Good morning, and welcome to the Alto Neuroscience Investor Conference call to discuss the company's acquisition of a novel dopamine agonist combination product candidate. At this time, all participants are in a listen-only mode. Later, we will conduct a Q&A session, and instructions will follow at that time. As a reminder, this conference call is being recorded. I will now turn the call over to Amit Etkin, Founder and Chief Executive Officer of Alto Neuroscience. Amit, please go ahead. Thank you, Operator. Good morning, everyone, and thank you for joining us to discuss the acquisition of a novel dopamine agonist combination candidate, which has a potentially pivotal trial readout in treatment-resistant depression within our current cash runway. The press release was issued pre-market this morning and can be found on the investor relations section of our website, altoneuroscience.com. Before we begin, I'd like to remind you that today's webcast contains forward-looking statements and would refer you to our most recent 10-K and our other filings with the SEC, which are available from the SEC's website or on our corporate website. Joining me on the call is Nick Smith, our Chief Financial Officer and Chief Business Officer, as well as Dr. Michael Browning, Professor of Computational Psychiatry at Oxford University, and Dr. Alan Schatzberg, Professor of Psychiatry and Behavioral Sciences at Stanford University. I'll begin with an introduction and overview of the transaction, diving into the details behind the opportunity for ALTO-207, formerly known as CTC-501. ALTO-207 builds on compelling pramipexole data, and to expand on that supporting literature, Dr. Browning will discuss results from the recently completed PAX-D trial of pramipexole in patients with treatment-resistant depression, or TRD. I will then review the clinical development path for ALTO-207, including results from completed phase I and phase IIa studies conducted by Chase Therapeutics prior to today's acquisition. Before we open the call for Q&A, we'll also hear from Dr. Schatzberg, who will expand on the treatment-resistant depression landscape, high unmet need for patients, and opportunity for a new combination product. We are a company entirely focused on developing biology-driven medicine for neuropsychiatric conditions so that each patient can get better faster by leveraging an understanding of individuals' neurobiology. The opportunity with ALTO-207 fits squarely in this mission. We are very excited about the opportunity and data behind the acquisition of CTC-501, targeting treatment-resistant depression, as well as CTC-413, targeting Parkinson's. Both of these products have completed successful phase two studies and add on to Alto's already deep pipeline of novel assets. Our focus today is the data and development plan behind CTC-501 and what this product could bring to a very high-need group of patients, fitting perfectly within our overall approach and pipeline. There are several areas at Alto where we have gained unique leverage through our biomarker approach, namely cognition and dopaminergic function. The acquisition of CTC-501, now known as ALTO-207, was driven by Alto's proprietary insights on dopamine biomarkers in depression and how to best use them to modulate this critical brain system. It adds a late-stage, potentially pivotal TRD readout with a clinically validated mechanism and, as a consequence, a high probability of success. It also fits well within our pipeline, including our focus on dopaminergic modulation across several assets. The deal terms include a $1.75 million upfront and then milestones totaling under $72 million across development, regulatory, and clinical success milestones. This deal structure mitigates near-term cash impact, allowing us to deliver the phase IIb readout within our current cash runway, which continues to fund us into 2028. Throughout this presentation, I'll refer to CTC-501 as CTC-501 and ALTO-207 with work completed by Chase labeled as CTC-501 and future plans as ALTO-207. As you can see on slide seven, our pipeline is deep with late-stage assets. Above and beyond the excitement about what ALTO-207 brings, we have great confidence across our programs and the opportunities they represent across disorders. The latest addition to it simply complements the others with a late-stage, independent, and high probability of success asset. With ALTO-207, we now have five phase two readouts in the next two years, including now three phase IIb studies targeting different mechanisms for different populations, with all programs on track and data expected across the next two years or so, all within our cash runway, which remains into 2028 even after this acquisition. Overall, we believe that this transaction is a strong strategic fit for Alto and continues to position our platform for substantial value creation and long-term growth. Pramipexole, the dopamine agonist component of ALTO-207, has clear evidence of robust antidepressant activity, but equally clearly is limited by significant tolerability issues when used alone. By combining pramipexole with the antiemetic ondansetron, which blocks a key pathway that mediates pramipexole's intolerability, CTC-501 demonstrated clear safety benefits along both for higher doses in phase I and strikingly five times faster titration to get there. A phase two study with CTC-501 resulted in large and statistically significant clinical effects relative to placebo in depression, demonstrating the tolerability and clinical benefit of the combination strategy. As a result, we plan to launch in 2026 a potentially pivotal phase IIb study in TRD with top-line data expected in 2027. The regulatory pathway for this product, relying on the 505(b)(2) process, is likewise straightforward, shortening the time to market. You can easily see this product hitting the market in just a handful of years. All of this is a strong setup for a high probability success development path for a population, treatment-resistant depression, that is of very high need, setting up a compelling clinical commercial case protected by strong IP positions. We also build on success of analog cases for combination drugs in psychiatry, such as Auvelity and Cobenfy, giving us confidence in the regulatory and commercial path ahead. Let's dive into the science behind this excitement. As you can see in slide 10, dopamine has multiple roles in depression. It relates to cognitive abnormalities, motivational and reward deficits, and psychomotor abnormalities. We've done extensive work to understand and validate both EEG and behavioral markers of dopaminergic function, which we have already deployed in our trials. We have taken two complementary approaches to modulating dopamine. The first is an indirect approach. Think of this essentially like a game knob where you try to preserve endogenous activity patterns but turn them up. The advantage is that this is associated with fewer dopamine-related adverse events. The challenge is that the effects are more subtle and depend on the specific dopamine strategy taken, examples for which are ALTO-203 and ALTO-300. Today, we're talking about a direct receptor stimulation approach that seeks to achieve supraphysiologic stimulation, focusing in particular on D3/ D2 receptors, which therefore has the potential for outsized efficacy. With that comes a higher rate of dopamine-related intolerance and adverse events directly due to D3/ D2 agonism in other brain regions. Historically, an early approach at Alto focused on low doses of a dopamine agonist combined with another drug to try to get synergy in the target brain area while avoiding off-target effects on other brain regions. Examples are ALTO-204, ALTO-205, ALTO-206. Today, with ALTO-207, we're taking a high-dose approach with a dopamine agonist using an antagonist targeted to the mechanism driving agonist-related intolerance, here ondansetron, to mitigate nausea and vomiting. As I mentioned, our pipeline includes multiple mechanistically distinct compounds that converge on enhancing dopamine function in different ways. All modulate some aspect of dopamine release with a specific mechanism that complements effects on dopamine release, giving us flexibility to address specific symptom profiles and biological signatures. For example, ALTO-300 includes melatonin agonism affecting sleep and circadian rhythm. ALTO-203 includes norepinephrine, acetylcholine, and histamine release, leading to effects on cognition and wakefulness. However, it's ALTO-207's unique profile of direct D3-preferring D3/ D2 agonism that leads to behavioral activation and prominent anti-anhedonic effects, offering potentially outsized efficacy in TRD. Over the past year, we've generated novel insights into dopaminergic biology that allow us to build on a biomarker-driven strategy. On the left in slide 12, you can see an EEG signal called gamma sample entropy, which essentially measures signal-to-noise in the cortex and predicts response to ALTO-300, and this shows that it's directly related to dopamine activity. It is inversely related to dopamine, so when you deplete humans of dopamine, you get an increase in gamma sample entropy as well as an increase in anhedonia. We then looked for which dopamine agonist could decrease gamma sample entropy because that indicates increased dopaminergic activity and came to pramipexole. As you can see on the right in rodents, pramipexole does exactly that, decreasing gamma sample entropy in a dose-related manner, which supports our mechanistic and biomarker rationale for drug selection. It also emphasizes the importance of targeting a higher dose of the drug in patients. The mechanism of ALTO-207 is a unique combination of pramipexole, a dopamine D3-preferring D2/D3 agonist approved for Parkinson's disease, and ondansetron, an approved selective 5-HT3 receptor antagonist approved as an antiemetic. Pramipexole's antidepressant effects come from two places: direct D3 agonism, enhancing the reward processing within the striatum, and D2 presynaptic agonism, which leads to presynaptic autoreceptor desensitization and, as a consequence, increased dopamine release. Pramipexole's effect on brainstem dopamine receptors, however, is what causes nausea and vomiting, which is mediated by a synergistic pathway through 5-HT3. Co-administration of ondansetron therefore blocks the 5-HT3 pathway in order to block dopamine agonist-induced nausea and vomiting. This biology also directly motivates our rapid escalation to higher doses of pramipexole in ALTO-207. Faster autoreceptor desensitization supports faster onset of action and greater efficacy. Also, receptor occupancy data suggests that there is room to go up since typical doses have relatively low receptor occupancy. To understand who may be best suited for a dopamine agonist strategy, we used a digital twin analytic approach as outlined in slide 14. First, we created a human multivariate EEG signature of the effects of supraphysiologic dopamine stimulation, a dopaminergic digital twin, by looking across many EEG measures and defining how they move in response to dopaminergic stimulation. Gamma sample entropy is one of them, as you can see in the figure on the left. As shown in the top right, we then rank these EEG features by the degree of change under dopaminergic stimulation from most increased to most decreased. We then take a patient matching approach, identifying subgroups of patients whose baseline EEG shows the inverse pattern. These patients are therefore likely to benefit from dopaminergic agonism. Think of it like a functional lock-and-key biological match between pathophysiology and drug. This matching is then quantified by a score that can be evaluated statistically. On the left of slide 15 is the dopaminergic signature sorted from the most increased EEG measure to the most decreased for visualization. On the right is what happens when you deplete people of dopamine. These individuals feel anhedonic. The brain state created by dopamine depletion is the inverse of the state created by dopaminergic stimulation. This provides direct validation of our digital twin approach and of the dopaminergic signature itself, both for the drug effect and for identifying people with low dopaminergic function. We then used our dopaminergic digital twin signature to identify which patients are most likely to respond. That is, whose brain patterns are the inverse of the dopaminergic pattern. In the top row on slide 16, the inverse dopamine pattern is seen strongly in patients with depression relative to controls and, in particular, in patients with TRD. Moreover, MDD patients characterized by dopaminergic dysfunction, as measured by our biomarkers, are a good match for the dopamine stimulation strategy. This includes patients displaying poor reward learning. Also, it includes those with high gamma sample entropy, our index earlier of dopaminergic activity. Importantly, people with high versus low placebo response do not differ in their match to the dopaminergic signature, showing that this biomarker is specific to reward processes in depression. We believe that our ability to define and detect a dopaminergic response signature and use it to identify patients most likely to benefit gives us a unique advantage in patient stratification and in development of ALTO-207. Let's now turn to the historical data that support the clinical rationale for ALTO-207. We focus for ALTO-207 on development for treatment-resistant depression. TRD is an area of tremendous unmet need. About one-third of depression patients suffer from TRD, which is about 3 million people in the U.S. annually. TRD is associated with greater chronicity, disability, and higher relapse rates and carries a tremendous burden both for the individual and to society. Unfortunately, current treatment options for TRD are very limited, primarily antipsychotic mesketamine, neither of which is particularly effective. Thus, TRD represents a critical opportunity for innovation in treatment. Slide 19 details some of the key historical data behind pramipexole. Here you see two older trials of pramipexole alone versus placebo. In both cases, titration of pramipexole was slow and followed the FDA label. Both trials, however, yielded statistically significant clinical benefit over placebo. These trials also showed an increase in intolerability, especially nausea and vomiting at higher doses, which was dose-related, as seen in the table at the bottom. Of note, one study tested 5 mg of pramipexole, but very few patients could tolerate it, leading to both a high rate of adverse event-driven dropout, but for those who could tolerate also led to greater efficacy. As demonstrated here, while pramipexole has shown efficacy at around 1 mg to 1.5 mg a day, higher doses may offer greater benefit but require a slow titration process to get there and have increased rates of AEs and dropout. There's also data on pramipexole's effects in TRD. Data from a seminal case series on the left in slide 20 shows that TRD patients need a higher dose in order to respond. Moreover, as shown by the observational data on the right, TRD patients seem to respond better to pramipexole than to drugs that do the opposite, D2 antagonist antipsychotic drugs like aripiprazole. These data position pramipexole for potential best-in-class efficacy in TRD, especially targeting a higher dose, but pramipexole is currently limited by the need for slow titration and the intolerability that increases with dose. With that, it's my pleasure to introduce Dr. Michael Browning. Mike is a professor of computational psychiatry at Oxford University, where he leads a clinic focused on TRD treatment. In his lab, he also studies dopaminergic mechanisms and biomarkers like those we've discussed. We're fortunate to hear from Dr. Browning today on results of the PAX-D study, a large TRD treatment study of pramipexole. Of note, this is the first public presentation of these results to a wide audience, and they provide strong validation for the mechanism behind ALTO-207. Mike, the floor is yours. Thank you, Amit. I'm going to tell you about the results of the PAX-D study. The design of the study is shown on slide 22. The rationale for this study came from our clinical practice, where we felt that pramipexole really had a marked positive effect size on patients with TRD, but we were questioning whether this benefit was worth the cost in terms of side effects. In order to test that, we ran a randomized controlled trial in which patients were randomized to pramipexole versus placebo in addition to their ongoing antidepressants. The primary outcome for the study was at week 12 of treatment, but we continued people in the study for a full 48 weeks that was on pramipexole or placebo to look at tolerability and the maintenance of benefit. The primary outcome was change in the self-reported QIDS-SR16 outcome, and we also measured a clinician-reported depression outcome as well as anhedonia, functional outcomes, tolerability, and we were particularly interested in people who discontinued the medication because of intolerance. We used pramipexole on its own, titrated up to 2.5 mg of the immediate release, and it took us about four weeks to titrate it up. The study was conducted across nine sites in the U.K., and patients had failed two antidepressants in the current episode and continued on at least one antidepressant. On the following slide, number 23, we can see the baseline characteristics of the participants. These were relatively typical for studies of depressed patients. There were more women than men, and people were in their mid-40s and were slightly overweight. We recruited 75 people in each group. I'd like to draw your attention to some of the characteristics of this group of patients. The median duration of their current episode of depression was about eight years, so they've been depressed for a long time, and they've had an average of between three and four antidepressants that have failed in their current episode. Their mean baseline for the QIDS, which is the measure of depression, was 16, which is the lower bit of the severe range for depression. This was quite a morbid sample that had tried lots of medication and had not been helped by it. On the following slide, number 24, we can see the outcome of the primary outcome that we measured, which was the change from baseline in the QIDS-SR16 score. The X-axis shows the weeks of treatment from randomization to week 48. The gray bar at 12, that's the time of the primary outcome. What you can see is pramipexole significantly reduces depression as measured using the QIDS quite rapidly, and by the primary outcome, it has a large effect size. That's a Cohen's d of about 0.9. The QIDS-SR is quite a commonly used self-report scale. There are published conversion tables that you can get equivalent scores of other scales such as the MADRS, and this effect size is equivalent to about a seven-point difference in the MADRS at the primary outcome. On the next slide, number 25, you can see the effect of treatment on a clinician-reported scale. That's the QIDS-C, and that shows a very similar effect. It's measured less frequently, so the lines are a bit flatter, but otherwise, it's the same. On the following slide, number 26, you can see the effect on anhedonia, measured using the SHAPS. Anhedonia is traditionally quite a difficult scale to move with treatment, but again, pramipexole has substantial benefits in it. The lower scale, the WSAS, that's a measure of functional outcome. Can the person return to work? Can they fulfill their roles socially and in their family? That's an outcome that's particularly important to patients. Again, you see a rapid and sustained benefit of pramipexole on functional outcomes. On the next slide, slide 27, we see the other side of the coin. This is the tolerability of pramipexole as we used it. On the left are the most common side effects reported by patients in either group, and you can see that nausea, vomiting are the most common side effects. On the right, we see the number of patients, or the percentage of patients, rather, who discontinued either treatment because of intolerance. Twenty percent of people randomized to pramipexole over the course of 48 weeks' treatment discontinued it because of intolerance, and that was largely due to nausea and vomiting, and the rate in the placebo group was only 5%. There is a significant dropout because of the side effects of treatment. On the next slide, 28, we see some of the other measures of some of the other side effects that can be associated with pramipexole. One of the things that we were most worried about in the study was the development of impulse control disorders. On the right, you can see a graph of the QUIPS-RS. Now, it is a self-report scale measuring impulsive behavior and impulsive thoughts, and we saw no increase of that in the pramipexole versus placebo. Even by measuring AEs during the study, there were not frequent reports of impulsivity. There were only two patients in the pramipexole group that developed mild symptoms of impulse control difficulties involving playing computer games for longer periods of time, which resulted in reducing the dose. An interesting observation of this is that observational studies of patients with Parkinson's disease report a much higher incidence of impulse control problems with pramipexole treatment in the order of about 15%. We found probably about 3% incidence, which is much lower and is in line with some observational data in depressed patients. This suggests the possibility that impulse control difficulties are less common in people with depression. I should add a caveat to that statement. In this study, we excluded people from enrolling in the study if they had any evidence of impulse control difficulties beforehand, including things like harmful alcohol use. We may be underestimating that, but it was certainly low in this study. On the last slide, slide 29, there's just some summary. Pramipexole was really very effective in terms of its reduction of depressive symptoms. The effect size is substantially larger than that reported for esketamine and antipsychotics from meta-analyses. Generally, pramipexole has to be titrated quite slowly over four weeks, and that's largely to avoid nausea and vomiting. Clearly, from the results that I presented to you, the limiting factor in the use of pramipexole clinically is the tolerability question. 20% of patients being unable to tolerate it is a barrier to its clinical implementation. The approach suggested in this call of combining it with an antiemetic is ideal, in my opinion, as primarily it will allow more patients to use this drug, which is clearly effective. We'll be able to titrate it more rapidly. It may achieve a rapid effect, and if the biomarkers that have been described earlier can be used to detect dual benefit, or perhaps even more importantly, who will develop side effects, then that will only improve its utility further. Thank you very much. With that, I'll hand back to Amit. Thank you, Mike. Those results are incredibly exciting and give us a lot of confidence in this mechanism and its validation. Let's now turn to the data on CTC-501 gathered by Chase Therapeutics to understand both the rapid dose escalation and the clinical effects and tolerability that come with it. As you can see on slide 31, to build on some of the points Mike made, in dosing, there is a need to reach the target therapeutic level rapidly while avoiding side effects that would cause premature discontinuation. We believe that ALTO-207 represents a next-generation approach designed to address limitations of pramipexole with rapid dose escalation to higher targets and the potential for robust clinical efficacy. In all prior studies, including as Mike noted in PAX-D, pramipexole followed the slow titration specified in the FDA label. The combination approach in CTC-501 with pramipexole plus ondansetron, however, allows for a fivefold faster dosing to a higher dose target than any previous study, as evidenced by Chase's phase I and phase IIa studies. On slide 32 is the phase I data supporting the safety of this approach. CTC-501 or pramipexole were titrated up daily to a target of 6 mg in just 12 days. Nobody on pramipexole alone was able to achieve this, while 60% of the same people when getting CTC-501 were able to reach the 6 mg max daily dose tolerably and no doubt could have gone higher. This led to an at least two and a half-fold increase in the tolerable dose of pramipexole with CTC-501, achieving over 4 mg on average, which is notably higher than even PAX-D was able to reach with its FDA label slow titration. These data support the ability to more quickly achieve a higher and more consistent dose level than possible with pramipexole alone. Chase then completed a phase IIa trial of CTC-501 in MDD. This placebo-controlled trial in 32 patients looked at safety and tolerability as well as effects on typical depression clinical outcomes. Titration happened very quickly, on average just eight days, to achieve over 4 mg with a maximum daily target of 5 mg per day. Up to 80% of patients achieved that maximum dose tolerably. Patients were then followed as outpatients for the remainder of the eight-week treatment period. As you can see in slide 34, the phase IIa trial showed robust antidepressant effects. By the eight-week endpoint, there was a statistically significant effect on moderate change from baseline with a Cohen's d of 1.1, reflecting a greater than 8-point delta between drug and placebo. Importantly, there's also evidence of potential rapid onset of action with a Cohen's d of 0.58 at week two. Importantly, the groups were also well matched at baseline with baseline moderate severity around 28 in both groups. The same pattern, a large effect size, Cohen's d of 1.0, and rapid efficacy with a 0.78 effect size at week two is seen in the CGI scale, an outcome that moves very little, if at all, in antidepressant trials. In the table in slide 36, you can see that nausea and vomiting were the most common AEs, which were mild to moderate. The phase IIa trial, therefore, confirms the favorable safety and tolerability profile of ALTO-207. Not only does the combination strategy support much faster dosing to a higher target, but there's also evidence of a dose-response relationship between pramipexole exposure and clinical change, as shown in slide 37. Here you can see the effect size and doses across randomized trials, with PAX-D outcomes here shown as week eight to be comparable to the other eight-week studies. The largest effect clearly comes in the CTC-501 study, but likewise, there's also clear evidence, as Mike mentioned, of consistently larger effect sizes relative to current treatment options in TRD. This suggests that ALTO-207 may have differentiated efficacy in TRD, comparing very favorably to the two principal options that these patients may receive, namely esketamine and antipsychotics with aripiprazole shown on this graph. The real-world use of pramipexole in the clinic also highlights the opportunity at hand. Data in slide 38 are drawn from NIH's All of Us data set, which includes over 100,000 patients with depression. Of these, 2,000 received pramipexole. The histogram shows the maximum daily dose achieved by each patient, the vast majority of which never even reached the 1 mg level, which is at the lowest end of potential efficacy in MDD. Virtually none reached the level needed for optimal treatment in TRD. Moreover, the time between dose escalations was very slow, on average 273 days, likely because of the adverse event limitations and the practical difficulty of titrating pramipexole alone in real-world clinical practice. ALTO-207 is therefore positioned very well for success in the planned potentially pivotal phase IIb study. First, there is a highly compelling evidence base for pramipexole's antidepressant effects in TRD. PAX-D underlines that point. However, the principal limitation of pramipexole alone is its dose-related intolerability, and this is exactly what motivated CTC-501's development. Second, CTC-501 completed a phase one study demonstrating significantly improved tolerability with fivefold faster dose escalation. A phase IIa study, a placebo-controlled study, met both of its primary and secondary inputs, showing large, clinically meaningful effect sizes. We also plan to collaborate with Dr. Browning and the other PAX-D sites in building on their pathbreaking research success. This phase IIb trial, designed like a phase III study, is planned for a launch in 2026, with top-line data expected in 2027. We also plan to take a regulatory strategy that makes use of biomarkers, as outlined in slide 40, particularly the dopamine-related biomarkers we've discussed. We'll focus on biomarkers of clinical efficacy and tolerability. We'll pre-specify them as key secondary measures in the phase IIb trial, and then we'll verify them as complementary or enrichment markers in phase III. This will leverage both our EEG biomarkers of dopaminergic functioning and our behavioral biomarkers, all of which are already employed across our studies. We anticipate a regulatory path with broad TRD approval, plus the potential for an enrichment marker to identify patients with an even greater effect. This biomarker strategy, therefore, also builds on our FDA interactions around different types of enrichment markers in the ALTO-100 program. Finally, we'll follow a 505(b)(2) regulatory pathway, which enables streamlined development and potentially shorter time to commercialization. It's now my pleasure to welcome Dr. Alan Schatzberg to provide an external expert perspective on pramipexole and a broader understanding of the patient journey and the TRD landscape. Dr. Schatzberg has held many roles in the field over his career, including serving as Chair of the Department of Psychiatry and Behavioral Sciences at Stanford University for two decades, as well as national leadership roles such as being the President of the American Psychiatric Association. He has received many honors for his research on the biology and treatment of mood disorders and is a member of the National Academy of Medicine. Alan, the floor is yours. Thank you very much, Amit, for the very kind introduction. I'm delighted to be here today to discuss this very new and exciting opportunity to develop a method for improving the tolerability of Paxil. Just to remind folks about the treatment of depression, we start with an initial diagnosis. The first-line treatments tend to be SSRIs or SNRIs still today, even though the SSRIs were first introduced a number of years ago. If the individuals show an inadequate response, we wind up either doing some augmentation with typically an atypical antipsychotic is most commonly used, but there are other strategies as well, one of which has been pramipexole. Another is to switch antidepressants to a non-SSRI/ SNRI. For many patients, we still see an inadequate response. It is kind of covered with you the importance of dopaminergic function for many patients, particularly patients with refractory depression. These individuals are typically called TRD or treatment-resistant or treatment-refractory depression. They wind up being referred to specialists such as myself or Michael Browning for comprehensive evaluation and management. Today, there are other strategies. SPRAVATO or esketamine is one. There are non-pharmacologic treatments such as electroconvulsive therapy, ECT, or transmagnetic stimulation. Next slide, please. What I think is particularly kind of has been often effective in the hands of specialists is the use of pramipexole. Pramipexole, as Amit has shown you from the studies from Browning, but even previous to that, Corrigan and Dwight Evans' studies at the NIMH have indicated that pramipexole can be quite effective. The difficulty with pramipexole is the tolerability. We now have an opportunity with ALTO-207 as a combination approach to, in fact, improve the rapidity of the onset of the response by improving tolerability and attaining higher doses sooner of the pramipexole. This can reduce patient distress and improve compliance. This combination appears to be well tolerated and orally administered, making it easier to initiate than some of the kinds of treatments that we occasionally have to use, such as intravenous ketamine. It has a mechanistic differentiation in terms of that it targets the dopaminergic system, which, as has been pointed out, is extremely important in terms of mood regulation, in terms of speed of response, cognition, and hedonic capacity. It is a mechanism of action that is not common with the SSRIs, SNRIs, and some of the other antidepressants. There is a built-in synergy with a combination drug which simplifies the treatment strategy and monitoring. When you compare it to manual slow titration of pramipexole, which requires significant hands-on clinician time and expertise, or using ondansetron separately, which would probably lead to further errors given speed of titration, this combination, which offers us an opportunity in a single formulation to help patients tolerate a very effective drug and to achieve therapeutic doses and blood levels rapidly and improve the likelihood of success and the rapidity of success. I think this is a really major step forward. Before I hand it back to Nick, let me say something about experience in using pramipexole, just so individuals out there can understand this. This is an extremely effective agent, but the doses you require are at least a milligram. Generally, they're up somewhere between 1.5 mg-2.5 mg per day. The difficulty is to get to 1 mg can take weeks. This becomes problematic for the patient and for the treater in terms of the time needed and also dosage adjustments that are often called for because of nausea and potentially vomiting. By having a combination agent which mitigates the nausea and vomiting, we have a strategy that not only is more tolerable to the patient, but it's more tolerable and one can use higher doses more rapidly. You can achieve the therapeutic doses needed to overcome a refractory depression. From my perspective, even as an experienced pharmacologist with using pramipexole, this is a major step forward for this approach in treatment-resistant depression. Thank you, Alan. It's clear from your perspective and experience in this space that TRD certainly remains an area of high need and that the novel combination ALTO-207 could be well positioned to address these needs. Before we jump into Q&A, I want to highlight a few precedents in our space that give us a lot of confidence in the potential future commercial success of ALTO-207. First, Cobenfy or KarXT is a great example of a recent approval of an antagonistic combination that highlights the value of addressing undesirable side effects while achieving larger clinical benefits in neuropsychiatric disorders, in this case, for schizophrenia. Cobenfy demonstrates that achieving larger effect sizes as compared to standard of care is a major driver in developing a novel differentiated treatment and leads to a very compelling commercial profile. The other example, Auvelity, is a great example of a synergistic combination, which is an approach to improve dosing and tolerability in depression and also highlights the value of streamlined development leveraging the 505(b)(2) pathway. This is a synergistic combination of two approved medications, and its development as a novel mechanism in depression offers a new treatment option for clinicians and patients. Both of these analogs are projected to be highly successful commercially, and the early success with Auvelity clearly demonstrates the need in depression. We believe these combination approaches pave the way for commercial success. If future results with ALTO-207 remain consistent with observed data, we anticipate that ALTO-207 could be a blockbuster product in depression. As discussed today, the acquisition of ALTO-207 is fully aligned with our efforts to advance multiple mechanistically distinct compounds leveraging our Precision Psychiatry Platform. We believe this acquisition underscores the robust value of our platform and bolsters our already strong prospects for long-term growth. We are very excited for the milestones we have ahead of us across the pipeline, with now five clinical readouts expected between now and the end of 2027. Importantly, with our current cash balance expected to fund all of these and our operations into 2028. Before we open the line for questions, I'd like to extend my gratitude to the Chase team for their work in developing CTC-501 to this point, and to my fellow Alto teammates and our shareholders for their continuous support. This concludes today's prepared remarks. Operator, we can now open the line for Q&A. At this time, if you would like to ask a question, press star, then the number one on your telephone keypad. To withdraw your question, simply press star one again. We ask that participants limit themselves to one question and return to the queue for any additional. We will pause for just a moment to compile the Q&A roster. Your first question comes from Paul Matteis with Stifel. Please go ahead. Hey, thanks so much for taking our question. This is Julianne for Paul. Really interesting presentation. I guess just on the data, on the asset itself. Can you confirm it's an eight-week single-blind study of 32 patients, right? Was that a single-site study, or how many sites were included in that? I guess just what gives you confidence that based on your diligence of the data that you'll be able to replicate the effect there in a small sample size? I guess one other quick follow-up is, I guess you're adding sort of a late-stage trial to your portfolio. You noted that the cash runway is not impacted. Are there other assets that you are deprioritizing, or how does the math work there? Thanks so much. Great. I will take the first question and then hand off to Nick on the financials. There is a single-site, multiple investigators, obviously a phase IIa study. You have to remember that not only that large effect size, something that was seen in that study, but echoed then what is seen in all of the other prior studies, and most notably in PAX-D, which was a nine-site, 150-person study of pramipexole when given alone. As Alan and Mike said, there is really a strong track record of efficacy for pramipexole. Obviously, the tolerability part as well, and that is what this is solving. That gives us a lot of confidence that we'll be able to get a similar signal in subsequent trials, obviously on a larger footprint than the phase IIa trial. I'll let Nick speak to the financial side. Yeah, thanks, Amit. Thanks for the question, Julian. One thing just quickly to add, right, on that prior study, the raters were actually blinded to the treatment. That's an important piece of it, right? I think that for us, it gives us a lot of confidence in the validity of that study. On the cash side, obviously, you've known our operations for a while now. We run pretty lean internally. We run our own clinical operations internally. We don't leverage external CROs broadly, but are able to execute in a way that is very capital efficient. This addition of this asset doesn't result in the deprioritization of any of our assets that are in the pipeline. As we mentioned, still achieving all of those milestones. We have implemented a few operational efficiencies, but things that were more around the edges here and allow us to get there with current cash as we were guiding into 2028 already previously, right? Really a great opportunity here to bring in a late-stage asset and develop that forward alongside the rest of the pipeline. Excellent. Thanks so much. Your next question comes from Myles Minter with William Blair. Please go ahead. Hey, congrats on the deal. Thanks for the questions. I've got two. One's just on the proposed titration schedule for ALTO-207. You said you'd achieve that sort of 5 mg per kg or thereabouts in 12 days. I think pramipexole was done 0.25 mg per kg, and it was up titrated every three days. Just maybe talk about the frequency of up titration we can expect there. The second one is just about the PAX-D data. I find it very intriguing. It's a question about functional unblinding and if patients knew they were on drugs because of the high rates of nausea and vomiting and if they were willing to push through. Maybe that's exacerbating the effect size there as we've seen in other neuropsych trials. We'd just love your opinions on that. Thanks very much. Yeah, thanks, Myles. I'll address the first question and then ask Mike to address the second question, and we have a supplemental slide that speaks directly to that. On the first question, the frequency of up titration, just to be really clear, that 0.25 every three days, that's what PAX-D did in following the FDA label. That's that slower titration. PAX-D targeted 2.5 mg over 28 days. This titration was far faster, and we continued to evolve that titration schedule to continue to kind of improve the tolerability profile of ALTO-207. What was done by Chase was up titrating to a target of 5 mg over just eight days. Obviously, much, much faster in that phase IIa. In total, there's a similar titration in the phase I and the phase IIa, which is about five times faster than the label. That's really what supports going to a higher dose and doing it faster with a potential rapid onset of efficacy that that achieves. In terms of the unblinding question, I'd like to invite Michael Browning to address that, and if we could show the slide that speaks to that. Great. Thank you very much, Amit. Hopefully, the slide's being shown. We measured unblinding in PAX-D at the end of the study. We asked people what they thought they were on and how confident they were. We asked them how they made their guess. The side effects did unblind people, but the other thing that obviously unblinded people in this study was the efficacy. People who felt better thought they were on active treatment. We looked at that in a post-hoc analysis that's shown in the slide. This is the week 12 data. It's the change in QIDS-SR from baseline to week 12. We basically split that up into the group of people on the left that thought they were on placebo, and then the group of people on the right, the right two bars, who thought they were on pramipexole. You can see they were then split up within each one as the ones that actually were on placebo and they actually were on pramipexole. What you can see is even keeping expectation constant, there was a benefit of pramipexole. There is a greater reduction in symptoms in the pramipexole group than the placebo group, regardless of the baseline expectation and effect of unblinding. It is quite an unusual analysis to do, and I think speaks to the sort of robust nature of the efficacy signal from this treatment. I'll hand it back to Amit now. Great. Thank you. Yeah, and to underline what Mike said, assessing what people thought they were on is actually quite rare in psychiatric trials. Obviously, it became a point of debate in the literature and in the field of late. Kudos to Mike and his team for doing that. It's very clear that efficacy is what drove this signal. Importantly, the tolerability further improves with ALTO-207 over pramipexole alone. Again, the focus is here on efficacy. Thanks for the question. Jump back in the queue. Your next question comes from Andrew Tsai with Jefferies. Please go ahead. Hey, good morning. Congrats on the deal. This is John on behalf of Andrew Tsai. I was just curious about the Chase study. Was this in a mono or adjunct setting? And then secondary to that, ultimately, what led you to pursue TRD instead of MDD, like any color that you can provide? And then maybe just one more if I can. Why is the study starting mid-2026? I guess, what are you guys hoping to accomplish in the meantime? Thanks. Yep. Thank you. This was a mono. The phase IIa was a monotherapy study. PAX-D, I should note, was an adjunctive study. For context, the reason we're going after TRD is multiple. As a commercial and clinical case, it's pretty much the highest need population to go after in depression. There is very strong data now across PAX-D as well as prior work showing efficacy in TRD, which is very rare. That allows us to go for the highest value population. Of course, over time, we would look to potentially expand the label from there, but really going for the most challenging and most in need population. The mid-2026 starting point for the phase IIb is really driven by the CMC work that's needed to prepare the clinical material for the trial. That just takes time, and we're going to gear up the clinical trial in the meantime, so it's a timely start for clinical activities. Great. Thanks so much. Your next question comes from Ritu Baral with TD Cowen. Please go ahead. Good morning, guys. Thanks for taking the question. One question on efficacy and one question on safety. Amit, what receptor occupancy range are you targeting? What's been investigated, and what dose do you think that, what sort of peak dose do you think that translates to in the trial in clinical development going forward? Was there a second question too, or do you want me to address the first? Oh, yeah. Yeah. Whatever you'd like. I can list the question now, or you can start on occupancy. Sure. Let me address the occupancy question. There's some PET data on pramipexole that really, because of just how titrating it and tolerability factor in, kind of bookends a bit. On the low end, around 0.25 mg-0.5 mg have been looked at, and then on the higher end, around 2 mg. In both cases, receptor occupancy is pretty low. It's maybe 10% at 0.25 mg-0.5 mg and maybe 30% at 2 mg. That suggests that there's a lot of room to go up. We'll say more about what the dosing is for our phase IIb when we get closer to launching it. That suggests that even at that equivalent dose, let's say, to a PAX-D study, and certainly at the dose achieved, the 4.1 mg by the Chase phase IIa study, you're at at least a 30% target occupancy where you ultimately want to hit. That's unknown because nobody's really been able to go high enough to be able to test that. We'll say more about the dosing component when we get closer to launching the phase IIb study. Got it. Is that part of the IP strategy, the occupancy and dosing? Yeah. Dosing is certainly part of the IP strategy. I mean, part of the goal here is, of course, achieving a dose that you can tolerate both faster and higher. And that's something unique to the combination. Got it. On the safety side, has there been any, just given the mechanism, any drug liking studies around this done? And what were those data? Otherwise, what are you planning on doing around that, and what might agency requirements be? Yeah. You have to remember this is an approved drug for Parkinson's disease. A lot of people have gotten it in that context for many years. There's really not been any evidence. You do not have to even look at drug liking assays. You can actually just look at any kind of dependency behavior. There's not really been issues in the past. In fact, there's even some discussion of whether it's a treatment for addiction. There's a really, really strong safety base there in terms of pramipexole and its long-term use. There's also safety information on ondansetron. It's actually labeled only for three days, but the tox covers chronic use. We would be expanding the horizon, certainly in going from three days to chronic use in humans of that drug. All of this is, of course, wrapped into our IP, where we have a strong IP position, starting with the composition of the combination itself, plus various aspects of its use that takes us well into the 2040s. Got it. The aspect of impulse control and impulse control exclusion, is that something that sort of extends into, say, OCD or comorbid OCD? How much of the TRD population does that impact? That is not a significant portion of the TRD population. The concern here, as Mike was outlining, was more around the historical and kind of observational data in Parkinson's disease, which suggests that when you give pramipexole for some people, itt creates an increased likelihood of impulse control disorders. That does not appear to be the case from a variety of sources on depression trials that includes the PAX-D study. That may very well be more around the pathophysiology of Parkinson's itself rather than pramipexole as a treatment. We do not think that is going to be a significant concern in depression. Understood. Thanks for the color. Your next question comes from Patrick Tru with H.C. Wainwright. Please go ahead. Thanks. Good morning. Just a few questions from us. I am just curious, is the antidepressant activity of ALTO-207 hypothesized to be purely dopaminergic, or do you believe serotonergic modulation from ondansetron may contribute directly to the efficacy? Then separately, I was wondering in the phase 2IIb program, do you intend to include biomarker-negative patients in the phase IIb trial to validate that specificity of response? Lastly, just as we're thinking about the phase IIb program and the potential for this to be registrational, I'm just wondering, I guess, what elements of this design, the duration, primary endpoint, patient selection, could position it for registrational status? Have you begun to have those discussions with the FDA? Yeah. On the first question, our understanding, and certainly the data thus far, suggests that it's primarily a dopaminergic mechanism. We do not think that the 5-HT3 antagonism of ondansetron contributes to that. Dopamine itself will have secondary effects on serotonergic and other signaling, but really, it's primarily the direct dopamine action that drives the therapeutic effect, and especially the unique D3-preferring aspect of pramipexole, which you don't see in other D3/ D2 agonists. The second question about including biomarker-negative patients, we're looking here for a broad TRD label. We will be including the whole population of TRD patients in the phase IIb trial. Then secondarily, as key secondary analyses, pre-specifying biomarkers, which will then get confirmed again in a broad trial in phase III. What that means is we will be including biomarker-positive and negative as part of that broad population. We will be able to look at the benefit, the additional benefit that a biomarker gives. In terms of the registrational elements of the trial, everything you mentioned is part of it. The population, the duration, primary endpoint are all, as one would expect for a TRD study. This is something that we'll be talking further with the FDA. We obviously just acquired the compound, so we're building on Chase's interactions with FDA, but we'll be additionally having interactions ourselves. There is a progressive clarity there that gets achieved every time you interact with them. All of that will be happening before the phase IIb launches, and will directly inform the phase IIb. Great. Thank you so much. Your next question comes from Justin Walsh with Jones Trading. Please go ahead. For taking the questions. I guess, given the size of the effect observed with ALTO-207 so far, if you expect the EEG patient selection is necessary and, I guess, worth the effort of inclusion. And then the quick follow-up on this. I'm wondering if you can discuss a little bit about potential overlap in your target populations across your depression-focused assets. Yep. On the first question, again, we're going for a broad TRD label, right? The biomarker here, think of it as more like an enrichment or complementary biomarker. It's the kind of thing that, if you're faced with several treatment options, may help push you to this treatment option in particular for TRD. It also, as Mike Browning was saying, and I highlighted later, is not just about efficacy. It's also about tolerability. If we knew that you have no problem tolerating this and therefore this might actually be ALTO-207, might be a really preferred choice, that would certainly be useful. That biomarker may not be EEG. As I noted, things like reward-based learning, which is based on a web-based behavioral task like we've been doing in other contexts, could be another way to assess dopaminergic function. We have several other such tasks that we'll be employing. We will be looking at all those different aspects of behavior and EEG, but ultimately, our bias is towards scaling the thing that's easiest, especially in a context like this where it's a complementary diagnostic that just helps gain that much more confidence that it is the right path for that patient. Obviously, very excited about the effect size that we see. In terms of potential overlap between the different assets and their mechanism, if we can go to slide 11, that shows the kind of commonality between our dopaminergic anchored or dopaminergic inclusive mechanisms, but also their differentiation. The way we think about this is, for example, ALTO-300 as an adjunctive treatment in depression. Some of those patients will be TRD in that trial. There is certainly some overlap there in terms of the broad clinical population. These drugs do different things. The profile for ALTO-300 is an extremely well-tolerated drug that also has circadian and sleep effects by virtue of the melatonergic signaling. There is some overlap, and that is intentional because it harnesses our mechanistic understanding, as we talked about from a biomarker perspective, but they treat different aspects of biology and really different profiles clinically, even if they anchor in elements of dopaminergic control. Your next question comes from Laura Chico with Wedbush Securities. Please go ahead. Hey, good morning. Thank you very much for taking the questions. I have three quick ones. First, strategic. Could you talk about the timing of the acquisition? I guess, why does it make sense right now to expand your asset footprint? Second, could you talk also about the selection of the immediate-release formulation versus the extended-release formulation of pramipexole? Just curious about the rationale and why one would make more sense than the other. Lastly, I think this might actually be one question for the physicians, Dr. Browning and Dr. Schatzberg. I'm curious, in your experience, has there been any hesitation to prescribing an antiemetic with pramipexole at present? I'd love to hear a little bit more. If so, what have been some of the limitations on co-prescribing those agents? Thank you. Great. Let me address the formulation question first, hand off to Nick to talk about the timing of the acquisition, and then invite Mike and Alan to comment on the antiemetic. The use of the immediate-release historically has been what's been done in studies of depression. PAX-D was an immediate-release formulation of pramipexole, kind of in its simplest terms, with something that has, if you will, on-target but off-brain region effects on things like emesis. Immediate-release will achieve a higher Cmax, which will end up having higher side effects. There is certainly benefit from an extended-release conceptually, but that just hasn't been included in trials in the past. We'll say more about the release profile and the kind of approach there for the phase IIb trial as that gets nearer. In terms of the timing of acquisition, let me hand off to Nick to address that, and then from there to Mike and Alan on the antiemetic. Great. Great. Thanks for the question, Laura. Certainly, this has always been a part of our strategy as a company is evaluating different assets that have clinical validation and also offer differentiated effects in patient populations where we think our biomarker platform can be of utility. The timing on this one is based on the fact that over the past year, we've really, as Amit mentioned, really gone through a lot on the dopamine biomarker side. As we looked at the way in which we're approaching dopamine, we really thought about this from the perspective of what other potential approaches could there be. That direct dopamine agonism was really one that we wanted to corner. When we went out to find a good direct dopamine agonist, this was, to us, the best available option that we thought makes a whole lot of sense here and also provides a much shorter path to commercialization, right? I think we can see the clear examples and the utility of combining an effective agent with an agent that also mitigates side effects through Cobenfy and Auvelity. We have clear commercial cases here for success with the approach. To us, makes a lot of sense regardless of timing. Obviously, you can't always pick your timing on some of these strategic things that you look at, but for us, this one made a lot of sense right now. Let me then hand it off to Alan to address the question on any hesitation historically in using antiemetics. Can you hear me? Yep. Okay. It's a very, very good question. In general, we have not had to use antiemetics commonly until the use of intravenous ketamine, where we often will use something like ondansetron when we're using IV ketamine. In general, the SSRIs, when they first came out, had some nausea, but in general, it was just really dose-related, and people worked around it. In terms of using antiemetics, it is not terribly common other than, I would say, ketamine. With the pramipexole, I do not think people thought of it that it would be a good idea. Remember, there are two things to keep in mind with the antiemetics. One common antiemetic, actually, are the dopamine antagonists, which if you look at Compazine, for example, which you would not particularly want to necessarily mix with pramipexole as a dopamine agonist. That would be one. The other would be the 5-HT3 antagonist commonly, like ondansetron. I don't think people would have thought that necessarily a 5-HT3 antagonist would block the emetic effects of a D1 agonist. I just don't think, I think it's a novel. I think that's what led to this novel IP that Chase Therapeutics came up with. Just to kind of put a finer point, right, that is the innovation here is that a big part of the limitation in the past has been the slow titration needed in order to avoid nausea and vomiting, which we still get in a substantial portion of people, which Michael Browning showed in the PAX-D study, at least a 20% dropout. It's really understanding what the mechanisms of that are. This unique IP-protected combination with ondansetron exactly as Alan had illustrated, which is surprising and novel, shows great efficacy. That allows you to harness that information to be able to dose faster and higher than had been, I mean, clearly faster than is possible with the traditional form. The time it took for the folks to reach 2.3 mg, which is the ultimate dose for PAX-D with a target of 2.5, is still well, well shy of the 4.1 mg reached by the Chase phase IIa study. All of that requires, as Alan also highlighted, a lot of hands-on titration, calls from patients who are getting side effects and so forth. Frankly, as a clinician, especially as a psychiatrist, having people vomit is sort of a non-starter for treatment. Most clinicians are really not prepared for that. That all supports the novelty and the power of having this co-formulation. I think when you're prosecuting patents, obviously, one of the big limitations in terms of obtaining patents is the question of obviousness. Interestingly, it's not particularly obvious, although in retrospect, it seems like a pretty good idea. I mean, that's what makes it an invention. Thank you, guys. There are no further questions at this time. I will now turn the call back over to Amit Etkin for closing remarks. Great. Thank you, operator. Thank you all for joining this investor conference call to discuss the exciting acquisition of this novel, the dopamine agonist combination candidate. We appreciate your continued interest in Alto, and we look forward to updating you on our progress. Thank you. Ladies and gentlemen, this concludes today's call. Thank you all for joining. You may now disconnect.