Good morning, everyone. My name is Poorna Kannan, and I'm an associate here at Needham & Company. Thank you all for joining us today for Needham's 24th Annual Healthcare conference. I am very excited to present our next presenter, Meg Alexander. She is the President and COO of Ovid Therapeutics, and she will be providing us with a corporate presentation. Following that, we will open up the floor to any questions. Just as a reminder, you can send any questions that you may have, and I can weave that in. Meg, if you're ready, please take it away. Thank you. Good morning, Poorna. Thank you. I'm Meg Alexander. As Poorna said, I'm the President and Chief Operating Officer at Ovid Therapeutics, and it is my pleasure to tell you about our company today. Ovid Therapeutics is a neuroscience company, and we are dedicated to quelling conditions that are caused by neural hyperexcitability. We seek to relieve the symptoms that matter most to patients with brain disease and hopefully to one day halt brain disease. We are a public company, so I encourage you to regard our forward-looking statements. Our focus and our strategy at Ovid is to truly differentiate in the CNS landscape. We're pursuing fundamental biological targets that are really implicated either directly or indirectly in neural hyperexcitability. We are very much looking at targets that are differentiated that either go after neurotransmitters or ion channels. We're exclusively focused on precision small molecules that are highly specific to avoid off-target effects. We're going after differentiated mechanisms of action. Hopefully, in our future, we will see more medicines that help address brain diseases. What we are seeing in the space is many different development companies are pursuing the same targets. What that means is fast forward to the marketplace five to 10 years from now, and we'll see many competing programs trying to enroll in the same indications in terms of their clinical development strategy and also to compete with each other in the commercial marketplace. That's the situation we want to avoid. Beyond that, we want to create a real step change for patient care. We believe differentiated mechanisms of actions, again, going after exciting and fundamental biological targets in the brain, is the way to do that. We have the cash to be able to pursue our programs into the second half of 2026. This gives you a view of our pipeline. As I said, it's differentiated, and it has many exciting milestones coming up this year. I'll start at the top, and then we'll walk through this during the presentation. The program in green is our OV329 program. That's a GABA- aminotransferase inhibitor, and we're pursuing that for treatment-resistant epilepsies. GABA- aminotransferase is a validated mechanism of action, but historically, the class has had safety issues. We believe we have dialed that out, and we are completing a phase I that will move into a phase II program early next year. We're expecting a pretty significant card turnover in the third quarter of this year. Specifically, we have a phase I readout, which has all the traditional things that you would think of from a phase I trial, safety, tolerability, PK. We also have five different biomarkers that we're measuring in the study that give us a good sense as to the clinical effect that we may see in our phase II program. That is coming up just a few months from now. Also very exciting is we have a complete portfolio of KCC2 direct activators. KCC2 stands for potassium chloride cotransporter 2. This particular biological target, KCC2, has been the great white whale of neurology. This is specifically the target that many companies have sought to drug because it is a master switch, so to speak, on neural hyperexcitability. Historically, it has been a very challenging target from a medicinal chemistry perspective to drug. We have done it, and we have multiple unique programs coming out of this portfolio. The first program, as you see in the couple rows down, is OV350. That is an intravenous formulation. We are actively dosing that in humans right now. We were the first company to ever dose a direct activator of KCC2. We are expecting results from that phase I trial at the end of the year. This time next year, we will be putting our first oral KCC2 direct activator into the clinic. That behaves very similarly to the IV. For both of these indications, we are looking at psychosis associated with Parkinson's disease and Lewy body dementia. Behind that, we have another oral that has unique attributes as well. A very prolific pipeline, and we expect, particularly from the KCC2 portfolio, that we'll be having an IND every year for the course of the next several years. It gives us a lot of optionality. First, I'll take us into OV329. As I mentioned, this is designed to be a next-generation and best-in-class GABA- aminotransferase inhibitor. This is a validated mechanism, and we sought to pursue OV329 to supplant a known medicine, which was the brand name was called Sabril, and the generic name was called vigabatrin, which was a very powerful anticonvulsant that came to the market now almost 30 years ago. Despite being a powerful anticonvulsant, it had one very significant Achilles heel in which they discovered that after it was marketed, certain subjects who were taking vigabatrin ended up having retinal degradation that led to irreversible vision loss. Very significant problem. As a result, that medicine's use was significantly curbed. We have sought to dial that out, and we believe that we have. As I mentioned, we're in the clinic now with a readout expected in Q3 of this year. Really, the premise of OV329 is to deliver the optimal amount of GABA. I'll take you through the mechanism of action in a moment. What we see today is that there's still so much need in epilepsy. You may hear a lot about epilepsy medicines, but there's more than 50 million people across the world, about two and a half million people here in the United States that live with epilepsy. What's so significant is there's no cure today, just absolutely none. About 1/3 of patients remain treatment-resistant despite a panoply of medicines that exist. For these patients, they don't need more of the same mechanism of action. They need new. They need something different that will help create a step change. If you're still resistant to medicines, adding more of the same is not necessarily a good strategy as a clinician and as a patient. That's what we seek to bring to bear. This is really important because so many of the patients who are resistant are actually on multiple medicines, five or more. In fact, about half of them are. What we're looking to do with OV329 is find a medicine that delivers the optimal amount of inhibition by increasing GABA, but not so much that you get some of the tolerability side effects that happen when these patients who are resistant are taking polypharmacy regimens. We believe with OV329, we've solved for much of this. As we've seen before in other medicines that act on GABA, the inhibitory neurotransmitter in the brain, oftentimes they're short-acting. As I mentioned, they put patients to sleep. The prior medicines, you heard about the vision effects, but they also have very high dosing. They really bombard the CNS to try to suppress it. With OV329, we have a very differentiated target product profile. We have durable inhibition. I mentioned before we want to create just that right balance of GABA. We do that because we have something called phasic and tonic inhibition. What that means essentially is that we're increasing GABA in the synapse, but also in the extrasynaptic region. What that means is we're creating an overall inhibitory neural milieu to keep the brain and neurons not hyperexcited, but also not overly sedated as well. Importantly, we've seen no signs of the ocular changes that occurred with the first-generation medicine vigabatrin. We can show you some of the data supporting that. We're very excited at this point because we're moving very close to patient trials. As I mentioned, we'll be finishing the phase I in the third quarter, and we expect to move into epilepsy programs at that point, starting a phase II program in Q1 of 2026. We'll be looking at developmental epileptic encephalopathies as well as adult treatment-resistant epilepsies. This gives you a broad overview of how we differentiate from vigabatrin. You'll see OV329 is on the left and vigabatrin is on the right. It's a different compound entirely. We actually got this compound out of Northwestern, where it was invented by a gentleman called Dr. Rick Silverman. He's actually the same inventor of Lyrica, another known and important medicine. Really, the key difference that Rick designed with OV329 relative to the first-generation medicine vigabatrin is we are highly more potent. In some cases, greater than 100, even to a thousandfold more potent than the first-generation medicine. We bind irreversibly. Importantly, we deliver that phasic and tonic inhibition. That allows us to be able to get to that right balance of GABA in the brain. Unlike the first-generation medicine vigabatrin, we have a therapeutic index where you don't see any signs of adverse events or toxicities. This is very different from vigabatrin, where even a sub-therapeutic dose of vigabatrin, you start to see ocular changes in the eye. The way essentially OV329 works, putting it very simply, is that it increases endogenous levels of GABA. It does so by inhibiting the GABA- aminotransferase. GABA- aminotransferase essentially is the enzyme that eats GABA, the inhibitory neurotransmitter. If you reduce GABA- AT, you're able to increase levels of the neurotransmitter in the brain. It does so very efficiently, as I mentioned, given our potency. I'm pleased to share we are in and completing a phase I trial right now. As I mentioned, we have a number of biomarkers that are very helpful because prior anti-seizure medicines have been studied with these biomarkers. Importantly, they give us a good read-through for clinical effect and target engagement. We'll be looking at a number of parameters using transcranial magnetic stimulation. For any of you who are familiar with epilepsy drugs, this is a tool that's been used before to be able to show signs of GABAergic activity in the brain. We also will be using magnetic resonance spectroscopy. That allows us to see increases potentially of GABA in certain levels of the brain, certain regions of the brain, rather. We'll also be studying safety, PK, tolerability. As you would appreciate, trying to replace a medicine that had a safety issue, and specifically an ocular safety issue, we're conducting very extensive visual monitoring of these subjects and will do throughout the entirety of our clinical development program. We've seen no adverse events associated with OV329 to date. Any AEs that we've seen have been mild, very transient, and low grade. We expect to read this out with the biomarker and the safety data in just a couple of months in Q3. As I mentioned, you know at this point, we know with OV329 that we penetrate the brain, that we have anticonvulsant activity across a range of animal models that were highly potent compared to vigabatrin. Very importantly, and this we believe allows us to differentiate in part because of from vigabatrin, is that we clear the tissue very, very quickly. What happens with OV329 is it gets into the brain, it inhibits the GABA aminotransferase enzyme with very precise small doses, knocks it down. Because the durability of OV329, it's an irreversible inhibitor, is so prolonged, we can come back with another very small dose and keep that enzyme suppressed. We clear the tissue very rapidly. We have a very quick tissue clearance profile. This is enabling us to get in, deliver the anticonvulsant activity, but get out and not see any of the safety issues that we've seen with the prior generations of this class. What you're seeing here is a sign of just all the anticonvulsant models that we have run OV329 in. You can see nine different chronic and acute models here all show anticonvulsant activity with OV329. Just to put this into context, Keppra, which was obviously a very successful medicine, worked in one. This gives us a lot of encouragement and helped propel us into human clinical trials. Of course, the big question with this medicine is safety. Because if it's a validated mechanism of action and efficacy, a big piece of what we have been endeavoring to prove is the safety profile. Beyond the efficacy that we've seen in the animal models, we have run a battery of different safety tests, particularly focused on the ocular changes to be able to prove that they do not manifest with OV329. What you're seeing here is one of the crucial studies. This is a very sensitive animal model. It's conducted in actually Sprague- Dawley albino rats because they're one of the most sensitive species to ocular changes. The image really says it all here. What you see on the left is OV329 at a therapeutic dose in animals. On the right, you see vigabatrin at an equally therapeutic dose. They're dose-adjusted and they're on par. Essentially what you're seeing is a slice of the back of an eye of the rat. What you're looking for is these little purple bands in the middle. As you can see on the right, vigabatrin, after just 45 days, we start to see the retinal cell dysregulation there, which we believe is the cause of the ocular toxicity. If you look on the left, the same therapeutic dose, same amount of time, you see nice tight banding of the retinal cells with OV329, which is what you should do. That was very encouraging. To truly show their safety profile, we essentially ran the killer experiment, which is what you're looking at here. There have been independent studies that show vigabatrin preferentially accumulates in the retina. We sought to essentially replicate those models and run it head-to-head, vigabatrin versus OV329. What you're seeing here is the results of that work. We basically controlled for exposure and plasma level, and we were able to show that OV329 gets into the brain, the plasma, and the tissue. We sacrificed some animals right away so we could see that. It clears it very, very rapidly. OV329, like I said before, gets in, does its job, and gets out. Vigabatrin, in less than 48 hours, we saw four-fold preferential accumulation in the retina. There is something truly idiosyncratic about the vigabatrin compound. As I mentioned, we have the readouts coming up in just a couple of months with our human trial. There are some very specific parameters that we are looking at for our biomarkers. We are looking at ones in which we know the first-generation medicine was able to move the needle. On TMS, that includes some of the metrics you see on the left, the long interval intracortical inhibition and the cortical silent period, as well as increasing GABA in regions of the brain. We feel that if we're able to directionally move these same parameters and potentially do so with the same magnitude, that should give us a good sense of how we'll perform in the clinic because we have data that shows what a therapeutic dose of vigabatrin had done in these parameters. This just gives you more of a sense of what those parameters look like. Importantly, we're looking for signs of GABAergic activity, which is what a number of these metrics measure. We also have some negative controls in place because we want to make sure that OV329 isn't operating in a way that it shouldn't. We have one of the world-leading experts at Harvard advising us on this protocol. What we believe we'll be able to do coming out of our phase I trial is we'll immediately be moving into a II-A program where we will be taking two doses into adults with treatment-resistant epilepsies. Specifically, we'll be measuring focal seizures in these subjects. What this will allow us to do is confirm effect size as well as our therapeutic dose that we want to take into pivotal trials. This will be really important because it allows us to have a read-through to multiple indications. By studying adults with focal seizures, we can potentially go into the adult treatment-resistant epilepsy market, which, as you can see here, is quite large, even if you assume only a 10% market share penetration because it's a very competitive landscape that's still more than a billion-dollar opportunity. However, we also have the opportunity to go into developmental epileptic encephalopathies, as I said earlier, also a very significant opportunity with tremendous unmet need. This gives us an opportunity to serve those DEEs, for short, that have focal seizures. This is also an area where patients are willing to trade off risk-benefit profile. In a situation where we have a very clean profile, but we have slightly more tolerability considerations, DEEs would be a very natural place to go. We have lots of optionality in that program and some really significant progress coming up this year. Now I'd like to turn to our KCC2 direct activator portfolio. As I mentioned, this has been the great white whale of neurology. Many, many companies and clinicians have wanted to drug KCC2, but it's very hard to directly activate a cotransporter. Why this is so exciting is it really is a master switch on neural hyperexcitability. What it enables you to do by directly activating KCC2 is restore the inhibitory strength of endogenous GABA in the brain. It lets your inhibitory neurotransmitter do its job more effectively. We are the only company that is known that has direct activators of KCC2. We were the first company earlier this year to be able to drug humans with KCC2 direct activators. As I mentioned, this is not one program. This is a portfolio. We have more than 100 unique compounds in this library, the first three of which are moving rapidly into the clinic. Why KCC2 is exciting beyond the fact that it's this master switch for excitation is it's a very precise mechanism of action. KCC2 is only expressed in the brain and the spinal cord. Others have looked at other potassium chloride activators before or cotransporters before, but they're expressed in other organs in the body, which can lead to off-target effects. By going after KCC2, we can have a very precise impact. KCC2 sits downstream from many genetic and acquired causes of neurological dysfunction, which is why it's oftentimes considered the final common pathway. What's important is, unlike other targets in the brain where you can over or underdo it, as I said earlier, it's very hard to over-modulate KCC2. Energetically, it's difficult for the cotransporter to express too much chloride from the cell. It's just this very precise hitting that optimal balance, which is so important for the patient tolerability and safety. Bear with me. The slides skipped a little bit. You're hearing me speak to this is how it works. Essentially, KCC2 enables GABA to work better by managing and maintaining the right homeostasis within the neuron itself. It does so by balancing potassium and chloride. Essentially, by extruding the right amount of chloride, it allows GABA to be able to work again, and it helps mitigate that neural hyperexcitability. These are our first three programs coming out of our direct activator portfolio. OV350 is in the clinic right now. We know from the work that we've done across this whole portfolio that it has a range of different properties, including antipsychotic properties, as well as potentially anticonvulsant and anxiolytic properties. When we had initially in-licensed the entire direct activator portfolio, which we did for AstraZeneca at the beginning of the COVID pandemic, we had liked this whole portfolio a lot because we thought they would be very effective anticonvulsants. They will be, and they are. Our Chief Scientific Officer took a step back and did broader phenotypic screens of the entire library. What he discovered is that many of our compounds also have a very profound effect in psychosis. As we looked to put these compounds through phenotypic screens and then disease model screens, because we have so many compounds in the library, what we've been able to do is very strategically sequence the right compound for the right indication. For the first two programs, OV350 and OV4071, which is our oral KCC2 direct activator, they showed very profound effect in psychosis models. That is why we'll be pursuing psychosis and Parkinson's disease and Lewy body dementias. OV350 is in humans right now. We have a very permissive safety package. We expect to be completing this trial in the end of Q4 of 2025. What's also exciting, based on that target product profile that I mentioned before in the sense that we can't over-modulate KCC2, we can't over-activate it, we're not seeing any signs of sedation. We have got a very good first molecule going into the clinic, and we have got an exciting oral coming right behind it. This is some of the data that gave us early conviction. As I mentioned, we liked KCC2 for epilepsy and still do, but the data that you are seeing on the left and the right here was what helped point us in the direction of psychosis. All the colorful images and the purples that you are seeing on the left here are the outputs of a model called the Smart Cube. The Smart Cube essentially is a phenotypic screen, and it is a reference model that compares OV350 and our other molecules to other reference products. Essentially, the purple colors that you are seeing here are signs of similarities to typical and atypical antipsychotics. The yellow is actually a sign of anxiolytic properties, so anti-anxiety properties. What was exciting with OV350 is we saw the onset of effect within 15 minutes, and we saw dose response disappearing within 16 hours. Very amenable to chronic dosing. On the right is conformatory data that we actually ran. This is a model where you somewhat make the animal crazy. This is a phencyclidine-induced psychosis. You can see where you start the drug. What you're seeing here is essentially a dose-dependent response. Every line except for the green and the gray is OV350. You're seeing a dose-dependent response in the psychosis model that actually is comparable with clozapine. This was very exciting to us, and it is what helped point us in the direction of going into psychosis. What was exciting in the data that we saw was the oral program, OV4071, phenotypically behaves very similarly to OV350. We have a number of learnings that we're going to get out of our phase I program for OV350, the IV, that we'll be able to translate into the oral program. OV4071 is that oral program. It has a potency that's 20x greater than our IV program, OV350. It behaves very similarly in the disease and phenotypic screens, as I just mentioned. It's got very good safety margins, excellent tolerability, consistent plasma exposure, and we're in IND-enabling studies right now. This will be, we believe, a very big opportunity in psychosis associated with Parkinson's disease and Lewy body dementia. This was some of the data for OV4071 that gave us conviction. This is similar to that phencyclidine model that I just showed, except this is the oral program that you're seeing here. Again, on the right, you're seeing a dose-dependent response in a psychosis model to OV4071. We believe this is a huge opportunity because psychosis in Parkinson's disease and Lewy body dementia is, one, very prevalent and, two, extremely underserved. We know that roughly 30%-40% of people with Parkinson's disease will experience psychosis as their disease progresses. In Lewy body dementia, it's actually much more prevalent. It's about three out of four patients will end up having psychoses. We know that the hallucinations that oftentimes manifest with these types of psychoses are actually driven by neuronal excitation and hyperexcitation. The challenge for these patients is they can't take the kind of traditional atypical antipsychotics because it's contraindicated for the other medicines they have to take for their movement disorder. There's only one medicine out there that's branded, and it only works in about 12% of people that have psychoses associated with PD. Lewy body dementia psychosis has absolutely nothing. These are not only patient communities that need new medicines and better medicines, but it's also a great area for us to walk down for the KCC2 portfolio because we have a clinical path that we can understand from the other medicines that have developed here, including the one that only 12% of the population responds to. There are known endpoints. We can get a more homogeneous population because there's ways to essentially skin biopsy these patients for synuclein, which is a confirmatory sign of their disease. There is a known regulatory pathway, and there's a significant unmet need and market opportunity. This is a protected and branded space within areas of psychiatry. As I mentioned, this is a very big opportunity for those who are able to develop effective medicines. You can see on the right here, just giving you a projection of what the opportunity is, there are more than 1.4 million people in the United States who have psychoses associated with Lewy body dementia and Parkinson's disease. Assuming we just penetrate 5% of that market, it is a very significant opportunity, more than $2.5 billion. This is a big year for Ovid. We will be reading out our OV329 program in the third quarter, and we will be moving quickly into a phase II program with adults for treatment-resistant epilepsies. We have multiple events coming out of our KCC2 portfolio. Also within the next year, we expect data from our OV350 program at the end of the year, and we expect to be putting the first oral direct activator of KCC2 into humans this time next year. We have the capital to pursue our pipeline into the second half of 2026. With that, Poorna, I will take a pause and happy to address any questions. Thank you so much, Meg, for that wonderful presentation. Yeah, we have a few questions here, so I'll just go the order. One question is, could you elaborate on how OV329 is differentiated in this market, like compared to some of the other therapies in development for epilepsy and DEE? Some of the names that were brought up Vormatrigine by Praxis, and there's also the Bexicaserin by now Lundbeck. Yeah. Yeah, happy to address it. It's a wonderful thing for patients that there are more medicines and mechanisms of action coming to bear and coming through clinical development. What I'll say from a differentiation perspective is OV329 is one of the only medicines out there that will endogenously increase GABA. When you actually start to look at across the epilepsy landscape, what you'll see is there are good medicines hopefully coming to patients, but you see a very competitively dense landscape in certain target areas. For example, Bexicaserin, I think, will be one of four or five potentially HT2 mechanisms, right? You have to think about, if you're competing in that space, two factors. One is you have to have superior safety tolerability and pharmacology because you'll be competing against mechanisms of action that are very similar to yours or the same as yours. That's point one. Point two is for patients who are treatment resistant, which you've now heard is many of the epilepsy community, having more mechanisms that are all activating the same target in the same way doesn't help clinicians, right? They need differentiated mechanisms of action. OV329 is different in the sense that it endogenously increases GABA. It irreversibly inhibits the GABA- aminotransferase. It's highly potent, but it doesn't have the level of sedation and over-modulation that you see with certain medicines. Other GABA-acting drugs tend to flood into the GABA into the synapse. What happens? It makes people very sedate, right? Sedated. You can have other drug-drug interactions. We don't see any of that with OV329. We expect to have a very clean profile. We haven't seen any signs of sedation, and we're trying to get that optimal level of inhibition in the brain without overdoing it. Okay, that makes a lot of sense. The other question we have is, in terms of the phase I data that's expected in third quarter, I guess, what is the benchmark for the clinical effect? Also, how many patients will we be seeing the data from? For the other cohort that you've added, is there a higher dose because you have a clean safety profile? I think the last one under that is you mentioned that you need to show the safety, right? Like from a regulatory perspective, how many patients do you need to show the safety in phase I so that you feel comfortable to go into phase II? Excellent questions. Let me see if we can get all of them. I think you had four or five there. Sorry. If I miss one, keep me honest, Poorna. Our phase I trial, let's start with that, and we'll go ahead and begin with how many subjects we'll see and what to expect, and then we can go into some of the other questions. In terms of the phase I program, we will have about 45 participants in total from that phase I program. That That will include some placebo subjects. In terms of what you should expect to see from the results, we had some placebo subjects in the cohort very intentionally. As I mentioned, there's five different biomarkers that we're studying. What we're looking for is directional movement in the same areas that either vigabatrin, the first-generation medicine, worked in, or other GABA-acting medicines have worked in. The beauty about epilepsy is many of these anti-seizure medicines have been studied using things like TMS and MRS before. That can give us some sense of comparability, not for every one of the metrics that we're looking at, but for many of them. What we'll be looking for coming out of that program is signs of clinical effect, so pharmacodynamic effect from the TMS study. There are certain parameters that we know that if there's a slowed reaction time, that's signs of GABAergic activity in the brain. We've seen that, and it's been demonstrated with vigabatrin before. We can have that comparability that we can hold up. With magnetic resonance spectroscopy, or MRS, which is a lot easier to roll off the tongue, we will be looking for increases of GABA in the brain. This will be the participants' untreated baseline compared to their treatment seven days later. Finally, we also will be looking at EEG, and there's certain frequency bands that we know are associated with GABAergic activity. We will have those as well. Directional movement on some or many of these would give us a sign that we're hitting the target, so we're inhibiting GABA- aminotransferase, and that we're having a pharmacodynamic effect. That would be very exciting. It's a lot to get out of a phase I program. The next questions I think you would ask, Poorna, was about the ocular safety. How do we prove that? How many patients does safety need to be exhibited in to feel confident? Right now, we have five different metrics that we're using to monitor subjects in our phase I program. Those five metrics will be what we carry through for the entirety of the clinical development of OV329. That is because when we get to registration period, we do not want to have the same monitoring and label that vigabatrin was subject to because it was that REMS program that significantly curtailed its use. Obviously so because it made certain subjects irreversibly blind. That is very important, and we will do that because we want to have a clean label at the end of it. In terms of how many subjects you need to show safety for, I think that is probably the wrong way to look at the question. What I would say is the duration of time that you have people treated with OV329. Vigabatrin, that was determined, its ocular issues were determined post-market. If you go to subject matter experts who treat with vigabatrin and who have their own registry, so to speak, within their healthcare systems like UCLA and the Cleveland Clinic, most of the expert epileptologists will tell you that when the toxicity is seen in patients, it is usually somewhere between two to six months. Using that in mind, it is our intention to not only have the clinical development program, but to have patients on OLEs, open-label extension programs for long periods of time because we want to be able to showcase that we have cleared that benchmark and that we are not seeing the ocular changes show up. We do not expect to. All the science is pointing to the fact that this is idiosyncratic to vigabatrin as a compound and not the class. There is lots of other data that show that inhibiting GABA- aminotransferase indirectly or increasing levels of GABA in the brain and eye do not cause ocular changes. We do really think it is unique to vigabatrin based on all the data that we have in our hands. Nevertheless, we will do this to prove the safety of OV329. I think the one more question was around regulatory. In terms of regulatory, is there a patient pool that you need to show, demonstrate the safety, or is it similar? It is more about the duration even from that perspective. Certainly with all medicines and clinical development, we will have to have obviously a significantly sized safety database and patient year exposure, patient exposure. That you would expect with any drug development. Really, it is the time on medicine, which is what most clinicians want to see. Because you have to keep in mind when vigabatrin was first launched, the field was very excited about it as a mechanism of action. It is to endogenously increase GABA is ideal versus trying to surge something in the system. Clinicians really liked it, but then they felt very burned when the safety issue was discovered post-market. For us, it's extremely important that we have long-term exposure for all the subjects in our programs because we think that's going to be what clinicians are going to need to see to feel comfortable. Okay, that makes a lot of sense. Another question we have is, what is the therapeutic index of this drug? Do you anticipate taking multiple doses into phase II to study? We do. We do. What's really unique about OV329's profile is we have an unusual PK/PD because we irreversibly bind to the enzyme. We're able to get in, knock down the enzyme, and clear the tissue, but we have an enduring pharmacodynamic effect. What that enables us to do then is have a pretty broad dosing paradigm and therapeutic index that we can work within. As I mentioned, we're in human trials right now. We have good safety margins for that, 5x for the dose that we just completed. We have a lot of confidence within the paradigm that we have, that therapeutic index. We also have flexibility within it too that we could potentially dose higher, particularly for patients where the risk benefit is very, very, very amenable to them. In terms of obviously, it's a little bit different than healthy volunteers in that sense. We're feeling very good about that. You asked the question of, did we add a higher dose cohort? We did. We felt so encouraged by the clean profile that we were seeing in our last cohort of OV329 that we decided to add one more terminal cohort. We actually doubled the size of that cohort because we have such strong biomarker opportunities. We want to try to not leave any questions on the table. We're very hopeful that we'll be able to move a number of those biomarkers, and we want to be able to have a robust enough cohort to be able to show that. That makes a lot of sense. Similarly, for OV350, the data that's expected end of the sale, what can we expect from that data? Is there any kind of clinical benchmark? Yes. This will be really important to the entire portfolio of KCC2 direct activators. Because this is a first-in-class medicine, safety and tolerability is huge here for us, right, as well as PK. Importantly, we also will be looking at a biomarker, which is exploratory. It is quantitative EEG. That will be helpful to us as we start to look into the oral program that we will be initiating this time next year. We will learn a lot about that. It will help us as we develop the series of medicines that come behind that. Again, first time we are ever going into humans with direct activators. Establishing that safety and tolerability is very, very important. We believe OV350 will give us a lot in terms of that. Is there anything that you are looking for specifically in this quantitative EEG that makes you confident to go for the next generation? Yeah, yeah, yeah. Thank you for asking the question. What we're looking for is basically signs of target engagement. What we don't know is in a phase I trial, and this is why it's exploratory, we don't know whether or not the chloride gradient is disrupted enough in a healthy person versus someone who's in a disease state to be able to be picked up with quantitative EEG. We think there's a possibility, which is why we're measuring it. That way, if we're able to show that we're changing the chloride gradient, we'll be able to show that we're having that target engagement effect in the brain as we seek to have. We think there's a reasonably good opportunity for this. We've got a very broad dosing corridor with OV350, which is super to be able to characterize the safety of the class. That's what we hope to see. Again, it's exploratory. It might be a more meaningful biomarker in a patient cohort that we'll be running next year. That's what's really important. We expect to get to proof of concept pretty quickly with the oral KCC2 direct activator because we're going to hang a I-B off of our phase I next year that will actually have patient cohorts in it. This is all setting up basically the programs that we seek to unfold for the orals in 2026. Okay, great. Awesome. Thanks for that additional color. With that, we're at time, and this is kind of all the questions that we have for today. To our listeners, thank you for joining us, and hope you have a good rest of your day. Thank you. Thank you, Poorna.