Good afternoon, everyone. My name is Athena Chin. I am an Associate here at TD Cowen. Thank you all for joining us this afternoon. We have Meg Alexander, President and COO of Ovid Therapeutics, providing a corporate presentation. Following that, we'll open up the floor for any questions. Meg, please take it away. Thank you, Athena. Good afternoon, everyone. I'm Meg Alexander. I'm the President and COO of Ovid. At Ovid Therapeutics, we're a company that is dedicated to quelling neural hyperexcitability, which is relevant across a number of diseases, including seizures, epilepsies, and different forms of psychoses. We are a publicly traded company, so I encourage you to take note of our forward-looking statements. I've been excited to talk to you about Ovid today because we're a very differentiated company. It is our desire to be a leader in neurotherapeutics, and our strategy is that we are very much focused on going after foundational biological targets in the brain. We primarily have medicines that are targeting neurotransmitters or ion channels, and we're focused exclusively on highly specific small molecules. They're small molecules, but they may unlock very significant therapeutic opportunities. Our cash balance at the end of Q3 2024 was $62.7 million. As I mentioned before, we have a pipeline that seeks to be differentiated. As you look across the field of neurology and you look in development pipelines for epilepsies and even other forms of psychiatric medicines, what you'll see is there's many mechanisms that are going after the same target. In certain areas, there's a high degree of a sea of sameness. We have sought to be very different from that, so we have curated our pipeline very intentionally to go after first-in-class or best-in-class mechanisms of action. Looking at the top of our pipeline and walking down, our lead clinical program is OV329. That's the bar in green. This is a GABA-aminotransferase inhibitor. Inhibiting GABA-aminotransferase is a validated target and a validated mechanism of action. This program is currently in phase I, and we're expecting a readout later this year. It's not a traditional phase I trial. We are looking at safety, tolerability, and PK, as you would expect, but we're also looking at some really exciting biomarkers that should give us a sign of target engagement and a pharmacodynamic response, potentially. OV888 is our ROCK2 inhibitor program. This is a really exciting mechanism of action for neurovascular conditions. This program has been cleared by regulators to proceed in phase II trials, though we decided to pause it temporarily as we look for regulatory feedback from a competing program in the lead indication that we wanted to go after, which is cerebral cavernous malformations. It's a very big opportunity, and it's an interesting area, but it's also a relatively new area of clinical study, and we want to see how the FDA responds to a competitor program that's a very different mechanism of action than ours. Finally, at the bottom of our pipeline, this is not just one program. This is a platform of medicines, and that is the KCC2 platform. KCC2 stands for potassium chloride cotransporter 2. You know why we say KCC2. KCC2 is a fundamental target in the brain that has broad therapeutic potential, and we have a lot of potential within the platform itself. This is not one program. It's multiple programs that have unique structures, unique formulation amenability, and that behave differently. There is some red thread, but some unique nuances with different programs within this platform itself that gives us a tremendous amount of strategic optionality. KCC2 is one of the targets that medicine has long wanted to drug, and it is a particular challenge to drug a cotransporter. We now have done it with the lead program, which is going into humans in Q1 of 2025. That is this year and very soon. We have a number of programs behind it too that give us a lot of strategic optionality. We are very excited by this program, and there are a number of milestones that are coming up over the course of the next 12 months-18 months. The first one, as you heard me say before, is for our OV329 program. This is in drug-resistant epilepsies, and we'll have the biomarker data that I mentioned that are signs of pharmacodynamic clinical effect, target engagement later this year, in addition to the safety. As I mentioned, our KCC2 program, the lead is OV350. That's in an intravenous formulation. It'll give us really nice information on safety and tolerability, PK, as well as an exploratory biomarker that's going into humans this quarter. We expect it to read out early next year, and we're very thrilled to have an oral program behind this, which will be going into humans this time next year. It should allow us to dose both acute and chronic indications. I'm going to start with our OV329 program. The story with OV329 is, you've heard me say the mechanism is a next-generation GABA- aminotransferase inhibitor. What we endeavored to do with this program was to go out and build a better mousetrap. We know that GABA-aminotransferase inhibition works because there was a first-generation medicine called the brand name was Sabril. The generic name was vigabatrin. It was very effective at reducing seizures. The challenge is, in the post-market, it was discovered that it also irreversibly caused retinal degradation in a subset of patients and made them blind. Tunnel vision, literal tunnel vision. Big problem. What we endeavored to do was we saw the mechanism of action and saw the therapeutic potential. We also saw the sales. Our CEO and our founder sat on the board of Lundbeck at the time, and he could actually see the global sales of Sabril and vigabatrin. It was nearly $1 billion-dollar drug, despite the fact that it made people have this irreversible blindness, a subset of the patients who took it. We said, can we build a better mousetrap? There was a medicinal chemist at Northwestern named Rick Silverman, who happened to be the same person who invented Lyrica. He had made it his career's next major chapter to try to come up with a more effective and safer GABA-aminotransferase inhibitor. We think he did. We in-licensed it from Northwestern, and that program is OV329. We intended it to be a best-in-class next-generation GABA-aminotransferase inhibitor. We know it's a validated target as an anticonvulsant and in reducing neural hyperexcitation. It's 100x more potent than vigabatrin, but it behaves very differently in some ways. We know that it's got irreversible binding. It's highly potent, but it clears the tissue very rapidly. What we've been able to characterize in animal models, and based on the human safety data that we've already seen, is that we clear the tissue very rapidly, but we have a prolonged pharmacodynamic effect with OV329. Very precise doses deliver prolonged and powerful inhibition, and they do so in such a way while still clearing the tissue and not accumulating in the back of the eye, which we've been able to show that vigabatrin does, and other independent experts have been able to do that too. Collectively, we think this profile is potentially going to enable treatment of potentially several different forms of epilepsies, and the idea of essentially quelling neuronal hyperexcitability by increasing endogenous levels of GABA could take it in a number of different directions. Epilepsy is the area that we're most excited about early on. The mechanism of action is quite simple. Essentially, GABA-aminotransferase is the enzyme that catabolizes GABA. It's the enzyme that eats GABA. If you inhibit GABA-aminotransferase, you get more ambient levels of GABA, the inhibitory neurotransmitter in the brain. What we think is quite interesting about OV329 is that it induces not just phasic inhibition at the synapse, but it also induces extra-synaptic inhibition, the atonic inhibition. What we're doing is we're essentially getting it to a state in the brain where we have this basically more optimized level of ambient GABA, and it's helping keep a hyperexcited neural system appropriately suppressed. That's really important because the challenge with all these anti-seizure medicines today is it's easy to overdo it. You might be able to crush the seizures, but then you start to increase the sedation very heavily. That's a problem for any patient that's on multiple seizure medicines, which many of them are. Being able to effectively optimize the level of GABA, tune GABA more eloquently—so that, or elegantly is the word I was looking for—so that we don't overdo it with the sedation is really key. I think I mentioned before when Sabril and vigabatrin came out, there was huge excitement in the field because it was a very effective anticonvulsant. When the safety issue with the vision was seen post-marketing, it significantly minimized where vigabatrin ended up being used. Nevertheless, it still actually had reasonable sales globally, nearly $1 billion, despite having a black box warning and having REMS required. We think the opportunity, if we're able to develop 329, to have the efficacy that we believe it will hold, coupled with preferable safety and without the sedation, could be very, very promising. Certainly, based on the best work that we can do with animal models, it indicates that it should be a powerful anticonvulsant. In the field of epilepsy, we're very fortunate because anti-seizure models in some of these animals are more translatable than others. We've put, at this point, OV329 through a large battery of anti-seizure models. What you can see is that it's effective in nine different models of chronic and acute seizures. We're not seeing any sedation in the animals. Just to give you some context, Keppra, which was obviously a very successful and important medicine, was effective in one. We feel quite encouraged by this. The real question for those who are interested in our 329 program is, can we differentiate on the safety? We have done a tremendous amount of characterization work here, both doing the models that the regulators require, but also just asking the tough questions that we in the community want to have to give us the confidence to move forward with human clinical and patient development. You have heard me talk about the potency. We know we penetrate the brain, but it is really the rapid tissue clearance coupled with this irreversible binding that we think is differentiating 329 from vigabatrin. We clear the tissue very, very rapidly. What's happening, just like with a very precise and low dose of OV329, we get into the brain, we knock down the GABA-aminotransferase enzyme, and then when we come back with, again, a very small and potent dose, we're able to keep that enzyme suppressed and we clear the tissue. This is unlike what we've seen with vigabatrin. The visuals that I'm holding up behind me, the green is OV329, the red is vigabatrin. Essentially, we did what we considered to be a killer experiment to really ask the question of, do we accumulate in the back of the eye, as vigabatrin has been shown by independent researchers to do? What we found from this is that within less than 48 hours, a sub-therapeutic dose of vigabatrin, so a dose that's not even an anticonvulsant level, started to accumulate in the back of the eye, four-fold, actually greater than what we see in the plasma, and OV329 did not. We were able to confirm that we get into the brain and get into the plasma, but it was undetectable. There is something going on that does preferentially accumulate with vigabatrin in the back of the eye. In the exact same model, we're not seeing it with OV329. We think there's a huge potential opportunity here for a safer GABA-aminotransferase inhibitor. The natural areas that we'd be looking to walk down is treatment-resistant epilepsies, of which there are huge populations, both in adults, but also in pediatrics and in pediatric developmental epileptic encephalopathies. There is a need for new mechanisms of action out there. If you have failed the existing mechanisms of action, then taking an MOA that endogenously increases GABA could be very relevant for you. We are very excited about this. It is why we are investing the time to do our phase I right to give us multiple dosing opportunities to potentially take into multiple phase II opportunities in the future. Where we are in the clinic with humans, many of you know, some of you in the room are shareholders, know that we are in a phase I study right now with OV329. We have said publicly that the human safety has been extremely amenable. There have been no serious adverse events, and the adverse events have been extremely mild and transient, like headache. We decided, based on the superb human safety that we were seeing, that we were going to add another cohort to the phase I study. We're expecting to read that out later this year. We have a filing coming up soon. We'll put more detailed guidance in that filing. What you can expect to see in that is, beyond the safety and tolerability and PK, we will show the biomarker results that we are studying in that top-line readout. There are two biomarkers that we're looking at that are very helpful in the field of epilepsy. Those are transcranial magnetic stimulation and magnetic resonance spectroscopy. For those of you who know epilepsy, Xenon used TMS, which is the transcranial magnetic stimulation, to be able to help show that their drug was having a pharmacodynamic effect, which was XEN1101. It's a very similar strategy to what we're doing here with OV329. The parameters on TMS and MRS are different because we have a different mechanism of action and work on a different target, but they've been shown to be able to be good signs of clinical effect and target engagement. Essentially, what we will show, we have studied and gone through literature searches that looked at the first-generation medicine, vigabatrin. We know how vigabatrin works on certain parameters of TMS and MRS. If we're able to make directional movement on some of those same parameters, we think that's a pretty good sign that the drug is having the effect that we intend. We can also compare that against what a therapeutic dose of vigabatrin was. For a phase I study, we should be able to get out some pretty good answers to questions that will enable our phase II design. For anyone who really wants to understand those parameters in great depth, I'm happy to talk to you about them. I'm not going to go through the slide, but what we essentially in our design of the biomarkers looked very carefully at what are the parameters that vigabatrin worked on and why. We will look at those. We're studying those as well as a range of others. Through the MRS study, we'll look at levels of GABA increasing in certain regions of the brain. That would be a very good sign of target engagement. This is OV329. I'm very excited to talk about KCC2. One, because, as you heard us say, we are on track to be first in human this quarter. This is a very exciting target for the brain that until now, no one has been able to effectively drug and directly activate. We know that we have direct activators. Why KCC2 has been the great sort of white whale of neurology is because it has vast therapeutic potential. It is a precise mechanism of action, but it is downstream for many genetic causes of epilepsies and other diseases of hyperexcitation. What this enables us to do by directly activating KCC2, it is a master switch on neuronal hyperexcitability. When KCC2 is dysregulated, as it is in many different conditions, directly activating KCC2 should help bring a hyperexcited neuron and neural system back into balance. Essentially, it works by managing the chloride gradient within a neuron. In order for GABA to have its inhibitory strength and to keep neurons behaving normally, you need to have the potassium chloride gradient and neurons working well. What can happen when KCC2 is dysregulated is you get too much chloride built up in the neuron. You get a hyperexcited state. What KCC2 uniquely does is it extrudes chloride, lets the neuron operate in a healthier way, and that allows endogenous levels of GABA, the GABA that you already have in your brain, to work more effectively. We are very excited about what this could mean. It is central to maintaining GABA's inhibitory tone. What we like about this, as I said earlier, this is not just one program. It is multiple. We currently have four drug programs that are in active development. We know they are highly specific. We know that they are direct activators of KCC2. We have different formulation amenabilities across different programs. We've done phenotypic and disease model screens, so we have a good sense of how they may behave. Similarly to OV329, we haven't seen any sedation. This is a very ambitious picture, but it gives you a sense of the areas of where KCC2 direct activation may be therapeutically relevant. Now, clearly, Ovid is not going to target all these different conditions, but KCC2, because it is this master switch on hyperexcitability, has a lot of different therapeutic opportunity for patients and commercial opportunity for us. When you couple that with the point that I made a couple of minutes ago, that we have multiple programs that have unique characteristics, this gives us a lot of strategic optionality to explore co-development deals, other forms of partnerships, particularly in areas where the therapeutic potential might be different than what our historic experience has been within Ovid, which has been primarily more areas of epilepsy and hyperexcitability. The first program, this is the one that's going into humans this quarter, is OV350. It is highly specific. We know it directly binds. We know it is blood-brain barrier penetrant. The safety is very amenable. It's a very permissive safety package for us to go into humans. We're very excited by the therapeutic opportunity here because it behaves very much like an atypical antipsychotic, both in screening, phenotypic screens, and disease models. We've actually put it, and I'll show some of the data in a moment. We've put it in models. We've seen it be comparable to clozapine and act in a dose-dependent way. This was actually some of the early work we did. When we brought in the KCC2 library, because it works on neural hyperexcitation, we thought, of course, epilepsy. There is a lot of good data, actually, through OV350 in seizure models. However, we took a step back to really characterize the entire library in a more robust way. One of the findings that we were pleasantly surprised to arrive at was a phenotypic screen of this and other compounds in the library that essentially showed that KCC2 operated, and specifically this KCC2 direct activator, which is OV350, operates very much like an atypical antipsychotic. This image that you're seeing on the left is basically a screen. It's a phenotypic screen that compares against other reference products. It also screens for off-target and on-target effects. Essentially, the purple bars are telling you that it's behaving very much like an atypical antipsychotic. The little yellow bars are actually indicating it also has some anxiolytic properties. This was exciting to us. We've seen somewhat similar profiles for other programs in the KCC2 library. We never bet on a phenotypic screen alone. That's just a starting point. What we seek to then do is try to replicate and see other insights in disease models. The image that you see on the right is essentially a model that's commonly used for schizophrenia. They give PCP to animals. The green bar is clozapine. The gray bar at the bottom is placebo, and everything else is a dose of OV350. The net-net, you're seeing a dose-dependent response to OV350 in a psychosis model. As I mentioned before, the safety is very amenable. We expect to be dosing in humans in time and aligned with our guidance. Where we intend to go with 350, we'll be putting out more guidance in our filing. Knowing that it behaves very well in areas of psychoses, we're interested in taking it into a population that's very underserved, where we think we can have a very homogeneous population to study in a clinical trial. That is psychoses associated with Parkinson's disease dementia and Lewy body dementia. There is an approved regulatory path for that particular indication. There is an approved standard of care, but only about 12%-13% of patients respond to it. The hallucinations that those patients experience are signs of neuronal excitation. We think that there are some very good ways to study them and having a homogeneous population based on a skin tag and CSF that we can sample. We will be looking to do that. We will be taking a lot of the insights that we have from the phase I study that we're starting into patient trials. In sum, it is a really exciting time for Ovid. With With 329, we have a significant card turnover coming in the second half of this year with that biomarker and safety data. With KCC2, we will be the first, we believe, ever to be able to drug humans with a direct activator of KCC2. The safety and tolerability and PK data on that, as well as our exploratory biomarker, will be out by this time next year. Help us understand the opportunity in the class at the same time that we'll be introducing an oral into the clinic. We have the capital base to do that. Our capital currently goes into the second half of 2026, which is well in time for all those milestones and other answers that we'll be able to get from our pipeline program. With that, I will pause and maybe we can take some questions. Thanks, Meg. I'll kick it off with a question on OV329. There are different kinds of epilepsies that you could pursue for your indication. Given there are so many different mechanisms in development currently for different kinds of epilepsy, how are you going to select for the indication that you do decide to pursue later on for optimal success? Yep. We know the benefit of being a best-in-class and the next generation is we have a good sense of how the first-generation medicine behaved. With inhibiting GABA-aminotransferase, we know that it's very effective in reducing focal and generalized seizures. That's one important point. What we will look to do is look at a trial population that is, again, homogeneous, where there's significant unmet need in the field, and be able to take what we get from the phase I findings and translate it. Some of the things that we think next-generation GABA-aminotransferase inhibitor could be really good for would be for treatment-resistant seizures. As we know, there's still a tremendous amount of the adult population that are very underserved. 30% of them face drug resistance. Having novel mechanisms of action really helps there, right? If you're loading up on the same mechanism of action with different brands, that is probably not going to introduce a profound effect for those patients at that point of time. That's a very big market. Even a small penetration of a market that big is very significant. The other area where there's really high unmet need and a large treatment-resistant population is in developmental epileptic encephalopathies. Historically, that has been inefficient to develop in. We actually had done a basket trial years ago, and the FDA wasn't willing to accept a basket indication for DEEs at that point in time. They may be now. It seems like the regulatory posture is changing. Both of those are areas that would benefit from a medicine like OV329. Why do you think the FDA is now changing their mind about basket DEE trials? I mean, Lundbeck or Longboard is doing one, and Praxis might be also pursuing one. What do you think drove that change? Some of it might be a different team, but I think there's a case for looking at certain types of seizures and trying to be able to study the seizure type in a more homogeneous way and having that read through to different indications. I think once you get past a couple of DEEs that are larger populations, it then gets to be pretty inefficient to develop medicines there. If the risk-benefit is there to be able to develop more broadly, there is certainly a lot of patient need that would be hard to serve if the FDA made developers go out and do one DEE at a time, particularly some of the ones that are smaller orphan populations. And safety. I mean, with the FDA, it is all about safety too. If you have a safe mechanism of action, you have, I think, more flexibility to operate. Definitely. Any questions from the audience? Just curious. For OV329, you mentioned that it has a lack of Michael addition and it has a more selective enamine condensation for its activation. Just curious on how you think that might impact the intolerability profile of the drug. We haven't seen, so from a total tolerability profile in humans to date, but also in animals, we've seen a superb profile. Now, obviously, we have a higher dose cohort that we're running right now. Our profile in general has been very amenable. As I said, in humans, we haven't seen any signs of safety concern, no SAEs, mild AEs. No concerns from that or in the animal model work that we've seen to date, which has been pretty extensive. As you would appreciate, the question with 329 is less about will it work, because most people believe the mechanism should work. It's more of a question of establishing safety. We have put it through a very extensive battery of toxicology and other ocular safety characterization. Just curious, have there been any initial efforts on correlating PD activity like AUC or Cmax? Yes, we have been, yeah, doing that as part of drug development, as part of our normal. We have looked at that relative to the animal model data that we've worked on, and now we've been trying to correlate that as we've gotten human data in for our cohorts and see actually relatively nice comparability of what we can extrapolate from the animals into humans. I have a question on KCC2. You said that you were trying to target an indication that would be more homogeneous, but still have a high unmet need. Correct. Which would be PDP? Psychosis and Parkinson's disease, yes. Got it. Besides differentiating on safety, how do you think, based on the preclinical data you have seen, that it might drive a higher efficacy than what is available currently for these patients? Yeah. Unfortunately, and it's good that there is a standard of care, which there wasn't until as recently as 10 years ago. Unfortunately, right now, only 12%-13% of patients respond to pimavanserin. If you respond, you respond. Most do not respond. For those of you who know anyone who's had these forms of hallucinations and psychosis associated with PDP, it can be quite benign. These are actually patients who, with their caregivers, can tell you about the symptoms that they're having. They can say, "There's a dog sitting next to me," or, "Why aren't you talking to the guy on the couch next to you?" Being able to reduce even what are these benign, but still very upsetting forms of psychoses is significant for these patients. Particularly as the disease advances, they have oftentimes more concerns about security. It's a natural feature of this condition where there's more fear of home invasions, bodily safety, your home and family being threatened. Being able to address this, right, by trying to quell some of the hallucinations and moderate the psychoses would be very significant and profound for these patients. The challenge you have to also keep in mind, all of the atypical antipsychotics are almost contraindicated based on the other drugs that Parkinson's patients need to be on for the movement disorder aspect of their condition. There's not a lot of good therapeutic options for these patients, and it is very significant for the caregivers. In fact, it's one of the leading causes of hospitalization for this patient group. Awesome. Thanks for the color. With that, we are at time. Thank you all for joining us. Hope you have a good rest of your day here.