O-V-I-D. We cover Ovid Therapeutics with a buy rating and 12-month price target of $4 per share. It's my pleasure to introduce the Chief Executive Officer, Meg Alexander. Meg, it's a pleasure to have you with us today. Thank you, Ram. Happy to be here. For those in our audience who aren't as familiar with Ovid, this is a company focused primarily on neurological indications with a broad and diversified pipeline. What is particularly intriguing about Ovid is the nature and uniqueness of the targets that are being addressed by its various pipeline candidates. I think, Meg, it would perhaps be helpful if you could just take us through the most salient aspects of the Ovid pipeline as it stands today, and what the key defining characteristics are of the targets that Ovid has selected to target, and why they are important in neurological and neuropsychiatric indications. Thank you for that, Ram. I'd be happy to. You really set the story up well, in the sense that as we have built Ovid Therapeutics, strategically, there were some important things that we considered in terms of factors as we built our pipeline. One of those was the fact that we're focused on small molecules. That's what our team is good at prosecuting. We specifically went after what we consider to be universal biological targets in the brain. What I mean by that is we went after targets that have broad potential therapeutic applicability to disorders driven by too much neural excitation, basically put simply, when the excitatory inhibitory balance of the brain is not right. We were looking for biological targets that had breadth to quell that hyperexcitability across a number of indications. Importantly, the last piece, which you alluded to, Ram, was the fact that we went after completely differentiated mechanisms of action. Unfortunately, in the field of the CNS, for too long, we've been going after the same targets with the same mechanisms. Some of my colleagues across the field have done a really nice job of improving the pharmacology, starting to make medicines for the brain safer, easier to use, but nothing that's been really new mechanistically that's helped creating that step change for patients who don't have good solutions or who continue to have symptoms today. Symptoms like bad seizures and epilepsies, or forms of psychoses, like hallucinations and delusions. There just has not been enough novel innovation. As we built Ovid, we focused very much on differentiated mechanisms. We also felt that that was going to be a strategic advantage because we wanted to be enrolling trials where we weren't competing with two or three other companies that had the same mechanism of action, and we felt that if we were able to succeed commercially, we would have something truly differentiated and valuable. That indeed is what we've endeavored to do. I'll talk very quickly about the two different mechanisms across our pipeline. By the end of this year, we will have five programs up and running in the clinic, proof of mechanism or proof of concept studies. We expect actually four to five milestones in the next 12 to 18 months from those programs. They basically comprise a very exciting epilepsy program called OV329. That is in phase II right now, although we have a really interesting proof of mechanism, proof of signal biomarker study that'll read out around the end of this year. Again, completely novel mechanism for quelling neural excitation, and that essentially is a mechanism called GABA aminotransferase inhibition. Really simply, we inhibit the enzyme that eats GABA. GABA's the main inhibitory neurotransmitter in our brain. More GABA equals a quelled brain. We're developing OV329 for focal onset seizures, which is a busy category, but we believe we have a lot of good differentiation there. We're developing a pediatric formulation for two very intractable developmental epileptic encephalopathies called tuberous sclerosis complex seizures and infantile spasms. That's well known. We can talk more about the differentiators of that program if you want to, Ram. The other part of our pipeline, which has been earlier but is potentially very exciting because it may be transformational in the field of neurotherapeutics, and that is our program, which is KCC2 direct activators. KCC2 sounds a bit like a Soviet rocket, but it stands for Potassium-Chloride Cotransporter 2. It's a very important target in the brain for enabling, again, GABA, our main inhibitory neurotransmitter, to work. When this particular transporter is dysregulated, GABA can't do its inhibitory job. Essentially, the brakes in the brain can't work as they should. KCC2 has been really the great white whale of neurology and really neuropsychiatry because of its potential relevance across a number of different diseases and symptoms. The challenge is it's been a really hard target to drug until now. Now we've actually had two clinical stage direct activators. Our oral formulation, which we're really excited about because it can enable chronic dosing, is in the clinic being studied in humans actually right now as we speak, and things are going well. It will also, again, for that study, have a really exciting electrophysiology readout and essentially a proof of signal study that will read out around the end of this year. That's using something called ketamine and a ketamine challenge, but I can tell you more about that if you're interested in a moment. Lots happening at Ovid right now. I think the most logical place to start would obviously be OV329. For those in our audience who are not familiar, not only is GABA aminotransferase inhibition an interesting target, it's also a very well-validated one clinically and to a certain extent commercially, because there is a first-generation GABA aminotransferase inhibitor that has been brought through to the market in multiple territories called vigabatrin. In many ways, OV329 has built upon the key lessons of the vigabatrin program and vigabatrin's commercial history. Correct me if I'm wrong, OV329 was specifically designed by a very storied individual in the history of neuropsychiatry and neurology-focused drug development, an individual named Richard Silverman, who's a professor emeritus at Northwestern University. Who perhaps most notably is considered the key inventor of two very important neurological drugs, namely gabapentin, originally commercialized under the trade name NEURONTIN by Pfizer Inc., and LYRICA or pregabalin, commercialized also again by Pfizer Inc., for a wide array of neurological conditions. OV329 carries a number of attributes that are similar to those of vigabatrin, but also differs in key ways from vigabatrin, which should, correct me if I'm wrong, allow it to succeed everywhere that vigabatrin has, but also penetrate into areas where vigabatrin has not been considered advisable, even for clinical development because of its side effect profile, maybe elaborate on that just generally, then maybe take us through the salient features of the phase II program with OV329. Yeah. Thank you. That's a very good introduction to compound, Ram. OV329, you're right, does build on the work that was done with the first generation medicine, which was called vigabatrin, that was marketed by Lundbeck now many years ago. That has really been the only other GABA aminotransferase inhibitor in history. Why is that when it's a validated mechanism and we know that this works as an anticonvulsant? The why, of course, was that there was an idiosyncratic safety issue associated with the first generation drug. We had to do a lot of work over a lot of years. We had good reasons to believe that the safety issue was very specific to that compound and that it was not on mechanism. We had to do the work to prove that, which we've subsequently done with OV329. As a result, my ambitions for OV329 now are much greater than what we saw with that first generation medicine. Specifically, through the work that we've done to characterize OV329 to date, we believe fundamentally it will be a safe GABA-AT inhibitor, which is, of course, the minimum value proposition relative to that first generation drug. Drugs have to be safe. What's really exciting about OV329 is a couple factors. We have a therapeutic index because of the potency of OV329, thanks to the medicinal chemist, Rick Silverman, who helped us with this. That's far greater than that first generation drug. In different humans and models, we're anywhere between a few hundredfold to a thousand fold more potent than vigabatrin was. Gives us a wide therapeutic index to play with relative to that first generation asset. What that means is we're able to deliver inhibition, again, a braking system in the brain that we believe may be broader than what the first generation drug could do because we have better toleration. What that means is we're able to deliver GABA in the synapse, in the extrasynaptic region, hopefully creating more comprehensive inhibition in the brain, which may lead to better seizure reduction, which is so important because those are the initial indications where we're planning to take OV329. My great hope for it in terms of the opportunity and where we'll take it into phase II is that unfortunately in neurology, seizure medicines have been a painful trade-off of poor tolerability relative to efficacy. It's kind of like where cancer was 20 years ago. Too many medicines in the brain today work, but they sedate you, they give you headaches. There's collateral tolerability issues that come with trying to avert seizures and save your life. That's an unfortunate trade-off. With OV329, not only do we believe that we may be able to deliver more inhibition, and that's been suggested and demonstrated from our phase I study, where we were able to show that we did that relative to vigabatrin's past performance. Importantly, at this stage of development, OV329 looks to be a seizure medicine that has better tolerability than any seizure medicine that's marketed today or in development. That's a big deal because some of my colleagues and peers in this field are making what I think are going to be really good medicines. But the problem with epilepsy is, unfortunately, so many of these individuals have to take multiple medicines. Drugs can interact with each other. We really need new mechanisms today that work, that are safe, well-tolerated, and they're easy to take. That's what OV329 is appearing to shape up to be. We're taking it into a phase II trial, actually actively right now. That phase II program will be a traditional epilepsy study. We're going to provide more guidance on that in the next quarter associated with our filing. In addition to the phase II program, we're running a really interesting study called a photosensitivity study, which is essentially sort of a human assay or biomarker that helps us confirm that the doses we're taking into pivotal trials are anticonvulsant doses. We certainly have a lot of good biomarker data that suggests that they are. But this is more de-risking data that we hope to produce in the next six months while we run that phase II study, which we expect to read out around the middle of this time next year. Just to offer some additional context, clearly some in our audience will be familiar with older generation anticonvulsant drugs like lamotrigine or valproic acid or some of the racetams, et cetera. In effect, at the end of the day, if 329 winds up being all that you hope it is, it could conceivably be deployed in a lot of the same areas where these older generation anticonvulsants are deployed today and could offer a meaningful safety advantage versus all of those drugs. Maybe talk a little bit about the key lead indications that you're focused on with this candidate. Maybe also talk a little bit about how activity profiles in those indications have recently been attributed value by institutional investors. Historically, I believe in previous conversations we've touched upon companies like Praxis Precision Medicines and Xenon Pharmaceuticals. Certainly historically, specialty neurology companies like Supernus Pharmaceuticals have been active in the movement disorder space. Certainly with 329, you now have not only an opportunity, but certainly what appears at this juncture to be an undervalued one given Ovid Therapeutics's $450 million or so market cap. Yeah. I think for investors looking at Ovid Therapeutics, one, I think there's a tremendous opportunity. You heard me start the call saying we have four to five very significant milestones happening over the next six, 12, 18, 24 months across our pipeline. All of which I think should be very meaningful and potentially extremely de-risking and value accruing for our compounds. We are taking OV329 into indications that are the lowest risk indications, we believe, based on the underlying mechanism to the biology, and also relative to clinical risk. Those three indications are focal onset seizures, which I'll talk a little bit more about, tuberous sclerosis complex, as I mentioned before, and infantile spasms. Specifically, this mechanism of action has been well validated in patients in those indications already. They also are indications where counting seizure types and endpoints are reasonably hard relative to, and when I say hard, I mean clear, better to count, well-characterized endpoints that are accepted by regulators. Mitigates some clinical and regulatory risk, also helps provide the most direct line to underlying biology fit relative to the mechanism from what we know. That's also supported by many, many, many animal studies that we've run over a long time. I've seen OV329 work in more seizure models than I think any seizure medicine today, because we've run it in, I don't know, probably 12 or 13, where we've seen efficacy across them all. You were rightly saying that this mechanism that essentially allows more GABA in our brain, in the synapse, in the extrasynaptic region, has utility far beyond those three indications that I initially talked about. I want to take risk off relative to the next couple of years and where there's tremendous unmet need in those three indications that I mentioned. The applicability of this mechanism in OV329 in other DEEs, in neurodevelopmental disorders, even in pain, where I have very strong data, are all opportunities to grow this asset over time and to really lead the unlocking of this mechanism of action for the betterment of patients. That's the opportunity, and you asked a really good question, what are the sales relative to vigabatrin? It's important to know vigabatrin, because of the idiosyncratic safety issue with it here in the U.S., had a very serious REMS program and a black box. However, if we have a GABA-AT inhibitor that doesn't have that, we believe that 329 will be used earlier and longer, potentially unlocking big opportunities. Even with conservative assessments in focal onset seizures, which is an increasingly competitive indication, we believe there's easily a $1 billion worth of sales for OV329, even if you make extremely conservative assumptions about penetration, like 10% penetration. In the very rare but very disastrous pediatric epilepsies that I referred to, there's been no innovation. Pipelines are very dry, and unfortunately, the few drugs that exist are old, and they don't work in a lot of the patients. vigabatrin there was producing sales that peak at around $330 million in the U.S., not including the rest of the world. If you assume that that's a drug that was constrained to a very small number of patients, and you think about us being able to be used earlier, longer, and with more patients, I assume at minimum, we will double that just for the pediatric epilepsies. In total, I think OV329, just for where we're going right now, is potentially anywhere between a $1.75 billion, $2 billion opportunity. That doesn't include any indication expansion beyond that. Just to refresh our memory, in terms of the phase I target engagement and biomarker data, what would you say were the most important elements of this? You talked earlier about the width of the therapeutic index with OV329. Maybe give us a sense of the grounding that the phase I data provided that enables you at this juncture to be able to stipulate that OV329 does have a very wide therapeutic index and provides you with a lot of therapeutic indication and clinical development flexibility. Yeah. There were three factors with our phase I study that I think gave us a lot of insight and value that we were looking for. The first is that you don't take for granted with any drug early in CNS development, is that you're getting into the brain and having effect. We actually could see that we were elevating levels of GABA, the main inhibitory neurotransmitter, relative to participants who were just taking the placebo vehicle. That was one thing you never take for granted. That was good. We worked. Importantly, we knew that therapeutic doses of vigabatrin moved certain parameters, certain biomarkers in the brain that are measures of inhibition in the brain. We basically knew the goalposts that we needed to hit to show that we were having an underlying effect in the brain that was consistent with what happens when the first-generation drug was stopping seizures. We were able to show that with biomarkers, multiple biomarkers, in fact. Not only did we match the first-generation drug's performance and inhibition, we actually surpassed it on some of them. Again, really encouraging that we may actually have therapeutic utility that could be better than the first-generation drug, that we're asking and answering that question the right way now through phase II programs. Finally with OV329, we had modeled using five or six different streams of evidence, the level of exposure in the blood of the drug that we thought would correlate with therapeutic dosing. Essentially, the human data that we've now gotten correlates that very, very nicely, such that our dosing predictions appear to be right. When we get to that exposure in the plasma, we see inhibition in the brain in a highly statistically significant way. That's always a comfort when you're going into larger trials, that you've got multiple streams of evidence converging in the same place. Yeah. I think, with respect to 329, what our investor audience should be aware of is that this is a rapidly maturing asset, has multi-indication potential, and is very favorably positioned from a valuation standpoint relative to other candidates, other perhaps somewhat later stage assets in the movement disorder space, but that has the potential to be considered even more risk mitigated because of the precedent example of vigabatrin. In particular, as you mentioned, the REMS program, the safety issues with vigabatrin are well documented. There are heavy restrictions on vigabatrin because it causes visual field defects once you reach a predetermined cumulative dose. Having the absence of visual field defects with OV329 is a very important aspect and ultimately should position it very well. You can effectively follow in the footsteps of vigabatrin, but also break new ground with this asset. Let's turn now to OV4071, which is your lead candidate in the KCC2 inhibitor portfolio. I want to specify as a brief preface that this is a portfolio of assets aimed at a very unique target, which historically, as you mentioned earlier, has not been adequately queried or explored by other companies in the neurology field. By and large, Ovid is out there on its own innovating at the cutting edge when it comes to this target. There is applicability in both neurodegenerative disease and neuropsychiatry. Is that correct? Correct. The therapeutic potential of KCC2 is pretty profound. I think other strategic companies, big companies who have looked at this and tried to drug this target almost look at it as like a PD-1 like moment for the brain. Not in the sense it's not oncology, but in terms of what the therapeutic breadth of directly activating KCC2 may mean from not just those areas that you mentioned, but everything from neurological conditions like seizures and pain and epilepsies and the neurodevelopmental disorders you mentioned, to areas of psychoses and hallucinations like schizophrenia, Alzheimer's agitation, and hallucinations. The potential target is quite broad relative to symptoms of a number of different diseases, all of which are driven by too much excitation in different geographic locations, essentially in the brain. With respect to 4071, there are specific therapeutic area prioritizations that you've clearly laid out. For example, in the neuropsych space, we look at schizophrenia as being a very clean indication to go forward in because the approvability characteristics and requirements are very clearly demarcated. Those have been established over the last 10+ years in the context of atypical antipsychotics. The key primary efficacy endpoint outcome measures have already been clearly demarcated. That obviously provides you with a very interesting target opportunity, and clearly represents a significant total addressable market, and also an area of significant unmet need because it's well known that the atypical antipsychotics do not cure schizophrenia, leave a lot of symptoms unaddressed in schizophrenic patients, and often suffer from poor compliance, poor adherence, because they're very well associated with highly troubling side effects like akathisia, extrapyramidal symptoms, metabolic syndrome, weight gain, hyperprolactinemia. The list goes on and on and on. Maybe give us a sense of how you are thinking about positioning 4071 within schizophrenia and perhaps other neuropsychiatric indications as a whole. What your initial clinical development plan is within that context, and then maybe just briefly touch upon before we close your plans for 4071 in neurodegenerative disease, perhaps most importantly, within areas like dementia with Lewy bodies. Yep. It's a very good setup on the unmet need. Thank you, Ram. OV4071 is a very exciting molecule, and I don't say that lightly. In the areas of psychiatry, while the unmet need is as profound as what you've just described, Ram, unfortunately, the translatability of animal models historically have not been as good as we have had in other areas of the brain. With that proviso made, because that tells you a bit about the muster that my team and I need to see before we have confidence, before we take a molecule into the clinic and into humans. I have never seen data so consistent, so profound, and so confirmatory as what we've now seen with OV4071. OV4071, we know, is a direct activator of KCC2. It is a highly potent molecule. Again, really good safety margins on it. What's exciting about OV4071 is it appears that it may have a very significant impact on areas of psychosis and be a broad syndromic antipsychosis in psychiatry medicine. What I mean by that is at this point, we have probably 40 different models and experiments looking at genetic versions of schizophrenia, stimulant-induced versions, behavioral models. Some of these we run 10x over across different CROs. It's all telling us that we're having a very rapid and sustained effect in psychosis, the positive symptoms, but also negative symptoms associated with schizophrenia. We've seen the rescue of working memory, task switching, and essentially cognition or executive function, which is the holy grail, which unfortunately no medicine has really been able to do effectively to date. We have very good data specifically relative to schizophrenia. Where we're going next, we're in a phase I study right now. At Ovid, you can tell, we like to learn as much as early as possible to mitigate mid-stage clinical risk. We're running a broad battery of exploratory electrophysiology while we run the phase I, so we'll understand tolerability, safety, but we'll hope to learn more about how we're operating on certain translational biomarkers that we've established previously in our tool program and in animals. We're running something called a ketamine challenge. That sounds a little funky, but basically, it's extremely sophisticated electrophysiology using things like EEG to be able to see how we're moving neurotransmission in the brain relative to what we've seen from our preclinical studies. That helps us make choices about indication sequencing. From there, we're planning to launch a phase II proof-of-concept schizophrenia study, around the end of the first half of next year. What that electrophysiology will tell us, there's certain signatures on things like EEG that are highly relevant to Alzheimer's psychosis relative to acute schizophrenia. We can get a lot of information from this phase I study and the ketamine challenge to look at the potential attributes of how OV4071 is behaving in the brain. That gives us signals that if we see a constellation of movement on certain biomarkers that are moving metrics that are off, so to speak, in a sick person, and we're correcting them back in the right direction, starts to give us a confluence of data points and biomarkers say, "I feel comfortable going to this indication next." Because the opportunity with OV4071 beyond that schizophrenia proof-of-concept study could be, as I mentioned, Alzheimer's psychosis and agitation, Lewy body dementia, Parkinson's disease psychosis, and the list goes on from there. We're looking at, again, where is the data showing us the asset shines? Importantly, from human data, how can we make the best decisions about indication sequencing, given that this particular molecule may have very broad therapeutic use? Just in terms of what you anticipate are likely to be the most impactful value-driving catalysts and inflection points for Ovid. Are you thinking about this in terms of the phase II data with OV329? Are you thinking about this in the context of the ketamine challenge results with OV4071? Or ultimately, the data in the phase II proof-of-concept schizophrenia study with OV4071, which could come a bit later? It's all of the above. All of these are very significant de-risking and hopefully confidence-building moments. I think for investors who have not looked at Ovid, this is the time to do it. Each of those milestones over the next six, 12, 18, 24 months are going to be extremely meaningful to being able to lock significant value. I think if you look at some of my peers who have been successful, who have had perhaps one program that's anything like the five that I'm doing, the market has really rewarded it, and so has clinical use. I think this is the right time to look at Ovid for those who didn't, and the photosensitivity study basically tells you if you have an anticonvulsant drug. The phase II study tells you you got the right dose to go into phase II. Those are the two big things for OV329. That's 6 months away and 12 months away. The ketamine challenge, which will occur by the end of this year, essentially tells us that we're getting into the brain safely and moving things the right way. Hugely validating, keep in mind, for a target that large pharma in our field has wanted to drug for two decades. Big deal. Finally, a phase II proof-of-concept study is a very important value inflection time. That we'll have by the middle of 2028. Lots coming at Ovid. It's a really busy time for us. It's a great time to look at our pipeline if you haven't. Just two last things before we close that I figured would be important for you to delineate for our audience. Firstly, can you just recapitulate for us the length of the operational runway and whether that runs through, in effect, all of those value-driving inflection points that you just mentioned? Secondly, if you can offer us any insights into how you are thinking about potentially partnering or self-development, self-commercialization, even at this relatively early juncture. Yep. Thanks to the support of a great base of shareholders we have runway through all of those milestones that I just elucidated. We have cash runway into 2029. It covers all those trials that I just walked us through and all those potential value inflection moments. That's important. How we look at partnering. Partnering is in the DNA of Ovid. That's something that we have effectively done for a long period of time. It actually kept us from having to equity finance the company for five years. It's something that we do well. We also take very seriously in the sense that we think we have assets that have incredible value, and that value is not yet reflected in our stock to its most fulsome, I think, representation today. We'll look at value in the sense of, for OV329, this is a drug that has a lot of utility. We are running global trials right now. There is a day where working with a partner to potentially expand that into some of the other indications that I mentioned where it has utility could make sense. That's something we certainly would consider. On KCC2, this particular molecule, OV4071, may actually be what the field has been looking for 20 years, which will be a big deal if we're able to suggest and show that it does. So far, it's looking quite good. What that means is at some point, a company like mine that has good resources to do what we need to do but can't necessarily run five large-scale clinical trials at once across massive indications may come to a point where it makes more sense to work with a partner to unlock the value that may be inherent in KCC2 more rapidly. We look at that with clear eyes, but it's a trade-off because I'm completely uncomfortable with taking too much upside off the table for the company and our shareholders right now, and doing the wrong deal or a deal too early would certainly do that, I believe. We're open-eyed. This gives you a sense of the when and how we might look at things. We think we have a lot of value to unlock really in the next six, 12, and 18 months and want to be thoughtful to our shareholders about that. Meg, thank you so much for walking us through the salient features of the Ovid Therapeutics story. I'm sure our institutional investor audience will agree that this is a very interesting company. Now is clearly the time to begin looking at it if they haven't already. I think we're going to have to leave it there. Thank you so much for participating in our conference. Thank you to our audience for their attention. Thank you, Ram.