Good morning and welcome to the Ovid Therapeutics Data Call. At this time, all participants are in a listen-only mode. A Q&A session will follow the formal presentation. If you'd like to submit a question, you may do so by using the Q&A text box below the webcast player. As a reminder, this call is being recorded, and a replay will be made available on the Ovid Therapeutics website following the conclusion of the event. I'd now like to turn the call over to your host, Victoria Fort, Senior Vice President of Corporate Affairs and Corporate Strategy. Please go ahead. Thank you and welcome. Good morning, everyone, and thank you for joining today's call to discuss the Topline OV329 phase I readout. Joining me on today's call are Dr. Jeremy Levin, Chairman and Chief Executive Officer of Ovid; Meg Alexander, President and Chief Operating Officer; Jeff Rona, Chief Business and Financial Officer; and Zhong Zhong, Chief Scientific Officer. As a reminder, during today's remarks we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for the purpose of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Forward-looking statements contained in this call are subject to a number of risks and uncertainties, which could cause our actual results to differ materially from those expressed or implied in such statements. These factors include, but are not limited to, those discussed in our most recent annual report on Form 10-K and other filings with the Securities and Exchange Commission. Dr. Levin will provide an overview of Ovid Therapeutics, and Meg Alexander will walk listeners through the OV329 topline phase I biomarker and safety data. We will encourage Q&A after the presentation. With that in mind, I will turn the call over to Dr. Jeremy Levin. Thank you, Tori. I'd like to welcome everyone to the webcast. We're incredibly excited to share our phase I OV329 data with you. Before we dive into that data, I would like to provide our listeners with an overview of Ovid's pipeline, discuss the significant unmet need in epilepsy, and the challenges with current GABA-modulating medicines. I will then turn over the presentation to Meg to provide detailed phase I results for OV329. Ovid's focus is threefold. First, we're drugging fundamental biological targets implicated in conditions driven by neural hyperexcitability and which have broad potential therapeutic utility. Second, we are developing a pipeline of highly specific small molecules with the intention of creating a fully integrated neurotherapeutics company, and third, our candidates have been differentiated mechanisms of action from the growing field of me-too medicines. It's our belief that in three to five years, we will see mechanistic category winners, and novel compounds and modes of action will be highly valuable, especially if they're well tolerated and efficacious. In front of you now is our focus neurology pipeline, which encompasses OV329 for treatment-resistant epilepsies and focal onset seizures, and our portfolio of potassium chloride co-transporter 2, or KCC2, direct activators. Our pipeline is highly differentiated, pursuing novel mechanisms in the CNS. If you look at the right-hand column of this slide, it highlights the numerous clinical and regulatory catalysts that we expect to achieve between now and mid-2027. Now, let's start with OV329, our next-generation GABA aminotransferase, or GABA-AT inhibitor. Now that we've successfully completed the phase I safety and biomarker strategy, we anticipate initiating a phase II-A in Q2 2026, followed by top-line data in mid-2027. We will simultaneously conduct a small open-label seizure reduction study to demonstrate anti-convulsant properties. Our portfolio of KCC2 direct activators has also made significant progress. This portfolio includes OV350, an IV KCC2 direct activator, which is currently being studied with the objective of demonstrating safety, tolerability, and PK for a first-in-human MOA in the CNS. The OV350 phase I was initiated earlier this year, and we expect a readout of top-line safety, tolerability, and PK data in Q4 2025. It will provide rich insights into our oral programs. Excitingly, the first oral direct activator, OV4071, is currently completing the final pieces of our IND-enabling package, which we will submit early in 2026. This will support a phase I, 1b set of studies that will initiate in Q2 2026. For OV4071, while we characterize safety, tolerability, PK, and exposure in our phase I, we plan to conduct a proof-of-mechanism study in a ketamine challenge, which may significantly de-risk future studies in schizophrenia. In late 2026, we will initiate 1b studies in psychoses associated with Parkinson's disease, dementia, and Lewy body dementia, and separately schizophrenia, with the goal of delivering early proof-of-concept data in Q1 2027. As we do this, it's important to take account of the need in treatment-resistant epilepsies. Despite 30 anti-seizure medications being approved over the last 15 years, only two with novel mechanisms have been authorized, leaving a significant unmet need. Even in a crowded epilepsy landscape, one in three patients live with uncontrolled seizures, and 47% of U.S. epilepsy patients report polypharmacy with an average of five medicines. A safe, well-tolerated GABA aminotransferase inhibitor is clearly needed. The next slide that you see before you highlights the challenge with current GABA-modulating medicines. The first-generation GABA-AT inhibitor, vigabatrin, has a challenging safety profile with irreversible retinal changes and vision loss in some patients. Dosing isn't patient-friendly, requiring two to three grams of drug. Even drugs that work well in reducing seizures have tolerability issues. Specifically, drugs that surge GABA in the synapse have been associated with high instances of sedation and dizziness, and other GABA-modulating drugs have limited durability of effect. Those are the challenges we took on and are tackling. I'll now turn the call over to Meg Alexander to discuss the top-line phase I biomarker and safety data for OV329. Thanks, Jeremy. This is a really exciting day for us. As you can see in front of you on slide 10, based on our phase I and preclinical results, we believe OV329 has the potential to make an important impact on the treatment of drug-resistant epilepsies and potentially deliver a superlative safety and efficacy profile relative to the broader category of anti-seizure medicines. The results that we're going to describe today demonstrate a positive safety profile relative to a broad and historical category of anti-seizure medicines. Of course, this includes clean ophthalmic safety results. You will see that we showed positive biomarker data across a range of metrics which support that our medicine engages and inhibits the GABA aminotransferase enzyme. The inhibitory effects of 329 are on par or in excess of the first generation of GABA-AT inhibitors like vigabatrin, as Jeremy described. We observed in our results a clear responder rate such that we know that we are having inhibition at the modeled drug exposure levels in the brain, as we had predicted. And we believe that OV329 has the potential to be a blockbuster, and we have patent protection through 2041 with the opportunity for patent term extension as well as future IP. So we strongly believe that the data we're going to show you today rapidly support advancing OV329 into a phase II-A patient epilepsy trial. But first, let's take a moment to stop and discuss the mechanistic and therapeutic index differences that we've characterized and that are associated with OV329. So as we introduced at the top, OV329 is a next-generation GABA aminotransferase inhibitor. And that means that essentially our drug is inhibiting the enzyme that degrades the main neurotransmitter in the brain, GABA. Unlike other drugs, vigabatrin, most particularly like vigabatrin, OV329 is unique in that it delivers GABA both in the synapse and in the extra-synaptic, and in this way, OV329 is delivering what we call phasic and tonic inhibition. By optimally tuning GABA levels in the brain, OV329 is creating an overall inhibitory environment surrounding the neurons. Therefore, OV329 has a therapeutic index that can deliver this phasic and tonic inhibition where the prior-generation medicine vigabatrin cannot, but why does all this matter? It matters because the phasic and tonic inhibition may deliver a preferable tolerability and efficacy profile relative to prior anti-seizure medicines that primarily surged GABA in the synapse and led to tolerability challenges, and the robust efficacy profile that we've now observed in humans really set the stage in earlier preclinical models where we saw a lack of accumulation in the eye differentiating from vigabatrin. Also, we saw strong anti-seizure efficacy that supported advancing OV329 into the clinic. Specifically, OV329 was studied and shown to have anticonvulsant properties in nine chronic and acute seizure models. This is perhaps more than what we have seen for any prior anti-seizure medicine. On the left-hand side of the slide, you'll see that plasma and tissue exposures for OV329 differ substantially from vigabatrin in a mouse model intended to look at ophthalmic safety. Importantly, we have proven that vigabatrin, the first-generation medicine, preferentially and idiosyncratically partitions and accumulates in the retina rapidly. In fact, we've been able to see this in animals within days and even weeks. Whereas for OV329, in the brain, eyeball, and retina, we know that our therapeutic doses are undetectable. We get into the plasma and tissue and clear it rapidly. This makes us very comfortable that OV329 has a differentiated ocular and ophthalmic safety profile where we do not anticipate the vision issues that were experienced by the first-generation vigabatrin. So as we think about the future of what this medicine could be, we designed OV329 with a target profile to address the challenges that Jeremy elucidated a few moments ago about prior GABA-acting medicines. At this point, we know with OV329 that we are quelling hyperexcited neurons and optimally tuning that synaptic and extra-synaptic GABAergic inhibition. OV329 is delivering cortical inhibition that we've measured now in humans that either matches or exceeds what we've seen of therapeutic doses of vigabatrin also studied in healthy volunteers. And this gives us incredible conviction about the anti-convulsant and anti-seizure efficacy that OV329 may deliver. We anticipate that 329 will be given once daily at significantly lower doses than vigabatrin. Our dosing estimate for patients is five to seven milligrams versus two to three grams for vigabatrin. Significant difference. 329 has a superlative safety profile, not just compared to vigabatrin, but really even as we look at the entire class of anti-seizure medicines. And of course, none of the vision changes are expected that are unique to vigabatrin. This means that we do not anticipate further ocular monitoring. We expect to see sustained focal reduction or sustained reduction, rather, in focal seizures with no intended titration. And with this overall target product profile, we believe OV329 is poised to serve a broad population of people living with treatment-resistant focal onset seizures, as well as other disorders where neural excitation is implicated. So let us get on to telling you about the results. What we're showing here is the trial scheme for the phase I SAD/MAD study that we just recently completed for OV329 in healthy volunteers. We had 69 participants who were enrolled. 51 of those were receiving active treatment. The largest cohort in our study was our five-milligram cohort. That included 15 participants who were receiving actively the medicine and five who were receiving placebo. Importantly, we had several objectives for this study, one of which was measuring ophthalmic safety and tolerability, which included a number of very rigorous metrics such as best-corrected visual acuity, fundus photography, indirect dilated ophthalmoscopy, automated threshold visual field perimetry, and optical coherence tomography. These were very rigorous methods that measured not just clinical effects, but even the back of the eye for changes. In addition, we leveraged the following technologies to look at pharmacodynamic activity for OV329. These are predictive biomarkers specifically that we leveraged technologies such as transcranial magnetic stimulation, or going forward, we'll refer to this as TMS, magnetic resonance spectroscopy, or MRS, and electroencephalography, which is EEG. So here, we'll quickly hit on patient demographics. You'll see they were well-balanced across our MAD cohorts, and there were no significant differences in gender, age, height, weight, or body mass index. But let's get right into the results, starting with safety. We're very pleased to report that OV329 demonstrated a very favorable safety and tolerability profile with no treatment-related serious adverse events. In fact, only three participants experienced treatment-related adverse events, all of which were graded as mild, all of which were transient and resolved. These included in our two-milligram cohort, one account of headache and one account of drowsiness. And on our five-milligram cohort, one incidence of metallic taste. The most frequent adverse event was actually cannula site reactions at the site of lab and blood draws, which 13 participants experienced. Of course, all of those were mild and moderate and not related to OV329. Importantly, as we expected, OV329 demonstrated a clean ocular safety profile with no ophthalmic safety findings or retinal changes in the five measures we applied in the study. As we know, this includes the best-corrected visual acuity, the fundus photography, indirect dilated ophthalmoscopy, automated threshold visual field perimetry, and OCT. These are very rigorous metrics and will continue to conduct similar ophthalmic studies throughout the entirety of OV329's development, and the reason why is beyond the preclinical de-risking work that we have already done, we want to build a robust human and patient safety database that will ultimately support our registrational package. Our goal, as you recall, is to mitigate the monitoring that people who took vigabatrin are required to adhere to. Let's talk about how we are seeing OV329's PK and PD performance behave. In the phase I study, OV329's irreversible binding and incredible potency, coupled with the low turnover rate of the GABA aminotransferase enzyme in the brain, enabled low daily dosing and delivered a prolonged pharmacodynamic effect. We observed linear increases in AUC and Cmax using repeat dosing and achieving steady state by day three. We also had consistent renal clearance, which was observed after single and repeat dosing. We know at very low potent doses, we're able to leverage the slow turnover of the enzyme and maintain our pharmacodynamic activity. Now let's shift to the really fun part, which is the biomarker results for this study. As mentioned, we used TMS, which is a well-accepted technology for measuring GABAergic drugs using a range of very specific biomarkers, most particularly that evaluate changes in cortical inhibition. Specifically, we looked at the long-interval intracortical inhibition, or the LICI, and the cortical silent period, or CSP for short. These two biomarkers are pure quantitative measures of cortical inhibition, and they provide an optimal way of measuring GABAergic inhibitory activity short of an actual seizure reduction trial. We utilize these biomarkers in both our three and five-milligram cohorts where we anticipated to see pharmacodynamic activity. And whenever we could, we compared them to therapeutic doses of vigabatrin, as had been previously studied in healthy volunteers. Based on the results, we believe OV329 has delivered more confirmatory evidence of inhibition in the brain than any prior seizure medicine that we have seen at this stage of development. On the two measures that vigabatrin historically demonstrated an effect on TMS, which were the long-interval intracortical inhibition at 150 milliseconds, or the LICI, and the cortical silent period, OV329 delivered greater inhibition while acknowledging, of course, that these are still cross-trial comparisons which must be taken into account. Importantly, OV329 replicated the signature fingerprint on TMS that's been associated not just with vigabatrin, but with a broader GABA aminotransferase inhibition mechanism. Specifically, we saw the greatest inhibition for OV329 was delivered at approximately 150 milliseconds on this LICI, which is a paired pulse biomarker, and we see that inhibition diminish at 200 milliseconds. Why does that matter? It's measuring millisecond-level reactions of inhibition in your brain, and importantly, it replicates and exceeds therapeutic doses of vigabatrin, so let's talk just about the methodology for how we measure this. We'll start by talking about the LICI, which again is a measure of cortical activity, and it uses two separate high-intensity stimuli, or paired pulses, that come in intervals. A magnetic coil is placed on the volunteer's head to measure an electric field, and electrodes are placed on target muscles to measure motor response. This paired pulse stimuli are then delivered at varying time intervals to obtain levels of GABA-mediated inhibition. The mean responses to measure were pretreatment, so we measured before any participants were dosed with our medicine on day one. And then we measured again after seven days of daily dosing. We'll take a moment now to show you the results from our five-milligram cohort. At five milligrams of OV329, we demonstrated a highly significant improvement in the LICI measured at 150 milliseconds as compared to placebo. We measured that on day seven in the APB muscle, which stands for the abductor pollicis brevis muscle. You can see that 53% inhibition compares very favorably to the approximately 35% inhibition that had previously been determined for a therapeutic dose of vigabatrin as dosed at 50 mg per kg in a study by Pierantozzi et al. In another muscle that we measured this biomarker in, the first dorsal interosseous, at the 5-milligram dose of OV329, we also demonstrated highly significant improvements in the LICI measured at 150 milliseconds compared to placebo on day seven. You can see here the 44% inhibition compares favorably to the approximate 35% inhibition of vigabatrin. In both of these biomarker metrics, you can see that our p-value is highly significant. As you can see, each of these biomarkers were measured in two different muscle groups, delivering highly confirmatory results of the signal and the inhibition that we're seeing with OV329. What you're seeing in front of you on this slide, slide 25, illustrates how OV329 compares to vigabatrin's performance on this particular biomarker, the LICI measured at 150 milliseconds. These results were measured in the FDI, or first dorsal interosseous muscle. You can see, as you look at this slide, the dotted green line is essentially showing where vigabatrin delivered its most profound inhibition, roughly between 140 and 160 milliseconds on the paired pulse stimuli. We set OV329 to see if we could achieve inhibition at the similar paired pulse time range. Indeed, OV329 did. It delivered more inhibition, which is suggested here by the square at the bottom. That's the difference in inhibition relative to the pre-drug baseline at the top. As you can see, OV329 delivered cortical inhibition of approximately 53%, surpassing that seen from vigabatrin. Moving along, we saw similar results on other muscles as well. The cortical silent period is another biomarker that had been used to study cortical inhibition. It's described here on this slide. This particular biomarker uses muscle exertion and the stimuli on TMS to measure cortical activity. What we want to see when you have an inhibitory drug on board is treatment-related prolongation of this cortical silent period. That's indicative of GABAergic activity. If you look at the right, that's the metric of someone who has a reading of the cortical silent period without an inhibitory drug. If you look on the bottom right, you'll see prolongation of the cortical silent period that's indicative of a drug that's having an inhibitory or GABAergic effect. So now let's take a look at the results. On the cortical silent period, our five-milligram dose of OV329 had highly significant prolongation of more than 10.4% at day seven compared to the participants' pretreatment baselines, whereas placebo showed a non-significant improvement of 2.5%. So we've been quite pleased with the biomarkers that we've now seen using TMS. We've replicated the results, not just that vigabatrin achieved, but also what OV329 has achieved across multiple muscle groups in highly statistically significant fashion. So now let's move on to some of the other biomarkers that we also measured. On magnetic resonance spectroscopy, our results are highlighted here. Magnetic resonance spectroscopy showed the signs of drug effect and target engagement for OV329 based on an observed change of GABA concentration in the brain. We measured and looked for signs of GABA in the medial parietal lobe within 24 hours of the last day of dosing OV329, so on day seven. We measured that relative to our participants' pretreated baselines. In the results, we observed numerical increases in both doses of OV329 relative to placebo. While the results were not statistically significant due to variability and baseline variability in the participants, regardless, we saw a clear separation from the placebo subjects and an elevation of GABA in the brain. Putting this together, the results suggest that OV329 is getting into the brain, inhibiting the GABA aminotransferase enzyme, and importantly, increasing GABA levels in the medial parietal lobe as was studied. And finally, the last technology that we applied in this comprehensive biomarker program was EEG. It's important to understand that EEG methodology is just a more exploratory area of the field, though the results that we saw, excitingly, were also supportive of having a dampening effect relative to excitation in the brain. Specifically for OV329, we saw statistically significant increases in beta, delta, gamma, and theta power. We saw this both in the three and five-milligram doses of OV329, while placebo showed statistically significant reduction in beta power. These tend to be reflective of GABAergic activity and may indicate some signs for some of these brain wave bands, signs of drowsiness, though there were no reports of drowsiness in our high-dose cohorts from our drugged participants. Finally, and really importantly, as drug developers, we measured exposure of OV329 in the brain and found that it was highly correlated to inhibition. This is demonstrating in front of you a clear responder rate. Essentially, what it's showing you is that patients who achieved the target exposure threshold in the brain of approximately or greater than 80 nanograms per hour per ml were highly correlated with cortical inhibition as measured by the biomarker, the LICI, 150 milliseconds. And you can see that reflective of the blue circles in the lower right-hand circle of this pictorial, which is showcasing that at our five-milligram cohort, we are delivering drug exposure in the brain as predicted. And simultaneously, that is delivering highly significant inhibition. So we're extremely pleased with these phase I results. They showed positive and potentially best in therapeutic area safety. And that profile is, of course, recognizing that our AEs were mild, transient, and of course, we didn't anticipate, nor did we see any concerns of ocular safety. So we can firmly say that we've demonstrated that OV329 is crossing the blood-brain barrier and engaging and inhibiting the GABA aminotransferase enzyme. We are exhibiting similar or better inhibitory effects of therapeutic doses of vigabatrin, which is incredibly encouraging for what the possible anticonvulsant efficacy of OV329 may deliver. Patients and participants who achieved target drug exposures in the brain of approximately 80 nanograms per hour per ml or greater saw cortical inhibition as measured by the LICI 150. This is demonstrating a clear responder rate that will help us make decisions for dosing and powering as we move into phase II patient studies. And the results very much support advancing OV329 into phase II- A seizure and epilepsy trials. And where we will go first is patients who are experiencing treatment-resistant focal onset seizures. So let's tell you about what's coming next. In front of you, you're seeing our proposed phase II-A trial design in treatment-resistant focal onset epilepsies and seizures. It is our intention to evaluate a seven-milligram dose of OV329 as compared to placebo for eight weeks in a two-to-one randomization. Patients with diagnosed treatment refractory focal aware and focal awareness impaired motor onset seizures with zero to three concomitant anti-seizure medicines will be enrolled. The efficacy outcome measures will include percent change from baseline in monthly seizure frequency, responder rate, times of pre-randomized monthly baseline seizure frequency, seizure-free days, and of course, clinical global impressions of improvements among caregivers. These are very traditional epilepsy metrics that will help us assess the full utility of OV329. We'll also run a concurrent open-label cohort to be able to potentially get a readout of seizure effect size and reduction sooner than this phase II-A placebo-controlled trial that we're showing you here. In terms of the market opportunity, we believe that OV329 can deliver a highly differentiated, efficacious, and well-tolerated profile, which will be rewarded in epilepsy, even in spite of it being a dense and competitive market. In fact, the refractory and polypharmacy market in epilepsy and focal onset seizures represents approximately 40% of epilepsy patients and more than a $1 billion commercial opportunity. Reimbursement and coverage dynamics remain quite favorable in this space. And unfortunately for patients today, polypharmacy remains to be the norm and remains to be heavily covered and reimbursed. So with the financing that was concurrently announced today, our company has sufficient resources to be able to fund development of our programs and our company through 2028, during which time we'll initiate the following milestones and programs that you see in front of you. We intend to initiate a phase II-A program for OV329, similar to the design that I just showed you. And we expect to have top-line proof of concept data reading out by the middle of 2027. For our KCC2 program, we expect to read out safety, tolerability, and pharmacokinetic information about our intravenous KCC2 direct activator, OV350. And we'll do that later this year before the close of 2025. We think this is very important. It's the first time anyone has drugged and directly activated KCC2 in the brains of humans. And there's much we'll learn from this for our oral KCC2 development programs. From there, we intend to initiate a phase I and 1b study for, excitingly, the first-ever oral KCC2 direct activator, which, as you heard Jeremy describe, is OV4071. That's scheduled for regulatory submission early next year and initiation of the phase I program in the second quarter of 2026. During the time that we're running our phase I study, we will concurrently run what's considered to be a proof of mechanism ketamine study challenge, which will help us potentially de-risk future development and indications such as schizophrenia. We anticipate running two 1b studies near the end of our phase I, and that will be to explore OV4071 and indications that include psychoses associated with Parkinson's disease and Lewy body dementia, as well as schizophrenia. What will all of this get us? It will essentially get us proof of concept-like readouts in early Q1 2027. Then finally, we have additional KCC2 molecules that we continue to characterize and develop. So in this period of time, we'll initiate IND enabling studies for the second and the next generation oral compounds in our KCC2 portfolio. We'll do that in late 2025, and we anticipate regulatory and IND submissions for that second oral, OV4041, by the second half of 2026. So now, thank you for sharing this exciting moment and the results with us. We'll conclude the presentation part of this discussion, and we'll open the floor to Tori and open it to Q&A. Thanks, Meg. Operators, please open the line for Q&A. Thank you, Victoria. At this time, we will begin our Q&A session. As a reminder, if you'd like to submit a question, you may use the Q&A text box below the webcast player. To our analysts, please raise your hand to indicate you would like to join the queue. With that, our first question comes from Laura Chico at Wedbush. Good morning. Thanks very much for taking the question. Just two for me. With respect to the phase II-A readout, has the bar for seizure reductions increased in the refractory focal population? We've seen some recent readouts there. So just curious, as you're heading into the phase II-A, how should we think about the bar for success for OV329? And then second, given the safety tolerability profile, I think it certainly makes sense to explore a 7 mg dose, but wondering what additional data you might have to support that. Thank you very much. Hey, Laura, good morning. Thank you for the very thoughtful questions. So this is Meg. I'll tackle the first one, and then we'll go into the second. So your question is, is the bar getting higher for seizure reduction in focal onset seizures? And I think the answer is yes. There are very good mechanisms out there, and there's development programs and existing medicines that seemingly do a pretty good job of reducing focal onset seizures. What is important to us as we look at this and as we project out where we think the field will be in three to five years, we think that there will be essentially mechanistic category winners. And what we mean by that is there's some good sodium channel drugs out there. There's some good potassium channel drugs out there, but there's also many in development. So we think eventually you will get a mechanistic category winner there. And what will be really important to bring to the field is having differentiated mechanisms of action beyond that. As Jeremy said in the presentation, there's only been two new MOAs been brought to epilepsy in the last 30 years. GABA aminotransferase inhibition and OV329 are that. So based on the data that we now have in hand, we believe that we'll bring to bear to the marketplace a differentiated mechanism that's safe, that's well tolerated, that has competitive efficacy, that should be on track with what we expect to see from vigabatrin and potentially better than what we saw with vigabatrin based on the inhibition that we're delivering and based on that phasic and tonic inhibition that 329 has. So when we look out at the field, we think we will have competitive efficacy from a seizure reduction perspective. So far, it appears that we may be having a safety profile that looks better than just about any other seizure medicine we've seen marketed or in development. So that's the answer to question one. Just on the 70-mg dose, I guess any additional data that gives you confidence there? Thank you. Yeah, yeah. So on the 70-mg dose, Laura, the way that we look at this is a couple different fold. Of course, first, the safety profile that we have at the five-milligram dose has really been superb. So we feel very comfortable being able to updose based on the safety data that we've seen in humans. But the other important string of evidence has really been developed by my colleague Zhong Zhong, who's sitting next to me. What we've done is we've used animal-based modeling. We've used enzyme-based modeling, vigabatrin, historic performance, as well as our own human PK and exposure data from our clinical trial to be able to model what should be therapeutic drug exposure levels in the plasma. We have that. That very much guided the dosing paradigm that you've already seen in the clinic between the three- and five-milligram dose. We knew with the five-milligram dose that we had exposure levels that were well, well within our modeling for pharmacodynamic effect and inhibition. The seven-milligram dose is on the far right-hand side of that continuum. So we don't want to leave any efficacy on the table. We think the seven-milligram may get us a little bit more, and we feel extremely comforted by the safety that we see today. Thank you. Sure. Thank you for the questions, Laura. The next question comes from Ritu Baral at TD Cowen. Good morning, guys. Hi, Meg. Thanks for taking the questions. So back to seizure reduction, can you give us any more detail about this open-label seizure reduction study that you guys are thinking about? Will it similarly have no titration? And as we put all of this biomarker data together and how you guys have compared it to the vigabatrin, what sort of level of seizure reduction is that pointing to in this open label? And then I have a follow-up. Very good. So in terms of how to think about the phase II design, we're trying to get really the best of both worlds here and robustly explore OV329. So what we mean by that is we feel it's very important to have a placebo-controlled phase II-A program. With OV329, while our inhibition is looking exceptional and the safety is looking exceptional, at the end of the day, we always know that we have to be able to differentiate from vigabatrin and the ophthalmic safety that we believe we have and that vigabatrin does not. So having a placebo-controlled trial is important to us. Nevertheless, we would like to be able to demonstrate the seizure reduction efficacy for OV329 sooner. So knowing that the placebo control is important, we are going to concurrently run an open-label study of OV329. While that doesn't necessarily give us placebo-controlled safety, what it does give us is seizure effect size. We think this will be important to enrollment, and it will be also helpful as we look at our modeling assumptions for the pivotal programs. What are the assumptions for top-line data from that open label? In terms of the seizure reduction, which is what I think you've got into Ritu, and that's similar to the question that you asked before. So we know vigabatrin has very compelling seizure reduction in focal onset seizures, as well as other indications of which focal seizures are a symptom. Depending on the studies you look at, we have seen seizure reduction anywhere in the range of 40%-60% to 35%-50%, depending on the indications. So keep in mind, Ritu, the one thing that we have that vigabatrin cannot do is we deliver both phasic and tonic inhibition. Why does that matter? It matters because we can cool down the entire environment around the neurons, whereas vigabatrin actually could never achieve that. Mechanistically, it theoretically could, but from a tolerability perspective, you can't. It can't get to doses where animals and humans can actually achieve tonic inhibition. So we think that we may have differential, not just tolerability from that factor, but also potentially efficacy. Got it. And then when do you think you could gather sort of the full seizure reduction effect from OV329? Would that give us from that open label? I'm wondering if that's like an eight-week endpoint or a 12-week endpoint, and would that allow investors to see seizure reduction activity, say, in 2026? Yeah. So for the phase II program for OV329, we're assuming eight-week studies. We think that's important if you look at historic guides to understand when seizure medicines like OV329 can show separation from placebo. You want to have at least five to six weeks. So we're well on the outside of that with an eight-week paradigm. Understood. And then, last question, going back to what Laura said about the seven-milligram. So it sounds like you are confident that that seven-milligram is getting you to the sort of ceiling effect of that pharmacodynamic range. I'm just wondering what other options may be in play, given that very, very clean safety profile that you have. It obviously changes the risk-benefit profile if that side effect profile remains that clean, the ability to dose up. Yeah. So we feel, first of all, Ritu, we feel very confident with the five-milligram dose that we have. So we're delivering inhibition that is competitive with vigabatrin and has what we think is a pretty superlative, potentially best in category safety profile with the five-milligram dose. So feel terrific about that. With that said, if we can push it further and not leave any seizure reduction efficacy on the table, that's something that we want to endeavor to do. And we feel that, as you rightly point out, the safety that we've seen to date is highly permissive to push that. So for the seven-milligram cohort, when you look at, again, drug exposure in the plasma that we are trying to achieve, that matches what we think is the really maximal area for pharmacodynamic seizure reduction, coupled with good tolerability, the seven-milligram dosoe delivers that. But we will be running it in a phase I cohort of just healthy volunteers. We're actively doing that now to qualify it for safety, tolerability, exposure, and PK. So we'll have that information in our hands as we begin to enroll the phase II- A program. And you mentioned something about titration, Ritu. We do not anticipate needing titration based on the profile that we have to date. Great. Thanks for taking all the questions. Thank you, Ritu, for the questions. The next question will come from Madison El-Saadi at B. Riley Securities. Hey, thanks for taking our question. Congrats on the data and a very nice presentation of the data set. Maybe on the 70-mg dose, would you expect this dose to ensure all the treated patients kind of reach that area under the curve threshold that's needed to achieve benefit based on your PK responder rate analysis? And then maybe on side effects, could you comment on the metallic taste? I believe there was one sedation. Is this something that kind of resolved after a couple of doses? Thanks. Yeah. Thanks for the questions, Madison. So in terms of addressing your first question, which was, what level of exposure would we expect to see at the seven-milligram dose? Would our PK help deliver that? So as we model our seven-milligram dose based on the data that we already have in human healthy volunteers and that regression analysis that you alluded to in our presentation, the answer is yes. Seven milligrams would put us squarely in a level where we would be expecting to see exposure in the brain well in the range of somewhere between 120 to 140 nanograms per hour per ml. We see that when we get to that level of drug exposure in the plasma, it is highly correlated to inhibition. And we would expect to see a very good responder rate. Even if you look at the modeling and the regression analysis from our five-milligram cohort, you see that we're currently delivering an exposure in the plasma of somewhere between 80 to 100 nanograms per hour per mL. We have a high degree of responders in that regression analysis that had very strong inhibition. Seven milligrams should just even further enhance that. To speak to your comments about the adverse events, metallic taste was something that we did see in one subject. There's not a clear explanation for why that was, but it was mild and transient and completely resolved. You're correct. In our two-milligram cohort, we did have one account of drowsiness. Drowsiness and sedation can be associated with inhibition in GABAergic drugs. What we are seeing with OV329 and what makes us very excited is we're not seeing significant tolerability issues. For example, with vigabatrin, you see actually a high degree of sedation at their therapeutic doses. We're not seeing that. Yet at the same time, we have now proven that we're delivering competitive and in excess inhibition to that mechanism. So this is what the field has always wanted to achieve. We want to have highly effective anticonvulsants that are gentler medicines. That's what the profile and what we believe the phasic and tonic inhibition of OV329 is allowing us to deliver. Understood. That's very helpful. Thank you. Thanks, Madison. Thank you, Madison. The next question comes from Miles Minter at William Blair. Thanks, everyone. Congrats on the data. I had two on the data and then just one on the seven-milligram dose. So the first one's on the cortical silent period data. You're showing a 10.4% increase in the FDI muscle, 6.7% in the APB. Just wondering how that compares to Dr. Rotenberg's expectations for that particular data that he announced at R&D Day. And then the second is on the LICI. I think in the placebo arm for the FDI muscle, that may have been numerically larger, the improvement there than we saw the 329. So is that just lower in numbers, noise in the data there? Just wanted that explained. And then finally, on the seven-milligram dose, is that pretty much just bringing forward the time to steady-state concentration as well? And are there any sort of drug-drug interactions that we should be aware of considering, I would imagine, these FOS patients are probably going to have three or more concomitant meds if you enroll them? Thanks very much. So I will try to get to all of those, Miles. So if I miss one, just flag it for me. So in terms of the performance on the cortical silent period, so Dr. Rotenberg works with us and advises us closely as an independent expert and one of the world leaders on applying TMS biomarkers to the evaluation of anti-seizure medicines. And basically, Alex would tell you, yes, this performance on the cortical silent period actually looks very good for a seizure medicine. And the reason why is if you look at our materials, what you'll notice is that therapeutic doses of vigabatrin have been studied in two different studies of healthy volunteers. In one study, a therapeutic dose of vigabatrin achieved a 19% increase. In another study, it showed actually no impact on the cortical silent period. So of course, we have moved the cortical silent period and prolongated it in statistically significant fashion. But what I believe Dr. Rotenberg would likely tell you of looking at the cortical silent period versus another biomarker like the long-interval intracortical inhibition is that the CSP, the cortical silent period, is probably a less specific predictor of this mechanism, so you can pick it up on TMS, but it might not be as specific as the LICI, for example, is, but nevertheless, we moved those parameters in a statistically significant fashion. I'll go next to your question about the seven-milligram dose, and I think you had asked the question. Hopefully, I addressed the comments about the exposure level that we believe it will deliver. In terms of steady-state and just overall performance of the seven-milligram in terms of the safety and we also know that we're hitting our target pharmacology inhibition by also three days. So what I mean by that, Miles, is that our strategy is to inhibit the GABA aminotransferase enzyme by roughly 50%-60% in that quarter. And we know that we achieve that after three days of repeated dosing. And because the enzyme turnover is very slow with very low but potent doses, we are able to keep the enzyme suppressed. So we know that we hit steady-state within that period of time. We believe, based on the safety and tolerability that we have in animals, and importantly, much more importantly, that we now have in humans, that we expect that the seven-milligram should perform very well. Miles, let me just take a beat there and see. I think you had an additional question about the seven milligrams, and let's make sure we cover that for you. It's just any sort of drug-drug interactions that we should be aware of. No. No. No. No. Thanks very much for the questions. Congrats. Thanks, Miles. Thank you, Miles. The next question comes from Jay Olson at Oppenheimer. Thank you for providing this comprehensive update and congrats on the impressive results for OV329. Looking ahead to your proof of concept study in focal onset seizures, could you please talk about lessons learned from previous focal onset seizure trials, especially with regards to managing placebo response? And how do the differentiating features of OV329 translate into potential clinical benefits versus other GABAergic anticonvulsants? And we have a follow-on question if we could, please. Very good. When we look at the landscape of focal onset seizures, we really benefit from being able to walk through the learnings that the field has had over time and that our peers are having, who we're also cheering for. This is a category where better medicines are needed. Most particularly, I think one of the things that we look a lot, of course, is at data capture. The field has improved very much when we think about electronic seizure diaries, how do we optimize our enrichment population relative to the number of ASMs they're on, the number of baseline seizures they're having to more optimally be able to catch change. These are things that we work hand in hand with the Epilepsy Research Consortium to do. We also have the benefit, of course, of being able to see the results that another GABA aminotransferase inhibitor, vigabatrin, had demonstrated over many studies over many years. But I think, Jay, when we look out at the next steps for 329, one of the things that we are most keenly focused on is, of course, enrollment. This is a busy area. We feel that we're very well positioned with a completely unique mechanism of action that seems to have really good safety and already has quantitative measures of inhibition far beyond what I think any other seizure medicine has had at this stage of development. But we're very much focused on enrollment, optimizing our sites to be able to ask the right questions and get answers. You asked an important question also, Jay, about so what does the profile of 329 look like relative to the treatment-resistant focal onset seizure landscape? We think it looks really good. The reason why is, there are not other medicines out there that naturally help increase your local or endogenous levels of GABA and tuning those in a way that is more optimal. When you think about other seizure medicines that are good anticonvulsants, they tend to surge GABA in the synapse primarily. That leads to some of the tolerability and side effect issues we see, such as sedation, dizziness, and headache. So by more optimally tuning GABA and bringing this differentiated mechanism to the fore that we don't anticipate titration, it will be once-daily dosing, highly potent, and it appears to also have on track to have very competitive seizure reduction based on what we see from the inhibition it delivers and what appears to be best in therapeutic area safety so far. So this could be a really meaningful medicine to people with epilepsies. Great. Thank you. That's super helpful. And I just want to follow up on the safety comments. It seems like today's findings support a level of ocular safety that could preclude the warning for loss of vision and the requirement for ocular monitoring that vigabatrin has. So we're curious if that clean ocular safety would eventually enable earlier lines of treatment with 329. Certainly, that would be something that we would like to pursue as part of our strategy, Jay. We felt, and thanks to our research team and my colleague, Dr. Zhong Zhong, we've spent an extensive amount of work de-risking OV329 in the preclinical well before we ever got into humans. With that said, we will continue to build an ocular and ophthalmic safety database, really starting today for OV329. And that will enable us, we believe, in our discussions with regulators to avoid the monitoring that vigabatrin as a class was previously subject to. So all of the safety and ophthalmic metrics that you saw in our phase I program, we will continue in perpetuity through OV329's development and also into open- label extension programs. This will allow us to build a very robust ophthalmic safety database that supports 329 and the registration package that we will take to regulators to avoid the monitoring that was needed previously with vigabatrin. Excellent. Congrats again. Thanks for taking all the questions. Thanks, Jay. Thank you for the questions, Jay. This concludes today's Q&A session. I'll now turn it back to Victoria for concluding remarks. Thank you, everyone, for joining today's event. As a reminder, a replay will be posted on our website following this call. Have a nice day, and you may now disconnect or.