noting that four hours after dosing, there's a very meaningful and rapid reduction on the active drug compared to placebo and a very robust and significant p-value. Now, for our predefined primary endpoint at 24 hours post-dosing, using the ANCOVA, the change from placebo was minus 3.3. This fell short of achieving statistical significance at that point. It just narrowly missed. And we know the one reason why this predefined primary endpoint at 24 hours post-dose failed, and that the study was underpowered: 147 patients instead of the planned 220. However, if you look at the following data up to day 16, there was continued improvement over time and an even more meaningful separation from placebo that was statistically significant. Next slide, please. On this slide, we look at the observed data using simple group means and not adjusted means as done in the various other analyses performed. Here, at 24 hours after dosing, there's even more meaningful separation from placebo, reduction of 3.7. And focusing on day 16, there's continued improvement on active drug and even wider separation from placebo. This 5.7 difference from placebo is very robust and larger than is typically seen in most depression trials, especially this early in treatment. Another important point to note is that when the dosing was stopped on day 15 and the patients were followed for an additional two weeks, that they continued to demonstrate improvement. The mean MADRS change goes from minus 28 on day 16 to minus 30 at day 30, which is the end of the study, and this average decrease from a baseline of 38, you see the baseline at the top, down to approximately eight, is again a super impressive reduction of depressive symptoms. The day 30 group mean is now in the remission category. This demonstrates that when the drug is stopped, patients do not have recurrence of symptoms or potential rebound, which is great news. They continue to improve over time even after dosing was stopped. So again, a very rapid reduction and a persistent reduction. Next slide, please. Here we present two different analyses of our primary endpoint collected at 24 hours post-dose: the ANCOVA and the ANOVA. These are two different statistical analyses to understand the data. With the ANCOVA, as you've already seen, when the baseline variable of MADRS score is included, there's a 3.3 change from placebo with a p-value of 0.69, narrowly missing statistical significance. We conducted an exploratory analysis looking at just a simple t-test of the active drug versus placebo that does not include the baseline MADRS. And even with only 147 subjects, the treatment difference of 3.6 from placebo does meet statistical significance with a p-value of 0.49 when analyzed that way. We continue to explore the reasons why the ANCOVA, which is typically a more powerful analysis, produces less significant results than the t-test. We plan to evaluate and agree on the analysis method that we will use for the next study with the FDA. Next slide, please. This is a critically important slide and very impressive data. Here I want to highlight the response and remission rates at the end of two weeks. These are standard definitions in the field. MADRS response is defined as a 50% reduction from baseline in the score, and remission is defined as a MADRS total score less than or equal to 12. Remission is always the goal to achieve clinically. To my knowledge, these are some of the most robust rates ever seen, especially after only two weeks. We know that at baseline, these subjects were roughly at a 38 score on MADRS, severely depressed, also severely suicidal, and there's a 62% are in remission at day 16. There's a very high remission rate, basically double what was seen in the placebo group, and occurred very early. Again, and highly statistically significant. Okay, next, let's shift the focus to the all-important data on suicidality. This was another key outcome for this study that is to show a very acute and meaningful reduction in suicidality. We had several scales to look at this. One was the Sheehan Suicidality Tracking Scale, and the total score is a 13-item scale, each item from 0 to four, with four being extreme, and a total range of 0 to 52. At four hours after dosing, there was a very rapid reduction from a baseline mean score of approximately 21 and reduced approximately 15 points, and this continued for the first 24 hours. Again, a very rapid reduction and a meaningful separation from placebo that was highly significant. This is a huge finding. We also looked at the Clinical Global Impression of Severity for Suicidal Ideation and Behavior, the CGIS-SIB scale of one to five. One is none, and five is among the most extreme, so severe is a four. These patients had to be at least a four to enroll in the study. We see at four hours showed a very meaningful difference that moved in the same direction, both clinically and also statistically from placebo, and then at 24 hours on the scale, the p-value was 0.1. Once again, we know that this was that with the same difference from placebo, if the study had been able to run to completion with 220, this would have also been statistically significant. So the next slide, please. So in addition to showing a clinically meaningful effect on these scales, we've done additional statistical analyses to confirm that with the same differences from placebo, with the planned full power of 220 subjects, we would have been statistically significant on all of these relevant time points. If you look at the MADRS day two, 24 hours with 147, the p-value with ANCOVA 0.068, but with 220 patients, it would have been 0.025. The MADRS day 16, we've already seen, was robust with 147, would be more so with 220. The Sheehan score, very robust at 24 hours, would have been even more so. The CGI also that narrowly missed with 147 would be significant with the 220. Next slide, please. Now I want to shift topics to the safety data. This data further supports a very favorable safety profile for 002. You'll see that 53% of the patients on the active drug had at least one treatment-emergent adverse event. This means that 47% did not have an adverse event, which is unusual in a trial such as this. Of those adverse events that were reported, almost all were mild to moderate, very short-term transient. There were no new or unique adverse events identified from a safety standpoint. Most importantly, there were no deaths. Now, the adverse event profile of Ketamine is well known and with three different types of adverse events that are the most common. And number one is the potential for dissociation, which is a disconnection with reality or feeling dreamlike. The second type of adverse event is blood pressure elevation, and the third is sedation. Most of those side effects tend to be in parallel with the plasma concentration profile, in which this drug reaches its peak concentration around 40 minutes after dosing and a very short half-life of just a few hours. What we've seen in this study for those three types of adverse events appears to be much less pronounced than has been typically reported in other Ketamine or Ketamine analog trials such as Esketamine. Next slide, please. What we see here is this is around dissociation. So the CADS. The CADS is the Clinician-Administered Dissociation Scale, a 23-item scale with items ranging from 0 to four, 0 being not at all and 4 being extreme. So the total score ranges 0 to 92. A total score greater than four is what has been determined to be clinically meaningful dissociation, again, meaning disconnected, dreamlike, altered senses, and the like. And this data demonstrates that the highest reported CADS score were on day one, around 40 minutes after the first dose, which again is at peak plasma concentrations. And the placebo-adjusted difference is only 3.9. So it's less than the threshold of clinically meaningful dissociation, and it shows that at one hour, around 20 minutes later, it had dropped dramatically and two hours essentially nonexistent. On the second day of dosing, which was day four, again, at peak concentration, the number was even lower than it was on day one. On the third day of dosing, even lower at peak concentrations. So we've been very reassured by this data. Next slide, we want to look at the hemodynamic effects. As we know that Ketamine can increase blood pressure, and we reviewed the vital signs and adverse event carefully. We did have a handful of patients that had an adverse event of either increased blood pressure or hypertension, depending on how the investigator coded it. They were all mild. I said one was moderate. All were transient and resolved. And when looking at the mean vital sign data, there were quite minimal systolic and diastolic blood pressure changes. The baseline mean was around 123, and the maximum mean values that were reported were around 127. This was on days one and 11 at the one-hour post-dosing time point, again, correlating roughly with maximum plasma concentrations. And for diastolic blood pressure, baseline mean was around 78. The maximum mean was 81, again, one-hour post-dose. These are very minimal changes that stayed well within the normal range and considered not clinically significant. Finally, the other potential adverse event, which is common for Ketamine, is sedation. The study assessed sedation using the modified Observer's Assessment of Alertness and Sedation scale, the 0 to five scale. On that scale, anything less than fully alert at five is considered sedation. This was observed approximately 15 minutes after dosing on day one and attenuated over time. Of those that were less than five, the majority were at four, which means that they had a slight lethargic response to the name-calling normal tone. Again, short-term that attenuated over time. Next slide, please. Conclusion. While the trial did not meet its predefined primary endpoint, we did demonstrate very early and persistent improvements on depressive symptoms. All time points showed clinically meaningful differences over placebo and statistically significant differences at a majority of time points. The predefined primary endpoint, ANCOVA at 24 hours after dosing, would have met statistical significance with a larger planned sample size. Then separately, at day 16, which is required to demonstrate persistence of effect, demonstrated both clinically and statistically significant reductions in depressive symptoms. What was quite clear were the very remarkable rates of response and remission at day 16. In addition, the improvements on the MADRS were maintained during the safety follow-up. SLS-002 also demonstrated clinically meaningful reduction in acute suicidality over placebo. It was statistically significant at the key time point of 24 hours after dosing with the Sheehan Suicidality Tracking Scale, and at four hours after one dose with the Clinical Global Impression and Severity of Suicidality. These results demonstrate meaningful clinical benefit on the key measures of depression and acute reduction of suicidality. In addition, the treatment showed a very favorable safety profile. No new or unique adverse events were identified, and all subjects were maintained safely through the study. There were no deaths. We look forward to our discussions with the FDA in advancing this critical program. With that being said, I would like to welcome and turn the call over to Dr. David Sheehan. Dr. Sheehan, thank you for being here, and on to you. Thank you, Raj and Tim. Let me now give you my overall comments on this research as the external consultant to Seelos. There is no medication approved by the U.S. Food and Drug Administration or by any regulatory agency internationally for the treatment of suicidality in any mood disorder. This is the first study to be submitted in pursuit of an indication for an anti-suicidality effect in any mood disorder that has shown a statistically significant difference between the study medication and placebo on a pre-specified outcome measure of suicidality. There was a 3.4 point difference between drug and placebo at the primary time point, 24 hours after dosing, on the SSTS suicidality scale. This is a large effect by any standard on any scale. This scale measures suicidality items such as ideation, impulses, plans, intent, behaviors, and other domains like time spent in any suicidality. The results of the five-point Clinical Global Impression of Severity scale for Suicidal Ideation and Behavior were directionally consistent with these findings. The patients in both parts of this Seelos study, open-label and double-blind placebo-controlled, were severely and persistently suicidal at the start of the study. This was reflected in their high scores at screening and baseline on the suicidality scales, in having a previous suicide attempt, and in the duration of their suicidality pre-study. Suicide is a leading cause of death associated with psychiatric disorders. It is a leading cause of malpractice suits against mental health professionals. Being able to treat it effectively and quickly is one of the biggest unmet needs in psychiatry. To have a treatment with the potential to change that in four hours and in 24 hours is a landmark finding and, in my opinion, a game changer. The magnitude of improvement noticed on the key depression scale, the Montgomery-Åsberg Depression Rating Scale, was also impressive, demonstrating robust response and remission rates at day 16. This is so despite the study only having funding to complete 67% of the subjects originally intended. These results further my confidence that the Seelos team designed the right anti-suicidality study with the appropriate power to detect statistically significant differences between drug and placebo. They have an excellent asset to meet the pre-specified primary outcome measure for depression and suicidality. But what pleased me more than anything else is that the team put so much thought and effort and mitigation strategies in place to ensure that the study would be done safely without a single death by suicide in the study. These are very challenging studies. The Seelos team have shown that they are able to conduct these studies safely despite the severity of suicidality in the study subjects' pretreatment. Seelos and the SLS- 002 is leading the way in developing a treatment with anti-suicidal and antidepressant properties. If replicated in future studies, this will be a landmark and transformative achievement in psychiatric medicine. Now back to Raj for closing remarks. Thank you, Dr. Sheehan and Dr. Whitaker. In closing, I wanted to reiterate that SLS- 002 is a potentially lifesaving treatment with clinically meaningful improvement on both depressive symptoms and acute suicidality, as shown across many different scales. These data also support that this drug appears to be both safe and well tolerated. We look forward to meeting with the FDA for our end-of-phase II meeting and then subsequently conducting the phase III program. We know that we have the right asset, the correct study design, and the right team, which is experienced to move this program forward. We are excited about the potential that these results have demonstrated, and we are committed to bringing this treatment to market with the hope of eventually saving countless lives. Let me now turn the call back to the operator. Thank you, Raj. At this time, we will be conducting a question-and-answer session with our speakers. I'll now turn the call over to Anthony to read the questions. Sure. Thank you, Tara. Let me just compile these. Give me one second. Okay. Our first question comes from Charles Duncan from Cantor Fitzgerald. Your data in suicidality looks interesting, as does the MADRS responses over time. I'd like to know, was there any phenotypic information about the patients where the drug worked the best? Are there any discernible differences in severity or prior experience or concomitant therapy that you can use as you design, power, and conduct your next study? Let me ask Tim to take this call. Yeah. Yeah. In terms of right now, the data we've released is our top line, sort of hot off the press. We will certainly be doing the types of analyses that you requested, but trying to understand, are there predictors of response, certain subgroups, certain concomitant medications, and so forth? We don't have that at this point, but we'll be certainly understanding that to see if there is a way to tweak the next study moving forward. At this point, you look at the overall group means, again, robust both in depression for the group and also suicidality. If there are some predictors of response, we want to understand that better. We will be analyzing our data in more detail. We're doing that at this time to move it forward. Once we have that, we'll be able to have more dialogue on what that potentially means. Okay. Our next question comes from Tom Shrader from BTIG. Congratulations on the remarkable advance in treating ASIB. I'm not sure I've seen a more positive "negative" trial. I have two questions. Can we get some color on why the primary endpoint was chosen? And did you see a similar effect or better efficacy in the more suicidal patients? So the answer to, first of all, thank you for your comments. The reason the primary endpoint was chosen, this was in dialogue with the FDA. They said, in this population, first and foremost, because of suicidality being most commonly associated with major depressive disorder, they said, first of all, you need to show that the drug has antidepressant effects and does so acutely and persists. So it was the FDA that said, we need to have the MADRS depression as our primary. And also, we need to show persistence, that if the depression is responding rapidly, does it persist? And then in addition to that, to be able to highlight the suicidality acutely. And this is the target indication, really going after acute suicidal ideation and behavior and to be an early intervention, a lifesaving drug, and so forth. But it was really hand-in-hand with the FDA based on the target population we're after. There was a second part to your question, Anthony, right? Yes. Was there any effect shown in the more highly suicidal patients? That's an additional analysis that we'll be looking at to add suicidality as a covariate to the analysis to understand that. Does baseline suicidality severity impact the results? This is an additional analysis that we are exploring at this time, and we don't have those results yet, but it's an important one to understand. I wanted to ask Dr. Sheehan, on your suicidality scale, that 3.4 delta observed at 24 hours between the drug and the placebo. If you can expand on the clinical significance of that, what does this mean in suicidality patients? Well, that, as I mentioned, is a big effect by any standard on any scale. So a scale with this spread of number of points, you would be happy in most trials to get a two-point separation. So when you see a 3.4-point separation, that's bigger than one would expect and certainly occurs at a much earlier time point than one would expect. To put it in perspective, with the Montgomery-Åsberg Depression Rating Scale, which has a similar spread of points, over an eight-week trial with a standard antidepressant, you would expect a two-point, sometimes a little bit less, sometimes slightly more, but usually around two-point spread. Everyone would be very excited with that effect after eight weeks on a standard antidepressant across a 60-point scale. So in this case, you're getting that effect in the first four and then 24 hours at 3.4-point spread between drug and placebo. So that's not only a significant point spread, but it's statistically significant. In other words, it's highly unlikely to be a chance effect. And it's occurring even though the sample size was only two-thirds of the originally intended sample size. So that's mind-boggling, frankly. It's really a stunning effect. And keep in mind that suicidality and depression are not the same thing. People assume that you have to be depressed to be suicidal. That's not so. People think that suicide and depression are identical twins, but they're probably more likely to be cousins. And so you can have an effect on suicide and not have any effect on depression. This happens sometimes, for example, with Lithium. Sometimes you can have the depression get better while the suicidality gets worse, which you see on antidepressants in children and adolescents. So the two of these phenomena do not go in tandem together in many different trials with many different classes of drugs. Here, what we're seeing is both moving in tandem in the same direction, but the effect is bigger on the suicidality than it is on the depression. That's very illuminating. Thank you, Dr. Sheehan. Back to you, Anthony. Sure. Our next question, how does the data compare with other drugs like Esketamine or Psilocybin therapies? Yeah. I'm happy to take that. So first of all, one must be careful when comparing across studies, when comparing and certainly across molecules and also different patient populations. Much of the data for Esketamine and Psilocybin is either just depression or in treatment-resistant depression. The other thing I do want to give applause to Janssen for the work they've done to advance the field. As a former clinician, to actually have a new treatment option for TRD and also that they've done a study somewhat similar population to what we presented today in patients that are at imminent risk of suicide. And they showed that the depression got better with Esketamine. Unfortunately, the suicidality did not. But with those caveats, if you look at, I think there are three key differences than what we've seen demonstrated in our data from what is reported in the literature, the publications for the Esketamine, and also in the label. Number one is we have a more robust response on the MADRS. Our remission rates are absolutely remarkable, and they're meaningfully higher. Our 16-day remission rates are meaningfully higher than the four-week remission rates in the ASPIRE studies. Number two, and most importantly, we had a very significant reduction in acute suicidality. They did not. And number three, if you look at the safety data that we presented today versus what's in the label and the publications for Esketamine, those typical Ketamine adverse events are much less pronounced with our molecules. So to my thinking, they advanced the field, and this data is really taking it to a much higher level and a much higher bar. Thank you, Tim. If I can add to that, if we also see the slides that we have shown on day 16, the MADRS responders and remitters. So 75.7% responders in two weeks after five doses are clearly by far we have not seen, and I would love to get Dr. Sheehan’s viewpoint on that as well. That's remarkable. After just five doses in two weeks, 76% responders. Generally speaking, if you compare across other studies, that number is way higher, at least 50% higher, if not more. And same thing for remission, 62%. That's the clinical goal. So Dr. Sheehan, your thought on those 62% remission and 76% responders on day 16 after five doses in MADRS? Yes, Raj. I agree with you fully. I have not seen such impressive data at such an early point in any depression trial that I can ever recall. Thank you. Anthony, back to you for more questions. Yeah, sure. Next question is from Eddie Hickman at Guggenheim Partners. Thanks for hosting the call. And nice to see positive data. Can you speak at all to the number of patients that were screened out of your study prior to enrollment? And are there any changes you can make to improve that process going forward? Tim? Yeah. The exact number prior to enrollment, I do know that in between people, patients who met criteria at screening, who no longer met them at baseline, was 21, and that was because their severity of suicidality symptoms or depressive symptoms once they were in the hospital had diminished. This was one of our key design criteria, is that they needed to meet the same severity at screening and baseline. We did have, of course, other patients screened out because of either medical conditions such as substance abuse or that they had something like abnormal labs, abnormal electrocardiograms, and so forth. I don't have that exact number. We have that. I just don't have it off the top of my head, but so that would be usual and standard. People that don't meet the inclusion or exclusion criteria based on medical conditions, comorbid substance use, or they don't meet the severity criteria. So to add to that, Eddie, I think as you just saw that we have screened out 21 patients. Can we further improve that? I think our process works. Many of those patients were screened out because they were responding and not meeting the criteria pre-randomization. So I think the process works. If I were to give you my summary, if you look at day 16, the effect size is just absolute numbers of the drug, MADRS going from 38 to 10 on a Sheehan scale, starting from severe suicidality at 21.4 going to 1.3. Similarly, on CGIS, four going to 1.4 and one being the normal bottom. The drug did what it's supposed to do. And these are massive numbers. The reason we are apologetic on the data is only one and one conclusion that it was underpowered because of the financial constraint. We did not finish the full study. If we had, and remember, almost all the studies that even in depression, leave alone in this indications, they generally enrolled at least 225-plus patients. All the ASPIRE 1 and ASPIRE study, ASPIRE 2 study was also 225 patients. And all the other MDD studies are done with 225 to up to 550 patients. So 147 patients, clearly, I think the only conclusion this drug did what it's supposed to do, it was underpowered. Any other thoughts on that, Dr. Sheehan, overall? Just to put it in perspective, what they showed you on Slide 11 was a power analysis. Effectively, what the power analysis does is it says, if the data had continued as we see it in the first 147, how many more patients would have been necessary to achieve the statistical significance that was missed in the underpowered study? What you can see here is that if the numbers had been short of the originally planned ones at 200, there would have been statistical significance on all of the primaries. At 220, it would have been even more significant. This is not likely to be a chance finding. It's clear that all of these primary endpoints would have been met if there had been adequate funding and the studies had continued in the same manner that they had in the original 147. That's the point of the power analysis. Thank you, Dr. Sheehan. Anthony? Sure. We have a follow-up from Charles Duncan at Cantor. The first question is, the ANCOVA versus ANOVA results, do we have any thoughts on why that was divergent, and what are the next steps as far as meeting with the FDA? I will take the first part and then refer the FDA part to Tim. So the ANOVA analysis that we did, and it shows observed differences, that's what we observed between placebo and the drug at 24 hours was 3.6, and the p-value is 0.049. Unfortunately, that analysis, although accepted by the FDA, but it was not pre-specified, so we did that. Now, why did the ANCOVA analysis depress the treatment differences from 3.6 to 3.3, and the p-value got worsened rather than improved? So, typically, if you look at the FDA's guidance on covariate analysis, they predict that the covariates are used to improve the p-value and reduce the sample size. That's generally observed. In this case, the covariate was baseline MADRS and change in MADRS. And all the data from the depression study shows the following: that higher the baseline MADRS, the more depressed you are, the more change in MADRS would happen upon a therapy. And lower the MADRS, you'll see less change in MADRS. In this case, for some reason, we did not see a positive correlation. We saw a negative correlation. Now, it is hypothesized. It is possible because this is not a purely depressed population, but because this is a depressed and a severely suicidal population. So Dr. Sheehan, please comment on that, and then I'll move the FDA part of the question to Tim. Yes, exactly, Raj. That just because somebody is more severely depressed doesn't necessarily mean they will be more suicidal. That's a common assumption that frequently, in fact, does occur. But you often see people who are mild or only moderately depressed who are very suicidal, and you see people who are often very depressed and maybe even not suicidal at all, so these two things disconnect from each other, and since we were mainly targeting and focusing on this suicidality piece of this story, that was the focus in capturing the population for study that may have contributed to this deviation that you're asking about, so Charles, these are again qualitative observations because there have not been many studies done in suicidality, so we don't have the quantitative observation that we can back that, but the qualitative observation you just heard from Dr. Sheehan. Anthony, can you repeat for Tim's purposes the FDA part of Charles' question? I guess it was, what are the next steps in timing for discussions with the FDA? Yeah. So we have our briefing book, background document that we're working on right now, that's in the works. And we'll be reaching out to the FDA to set up a meeting. Our goal is to meet with them by the end of this year and to discuss our next steps and what additional data they need for our submission. So bottom line is it's in the works, and we certainly are planning to meet with them by end of year. Thank you. Anthony, any further questions? I think a lot of the remaining questions we've addressed about the data. I guess one question on a kind of bigger view for you, Raj, is what are the other upcoming milestones for the company, so we have finished, completed enrollment in the ALS study, and we are about to data lock that study, and that data should be out by year end. Of course, that data is being collected by Healey Center, our partner, and the current predictions from them is the data should be available, and they completed 160 patients' ALS study by year end, so thank you with that. But before I conclude the remarks, I wanted to hear Dr. Sheehan's overall parting remarks and any remarks that Tim may have. Well, I'm delighted, as I said, that you succeeded with such a severely suicidal population to keep the study safe. That was at the center of everything. We worried about that a great deal. And even in studies on major depressive disorder where suicidal patients are screened out, you often see suicide attempts and, unfortunately, some deaths by suicide. This did not happen in this situation. And the other thing is, as I say, this is, I think, a landmark finding because it's the first time, to my knowledge in psychiatric history, that anyone has shown a statistically significant difference between drug and placebo on an anti-suicidal effect. Thank you. Thank you, Dr. Sheehan. In my viewpoint, if I dare say, I think we have an asset. And this is a huge unmet need. And we'll pursue this. So we will discuss with the FDA at the end of phase II meeting what the next steps are. And this time around, complete the study with the fully powered design that we originally had. Tim, any parting thoughts before we conclude the call? Yeah. No, I just want to thank everyone for the time this morning, especially Dr. Sheehan for all your guidance and input, our clinical development team, but I just want to echo what has just been said. I'm really confident in this asset. I know we have the right design, and we know what the right power will be, and we have the highly experienced team to move this forward, so we're excited to meet with the FDA on next steps. Thanks again, and I hope everyone has a great day. My parting thought will be we did not discuss too much about safety. Our drug is truly differentiated in safety, and this completely underscores our IP, which is, "This is not your father's Ketamine," as I jokingly say. Thank you, everyone. We look forward to updating you in the near future after our dialogues with the FDA. Thank you again. Thank you, Dr. Sheehan. It's a pleasure. Yeah.