Ovid Therapeutics Q4 2025 Earnings Call - OV4071 clearance and clean OV329 7 mg data unlock pediatric expansion and extend runway

Angela, Conference Operator: Good afternoon, everyone. My name is Angela, and I will be your conference operator today. At this time, I would like to welcome you to Ovid Therapeutics Business and Pipeline Update Call. This conference is being recorded. All lines have been placed on mute to prevent any background noise. After the speakers’ prepared remarks, there will be a question-and-answer session. At this time, I would like to turn the call over to Victoria Fort. Please proceed.

Jay Olson, Analyst, Oppenheimer0: Thank you. Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release announcing business and pipeline updates and financial results for the three months and full year ended December 31, 2025. A copy of the release can be found in the Investor Relations tab on our corporate website, ovidrx.com. As a reminder, during today’s call, we’ll be making forward-looking statements. Various remarks we make during this call about the company’s future expectations, plans, and prospects constitute forward-looking statements for the purpose of the Safe Harbor Provisions under the Private Securities Litigation Reform Act of 1995. Forward-looking statements contained in this call are subject to a number of risks and uncertainties, which could cause our actual results to differ materially from those expressed or implied in such statements.

These factors include, but are not limited to, those discussed in our most recent annual report on Form 10-K and other filings with the Securities and Exchange Commission. Joining me on today’s call are Meg Alexander, our President and Chief Executive Officer, and Jeffrey Rona, our Chief Business and Financial Officer. Meg will go over the clinical and business updates we announced this morning, and then Jeff will detail our financial results, followed by a question-and-answer session. Before I hand the call to Meg, I would like to note that we are hosting today’s call in conjunction with the updates that we announced this morning in our earnings release. However, we do not plan to host regular quarterly earnings calls moving forward. With that, I’d now like to turn the call over to Meg.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Good morning, everyone, and thank you for joining us. This is a great morning for Ovid, and I’m keen to take you through both pipeline progress and business updates that we’ll go into greater detail with this morning. I’d like to start with our pipeline. Our good news is that we’ve now announced that we’ve received regulatory clearance for the first-ever oral KCC2 direct activator, which is OV4071. I want to thank our team who worked through the holidays to achieve this a quarter earlier than expected. In addition to that, this morning we announced that we now have safety and tolerability data associated with the 7-milligram dose of OV329, our next-generation GABA aminotransferase inhibitor. I’m pleased to share that there were no serious adverse events or adverse events associated with the 7-milligram dose.

All of our programs are advancing on track to patient proof-of-concept studies, and this is gonna mean exciting progress and potential readouts throughout the end of this year, throughout 2027. We also have new news in addition to that. We’re launching additional studies for 329. We’ll walk you through the data that gives us conviction. In addition to the programs that we already have in focal onset seizures, we’re launching programs today in infantile spasms and seizures associated with tuberous sclerosis complex. What has helped making this possible is additional capital that we also announced this morning through a PIPE financing that was led by Point72. I wanna thank that fund, as well as our top shareholders who have come in again to support us, including Janus, RA, Bellevue, Affinity, Coastland, Eventide, Adage, and Adar1.

With this capital, we will launch those programs in a way that does not compromise any of the other development programs that we’ve already discussed. Importantly, for our shareholders, the clearance of OV4071 also triggers a 30-day period for our Series A warrants. If those warrants are exercised, this will bring additional capital and potential proceeds to Ovid greater than $53 million. With this PIPE that we’re announcing this morning and the potential exercise of those warrants, Ovid will have a cash runway well into 2029. We’re excited to take you through all of this progress, which we’ll do in detail and answer questions. Before we do, I just wanna remind you what we’re trying to do and how we’re trying to operate to develop gentler, better medicines for the brain.

All of our programs are focused on controlling neural hyperexcitability. As you know, we’re pursuing fundamental biological targets to address that neural hyperexcitability. We do that by pursuing differentiated and what we believe are universal mechanisms of action through small molecule programs. Because at the end of the day, we want medicines that are easy for patients to be able to take. I’d like to acquaint you on our updated pipeline. What you’ll see is some of the programs that we’ve already been progressing in the clinic and the new ones that I just mentioned. Starting from the top, our program OV329 for focal onset seizures is progressing on track. As we said we would do this upcoming quarter, Q2 of 2026, we will be initiating a phase 2 randomized placebo-controlled trial.

Later this year, we’ll also be initiating an open-label photosensitivity study that will show us anticonvulsant response relative to the doses that we want to take into later development. I’d like to focus you on the green box that you see in the middle of this slide. These are the new programs that we’ll be adding as a result of the PIPE financing that we discussed this morning. Specifically, we’ll be taking OV329 into signal finding and safety studies, both for tuberous sclerosis complex seizures and infantile spasms. We’ll tell you more about the design of these programs in a moment.

Now, with the first-ever clearance of a KCC2 direct activator, OV4071, this upcoming quarter, Q2, we’ll be initiating a phase 1 study, and we’ll be running a ketamine challenge that will help us better characterize what we believe is broad antipsychotic activity associated with OV4071. For today’s news, we’re going to start with OV329, which let me remind you, we believe is a potential best-in-category anti-seizure medicine, which we think is appropriate as a treatment, not just for focal onset seizures, but also these very specific developmental epileptic encephalopathies that we’re discussing. I’m going to start today by telling you about the clinical progress we have with the 7-milligram dose.

This gives us even more conviction to open those proof-of-concept studies that I just mentioned in infantile spasms and tuberous sclerosis complex. What we believe of OV329 at this point in time is that it has a potential best-in-category profile. What do we mean by that? At this point, we know with 329 it is delivering inhibition in the brain and GABAergic inhibition both in the synapse and the extrasynaptic. We believe that’s leading to an optimal tolerability profile. We know that we differentiate from the safety profile of the first generation GABA aminotransferase inhibitor, which was called Vigabatrin, which had some irreversible safety ophthalmic issues. Importantly, this is a mechanism that is validated in focal onset seizures. We believe that we will have competitive efficacy. When it comes to patients, what’s important is we want a medicine that’s easy to take.

We anticipate in focal onset seizures, once daily dosing, very low dosing, and no titration. Let’s dive into some of the data that supports this program, because we know in focal onset seizures, while there are many medicines, there is still tremendous unmet need, with 40% of the community still uncontrolled with the existing mechanisms of action. Starting with the safety data that we have in hand, our 7-milligram dose in adults and healthy volunteers has demonstrated a very strong safety and tolerability profile. As many of you may recall, we ran the 7-milligram dose to expand dose optionality for our later-stage clinical trials. What the 7-milligram dose has now demonstrated is that we have no treatment-related serious adverse events. Additionally, across the entire SAD and MAD cohort, there were no adverse events associated with OV329.

It’s important to note there were adverse events in the whole cohort, but those were not associated with treatment. Some of the most common adverse events were things like cannula site reactions. Of course, there was also no ophthalmic safety concerns. Let’s take a deeper dive into this. Over the course of 329’s characterization in healthy volunteers, what you’re seeing in front of you is the adverse events that were reported that could be associated with OV329. These included, across various doses, headache, drowsiness, and metallic taste. All of these were very low in frequency. They were mild, and they resolved.

Importantly, relative to differentiation from the first generation GABA aminotransferase inhibitor, we have extremely rigorous batteries of visual testing as well as structural photography of the eye to ensure and to prove that we do not have the same retinal accumulation and dysregulation that was seen with the first generation drug. I can confidently say we have seen nothing associated with OV329. Of course, we will continue to run this battery of very rigorous testing throughout the entirety of OV329’s development because as we move towards registration, we want to be able to take to regulators a very deep armamentarium of patient ophthalmic safety data, because we want to avert the monitoring and the REMS that was seen with the first generation drug. All this is good news, but what makes us really excited as drug developers is what I’m about to show you next.

We have a lot of data that we leverage to inform our dose strategy with OV329. From a pharmacology strategy perspective, to achieve the inhibition that we seek and ultimately the anticonvulsant activity that we want to achieve for patients, our strategy has been to inhibit the GABA aminotransferase enzyme between about 50%-60%. In order for us to achieve that, there is a drug exposure level in the plasma that we have modeled, again, across multiple streams of evidence that are reinforcing to each other. You see that range in the middle bottom of this page here. It’s roughly 60 nanograms per hour per ml to 120. Now I’d like to point you to the right-hand side of this slide.

What you’ll see is the actual human data, and this is mean drug exposure in the plasma associated with each dose of OV329 that we’ve tested. Importantly, if you look where the green box is, you’ll see that both our 5- and 7-milligram doses deliver drug exposure in the plasma that should be consistent with the inhibition and potentially the anticonvulsant activity that we seek to achieve. Also importantly, we have linear PK as expected and consistent clearance. In addition to this, many of you may recall last fall, we read out the most expansive biomarker program that’s ever been done for a seizure medicine at this stage.

What that showed us across multiple biomarkers is that OV329 is not just getting into the brain, but it’s delivering cortical inhibition in a way that was highly significant and in a way that either matched or surpassed the levels of inhibition that were seen with therapeutic doses of the first generation GABA-AT inhibitor, giving us incredible conviction. What comes next? We have great confidence now that we have two doses that are within the exposure range that we predict to be therapeutic and that are extremely well-tolerated. They have shown cortical inhibition as measured by multiple biomarkers. At this point, we believe these are two strong doses to be able to take into phase 2 programs that in addition to being safe, well-tolerated, and delivering inhibition, we believe will also help optimize our responder rate.

I’d like to tell you more about our upcoming trial designs. As I mentioned, we are now launching 2 studies to demonstrate proof of concept in anticonvulsant activity for three two nine. Later this year, we will start an open label photoparoxysmal study. For those of you who are unfamiliar with this design, what it does is essentially allows us to demonstrate potential anticonvulsant activity in a population of patients who have a photosensitive form of epilepsy. We hope to have this data late this year. Why this is helpful is while we enroll a true gold standard randomized placebo-controlled phase 2 program, which will start next quarter.

This gives us, in the interim, anticonvulsant potential demonstration, again, giving us increased conviction and a potential de-risking event about the doses that we want to take into later development. For our phase 2 randomized placebo-controlled study, again, we intend to take 2 doses into that study, and this will be a traditional epilepsy study over 8 weeks to be able to demonstrate the key and traditional primary endpoints associated with seizure trials. This is very good news, and I want to thank our team for delivering this result. Now I’d like to turn to the new news, which is the pediatric programs that we’re adding. You’ve heard us talk about the adult capsule formulation of OV329, but we’ve long been thinking about expanding based on the data that we have in hand.

We have the opportunity to develop a pediatric and protected weight-based formulation to be able to serve the needs of these children and adults who remain very underserved. I’d like to take a moment to speak about that, starting with infantile spasms. Many of you may not have heard about infantile spasms because frankly, there’s been extremely little drug development in this area for the span of the last 20 years, and it’s needed. When these babies have an infantile spasm, which occurs between four to seven or eight months of life, it is an emergency. They have associated developmental disabilities, increased mortality, and the risk of lifelong epilepsies as a result of this. Despite the deep severity of this condition, there has been very little innovation.

Today, the current standard of care is Acthar Gel or other high-dose steroids as a first line, and Vigabatrin, that first-generation GABAT inhibitor, as a second line. Similarly, in Tuberous Sclerosis Complex, this is a genetic condition in which essentially children are born and form benign tumors or hamartomas across multiple different organs. But in this case, the one that we’re most focused on is the brain. People who live with TSC have high probability of having seizures. In fact, 80% of the community experiences them. Similar to infantile spasms, the standard of care is very limited for these patients. Despite that high frequency of seizures, the primary standard of care is Afinitor as well as Sabril, and those have limitations with how they can be used based on their safety.

In contrast to that, we think OV329 has tremendous potential and may even be disease-modifying. Why do I say that? If you look at the profile on the left, which we’ll talk through more, but then you look at the column on the right, in infantile spasms, we believe that there is an opportunity for 329 to be used first line with Acthar Gel and to be used longer to mitigate some of those developmental and epilepsy outcomes that we commonly see. We believe this because if you have a safe and well-tolerated and effective GABA aminotransferase inhibitor, clinicians will be comfortable using it earlier and for longer. Similarly, in Tuberous Sclerosis Complex, we believe that a safe and well-tolerated GABAT inhibitor could be used first line for seizure reduction.

Over time, because some of these babies are diagnosed very early, we may be able to build a path to possible prevention of seizures associated with TSC. We think this is hugely important. What gives us conviction beyond the data that we have in 329 from our own trials is that this is a mechanism that we know works. If you look on the left-hand column, the efficacy associated with GABA aminotransferase inhibition in these indications is proven. In fact, it’s been pretty profound. We’ve seen freedom from spasms, freedom from treatment failure in infantile spasms, and we see a high responder rate to those who respond in TSC, including a high degree of seizure freedom. Because of everything that you see on the right-hand side of the slide, Sabril is not used much today.

We think that the opportunity that exists is much bigger. When you look at this, what we’re showing you here is how the drugs that are used as a standard of care are prescribed for these indications. There’s a lot of information on these slides, but I’m going to mostly acquaint you to the right-hand side of the slide. What we see when you look at Sabril is it really underreflects what we think is the, not just the unmet need, but the market opportunity in these conditions. Sabril, as many of you may know, which is the brand name of Vigabatrin, was introduced decades ago. It was initially priced for a larger population epilepsy.

If you look across the middle row of these tables, you’ll see that it’s very limited in its treatment duration because the clinicians, and oftentimes the caregivers and parents, are concerned about using this for prolonged use because of its safety. Nevertheless, Sabril in the U.S. alone had peak sales of $320 million. We think, again, the opportunity of a safe version of this mechanism could be significantly bigger. This just gives you a sense of what’s giving us belief. If you look at the opportunity and the sales that were associated with Sabril, again here just in the U.S., we already have established a better therapeutic index with OV329 than what we saw with Sabril.

If you assume that we’re able to also realize ex-US sales, earlier in-line use, and this treatment duration, we believe that the opportunity for OV329, in addition to the opportunity that we are already pursuing in focal onset seizures, is very significant. We hope that this enhanced penetration duration will lead to very significant commercial opportunity. I want to quickly point to, we’re not going to spend a lot of time on this today, but we also have preclinical data that gives us confidence that these are the right indications to go to. In infantile spasms and focal onset seizure models, which is the distinctive seizure commonly seen in Tuberous Sclerosis Complex. We have demonstrated that OV329 is highly efficacious.

For those of you who have been following us, you know that we believe that we have a much safer version of a GABA aminotransferase inhibitor than what was seen idiosyncratically with the first generation compound. We have shown that in animals, OV329 does not accumulate in the retina and cause the retinal dysregulation that was the hallmark safety issue associated with Vigabatrin. We’ve looked at this now across multiple species. What this means in terms of the future of OV329, we think is quite bright. If you look at the past registration for OV329, we are continuing on with what we promised to all of you we would do with focal onset seizures with those studies that I mentioned. Importantly, we’re opening what we think is not just an opportunity for orphan status, but a very efficient path to registration.

The signal finding studies that we have in tuberous sclerosis complex will allow us to establish signal, safety, and step down and establish our pediatric dosing to inform both a signal finding study in tuberous sclerosis complex, but then also confirm the pediatric dosing that we will take into infantile spasms. We believe there’s an opportunity in both of these indications for a combined pivotal phase 2, 3 study, thereby enabling that efficiency to registration. As we wrap up the 329 section, we feel this is a strong win for our patients, for our shareholders, and our company. This is a completely additive clinical expansion program in de-risked indications. It allows us to do what we were doing before and create more value. What that means for our shareholders is you should anticipate more milestones and catalysts, both in the interim and in the long term.

We have the potential to develop these differentiated formulations to be able to protect and separate the IP and to consider the various commercial needs of both of these communities. At the end of the day, we believe this is going to enhance the value both for the program and for the company. This is great news. Again, I wanna thank Point72 and our shareholders for supporting us in this. I wanna take just a couple minutes at the end to tell you about the good news with KCC2, which we’ve been talking about for a long time, and the oral KCC2 direct activator is now here. Let us tell you what we’re on track to do. We have clearance in Australia. That’s important, as I mentioned, because it does trigger those Series A warrants.

After Australia, we will be immediately following in the U.S. and then the European Union. We are on track to initiate our phase 1 study this next quarter in Q2. That will be followed by a ketamine study later this year to show proof of mechanism, and we’re on track to start proof of concept patient studies late this year or early next year. I want everyone to know this is not the only KCC2 direct activator. We have an engine of discovery and further candidates coming beyond it, and we’ll be telling you more about that at a KCC2 day that we’ll be holding about a month from today on April fourteenth. We hope you’ll join us again for that. We’ll tell you more about that molecule at the KCC2 day.

Just to give you the highlights of what you should expect to see, we believe that OV4071 has broad syndromic psychosis applications. Just to point to that, we have forthcoming data that gives us conviction not only for the indications that we’ve talked to you about before, such as psychosis associated with Parkinson’s disease and Lewy body dementia, but additionally in schizophrenia and Alzheimer’s psychosis, agitation, and well beyond. I’d like to tell you just a little bit about OV4071 knowing that there’s more to come. We are very excited about the attributes of this molecule. As many of you know, we read out our tool program last year. We got a lot of great information about that program. This molecule is much better. We have a 20-fold potency. It’s highly active at low doses in a range of different animal PD models.

We have very strong brain to plasma penetration and no sedation’s been observed with OV4071. What I get really excited about with our team is that the pharmacodynamic data and armamentarium that is now mounting for OV4071 is robust. Across seizure models, psychosis models, pain models, genetic models of things like schizophrenia and Rett, we are seeing consistently GABAergic activity across all of these models associated with OV4071. What makes us also have conviction as we look at this data is that we are running OV4071 in comparison to marketed agents, both old ones and some of the new ones that have been recently approved. We’re seeing it perform very well across these battery of animal biological models. This is giving us conviction to advance into that phase 1 study, as I mentioned.

You’ll hear us talk about in April more about the KCC2 portfolio. If our thesis for KCC2 is right in terms of the opportunity of drugging this target, OV4071 will not be the only KCC2 direct activator. It’s a very good program, but we have additional discovery engines going on beneath this with further next generation chemistry, so that we will be the company that pioneers and unlocks the opportunity associated with KCC2. Why this matters, again, for those of you who have been following OV329 and maybe not as focused on KCC2, this is a target that is extremely important to the brain. It’s fundamental, and it’s a fulcrum to neural excitation and inhibition in that balance. These are highly precise small molecules that we’re developing.

The therapeutic potential is broad, as you heard me say, and we believe that these will be well-tolerated, and we know we have direct activators. We’re very excited to unlock this opportunity. What this means to our shareholders and our stakeholders is a really busy couple of years ahead. Just to give you a sense of what this means from a runway and a milestones perspective, my colleague, Jeffrey Rona, and I will take you through this. Just starting with the milestones, there’s a lot going on this page, but what you should pay attention to is the green arrows. Those are data readouts or major milestones. As we promised you we would do, today we’re reading out the 7-milligram data for OV329 in focal onset seizures. We will be initiating that gold standard phase 2 study.

We will also be initiating the photosensitivity open label study. We’re on track to read those out. We will be opening the programs that we said we would do today in Tuberous Sclerosis Complex and in infantile spasms. You’ll see that’s going to start with a signal finding and safety study and a dose confirmatory study with Tuberous Sclerosis Complex in an open label format. How we’ll be doing that, we’ll be starting with older TSC patients and stepping down into younger pediatrics. That allows us to establish safety and signal as we go. It will inform and de-risk our infantile spasms signal finding study. It also allows us to share our progress with you as we enroll enough patients. That will help, of course, inform the pivotal phase 2, 3 studies that I mentioned for each of these indications thereafter.

Finally, we are ready to roll with KCC2. This is what we’ve been waiting for. We will be starting that phase 1 study. As soon as we have enough of our PK and Cmax characterized from that phase 1 study, we will be initiating the ketamine challenge study. We’ll be doing that here in the United States. That will help us correlate electrophysiology along with potential clinical signs and symptoms. That will be important because it will help us not just support the initiation of a proof of concept study in Parkinson’s disease psychosis, but it helps us inform some of those other indications that you heard me talking about, including schizophrenia, which we have increasing conviction behind.

I just want to turn this over to my colleague and Chief Business and Financial Officer, Jeffrey Rona, who’s going to take us through the cash runway and what that means relative to the achievement of these milestones.

Jeffrey Rona, Chief Business and Financial Officer, Ovid Therapeutics: Great. Thank you, Meg. I will just briefly highlight our cash position. The full details of our financial results can be found in our fourth quarter and year-end earnings release issued this morning. As of December 31, 2025, Ovid had $90.4 million in cash equivalents, and marketable securities. As Meg mentioned today, we announced the PIPE financing with gross proceeds totaling $60 million before placement agent fees and offering expenses. We are grateful to our shareholders for their support as we continue to unlock the full value of our pipeline and programs. With the net proceeds from this PIPE, we expect that our cash runway will take us into the second half of 2028.

Assuming the full exercise of the Series A warrants triggered by the milestone we met with the clearance of the phase 1 trial protocol for OV4071, along with the gross proceeds from the PIPE financing, we expect that our pro forma cash runway will take us well into 2029. With that, I’ll turn the call back to the operator, so we can begin the question-and-answer portion of today’s call. Operator?

Angela, Conference Operator: Thank you. We will now begin Q&A. To join the queue to ask a question, please press star five on your telephone. Again, that’s star five on your telephone to ask a question. Please limit to one question before jumping back in the queue. Thank you. We will now pause a moment to assemble the queue. Our first question comes from François Brisebois. Please unmute yourself, and you can ask your question.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Frank, if you’re there, we can’t hear you.

Angela, Conference Operator: Looks like he has lowered his hand.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Okay.

Angela, Conference Operator: Our next question will come from Laura Chico with Wedbush.

Laura Chico, Analyst, Wedbush: Good morning. Thanks very much for taking the question. I was wondering if you could talk a little bit more about 329 and the visual monitoring. Meg, you mentioned you would kind of continue this through phase 2, but it sounds like the 7 mg data was quite clean. I guess just trying to better understand specifics on what you’ll be implementing during the placebo-controlled study, but also the open-label study. A quick follow-up, if I can squeeze one in. Thanks.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Sure. Yeah. Good morning, Laura. Great questions. Where we will be continuing the optic and the retinal monitoring is in the phase 2 study and then in the pivotal studies thereafter. The reason why is not because we expect to see anything, because frankly, we don’t. What we want to be able to have, as I mentioned, as we move towards registration, is a robust armamentarium of human and importantly, patient safety data that shows that we have not seen any structural changes in the eye, nor have we seen any visual changes. Frankly, this is well more robust than what Vigabatrin ever did in their REMS program.

We believe that we have a safe GABA aminotransferase inhibitor, and we want to hit the nail on the head when we take this to regulators and prove it, such that we don’t have to have some of the monitoring that has really limited the use of this mechanism in the prior first-generation drug. Laura, if you have a quick second question?

Laura Chico, Analyst, Wedbush: Okay.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: We’ll try to cover it.

Laura Chico, Analyst, Wedbush: Yeah, just briefly, the PPR study with OV329. I guess I just wanted to make sure, should we assume that a response rate should be similar to what we’ve seen with published studies on Vigabatrin? I know when you did the biomarker assessment, there were some nuances there, but just wanted to make sure I understood on the PPR study expectations there. Thanks.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Yeah. The way that we’ve designed the PPR study is that we want to be able to demonstrate anticonvulsant effect. We think in focal onset seizures, to do these studies the right way, it takes time to appropriately enroll them and get to an answer and of course, have an N size to be able to show anticonvulsant efficacy. We really like PPR studies, not just because it was used with older drugs, but frankly, our peer set, right? Other companies are using this right now, and it’s a good capital efficient and clinically sound way of assessing anticonvulsant activity in a patient population. That’s really our intention. It allows us to establish potential anticonvulsant activity at the doses that we want to take into later development. That’s the intention for us pursuing this program.

Laura Chico, Analyst, Wedbush: Thanks very much. Congrats.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Thanks, Laura.

Angela, Conference Operator: Thank you. Our next question will come from Marc Goodman. Marc, please unmute and you can ask your question.

Jay Olson, Analyst, Oppenheimer1: Hi. Good morning, everyone. This is Alyssa on for Mark. Thanks for taking our questions and congrats on all the progress. I was wondering if you could provide additional detail on the planned phase two design for OV329 in FOS starting next quarter, particularly around the key endpoints and what patient populations you’ll be targeting. Then separately, could you elaborate on the rationale for the ketamine challenge study for OV4071, and what you’re hoping to learn from the EEG and other biomarker data in the context of, the indications that you’ll be targeting? Thanks so much.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Thanks, Alyssa. Happy to. Let’s start with your first question, which is the phase 2 design for OV329. To address it is the population that we’re looking at is of course, adults with treatment-resistant focal onset seizures. That means by definition, these are seizure patients who’ve already failed a couple of anti-seizure medicines and continue to experience breakthrough seizures. What is helpful in the space of epilepsy is that we have extremely codified endpoints that have been effective and strengthened, because of the work of the Epilepsy Research Consortium, ourselves and our peers in the space. You know, there’s very good methods now for testing seizures, also balancing that relative to placebo rates. Some of the endpoints that are the endpoints to think about here, Alyssa, are, percent reduction in seizures, monthly seizure reduction from baseline. It’s also reduction in total seizures.

It’s the traditional endpoints, CGI endpoints, for example, the traditional ones that you would expect of a seizure study. We will be doing the same thing here. That’s important obviously to establish efficacy. In terms of the ketamine challenge, we get a lot of questions about this. The ketamine challenge has been used before also with other antipsychotic drugs in development. What we’re looking to do is, as I mentioned earlier, we’ll conduct a broad battery of electrophysiology. One of those things will include quantitative EEG, and we will also look at clinical discomforts and symptoms. We’ll talk more about this at the KCC today, and we’ll go in a deep dive at it.

At a high level, strategically what we’re looking to do is to be able to show that OV4071 is getting into the brain, that it is having an effect, that that effect is consistent with GABAergic activity, which would be on mechanism. There are certain bands and frequency bands that we look for that are also consistent with antipsychotic drugs in certain indications. If we’re fortunate, we’ll be able to correlate some of that quantitative electrophysiology with actual signs of clinical symptom amelioration relative to placebo subjects who are not exposed to OV4071. This would give us information to show we’re getting into the brain, we’re having an effect that’s on mechanism. There’s also some select biomarkers which we’ll tell you more about next month, that even help us have a read-through for indication identification and indication sequencing.

We think there’s a lot we can extract out of this. I think you can tell from our team we really like trying to use biomarkers to learn as much as we can early versus waiting for later development to ask and answer those questions.

Jay Olson, Analyst, Oppenheimer1: Excellent. Thank you so much. Congrats again.

Angela, Conference Operator: Thank you. Our next question will come from Myles Minter. Myles, please unmute yourself and ask your question. Myles is with William Blair.

Myles Minter, Analyst, William Blair: The open label photosensitive epilepsy study. What type of patient going to enroll in that study? I’m just aware that, you know, depending on the stimulus and then the underlying form of epilepsy, like the discharge patterns are quite different amongst those patients. I’m just wondering how much that will actually inform on focal onset versus something like generalized versus something like TSC infantile spasms. That would be really helpful.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Yep. We believe this is a good sign of broad anticonvulsant effect, Miles. We will be doing the study. As you may know, there’s not many sites in the world that do these studies. We’ll be conducting this at a very specialized site in the Netherlands who focuses on this. We’ll be doing it in adults who have diagnosed epilepsy, and we’ll be using the. Of course, the challenge is there’s not many patients in the world that actually have this form of epilepsy. But we’ll be basically selecting patients who have documented photosensitivity on prior EEGs. Those will have to be reproducible. We’ll be using screening using intermittent photic stimulation. What you can assume is we’re using that population to give us a general read-through, again, for anticonvulsant effect associated with their 5 and 7 milligram doses.

We believe that this is a modest and capital efficient way of being able to confirm anticonvulsant activity while, and before we have to wait for the full readout of the phase 2 program. It, it’s not necessarily the same thing, obviously, as a full phase 2 study. We recognize that. This gives us some de-risking data and again, more information that we’re headed down the right trajectory before we continue to spend more capital and also start to consider pivotal programs.

Myles Minter, Analyst, William Blair: Yeah. A quick one if I may, just on going after both prevalent population with FOS potentially generalized and then moving into TSC and IS on the rare side, how do you think about long-term sort of differential pricing, if that’s a consideration? Thanks.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: It’s absolutely a consideration, Miles. What we have the opportunity to do here with OV329 is, I think, to serve a number of communities that have really deep unmet need with differentiated formulations, where there will be true differences here. For the adult focal onset seizure population, as we’ve mentioned before, we’re pursuing a capsule. For the populations with infantile spasms and tuberous sclerosis complex, these are pediatric populations. We will be developing essentially a liquid or a syrup to be able to serve them. This is going to be weight-based dosing. It’ll be very different. There will be other differences I can say between the formulations that allow us to achieve the pharmacology strategy associated with these indications. That will allow us to have differential pricing relative to the communities.

Obviously, we’re doing so in a way that we think would be appropriate and responsible, and there’s some good analogs for this in the environment with other major developers that we’ve seen that we can point you to.

Myles Minter, Analyst, William Blair: Beautiful. Congrats. Thanks again.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Thanks, Myles.

Angela, Conference Operator: Thank you. Our next question comes from François Brisebois with LifeSci Capital.

François Brisebois, Analyst, LifeSci Capital: Hi. Can you guys hear me?

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: We can hear you now, François.

François Brisebois, Analyst, LifeSci Capital: Hello? Oh, great. All right. I don’t even know how to lower my hand, so not sure what happened. All right, well, congrats on everything. I just was wondering if you can touch a little bit more on Vigabatrin and the history here. You touched on peak sales, and maybe as you answer, maybe help us understand how like what kind of market size TSC and then the IS part of that is, and just, you know, when that visual issue came up with Vigabatrin, what was the impact on it? Just, like, color around, like how serious is the visual concern here? Thank you.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Thanks, Frank. When Sabril or Vigabatrin was first launched by Lundbeck, the field of epilepsy thought this was going to be a multi-blockbuster epilepsy medicine. The reason why is because it works so well as an anticonvulsant. However, it was determined post-market to have this preferential partitioning in the retina that in some patients led to blindness. It took the field, and frankly, it took us several years to demonstrate that this is idiosyncratic to that compound and to show that, of course, it’s not on mechanism. There’s a lot of evidence that we have that shows that now. What that means in terms of what the opportunity was, the sales of Sabril really understate where we think there’s both a lot of unmet need and also a market.

Because Sabril had that post-market safety finding, its use was very limited and constrained in the United States. Nevertheless, between the two indications, primarily infantile spasms, but also tuberous sclerosis complex, its sales peaked a couple of years ago at more than $320 million. You know, a drug that essentially can make children blind, that is only used in 6- to 9-month treatment durations for very limited use, peaked at that sales figure.

What we think, and in our conversations, most importantly with the clinicians who treat these children and these babies, is that if we have a safe GABA aminotransferase inhibitor, that the opportunity to use it earlier, to use it longer, can not only change the trajectory of the disease for these kids, but potentially may be a very large opportunity, and they would be much more comfortable using it for longer, hoping to improve those developmental outcomes. You asked one other question, François, that I wanna make sure we address, which was what was the breakout of sales. I’d love to be able to point you to that, but Lundbeck actually never broke out their sales by indication. That $320 million peak figure that I mentioned to you was in 2018. That included both of those two indications in the U.S. alone.

That doesn’t reflect Europe or worldwide sales.

François Brisebois, Analyst, LifeSci Capital: Perfect. Thank you very much, and congrats on all the progress.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Thank you.

Angela, Conference Operator: Thank you. Our next question will come from Madison El-Saadi with B. Riley.

Madison El-Saadi, Analyst, B. Riley: Hey, guys. Thanks for taking our questions. Congrats on the really comprehensive update here. Maybe starting with OV329. Did you say, maybe I missed it, how many patients in the 7-mg arm reached above the 80 nanograms AUC threshold, which is correlated with higher biomarker efficacy? Wondering if there’s any rationale to explore dose above 7 mg. Thanks.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Yeah. Superb questions, Madison. Thank you. The answer to your first question about how many were within the exposure range that we wanted to achieve, that’s a good and easy answer. All, 100%. With the 5- and 7-milligram doses, we have a lot of confidence that we’re in the exposure range that we targeted. The second question, also a super question, which is why not go higher? There is a reason. We know through all of our work, which is extensive now, but also looking at 30 years of Vigabatrin’s pharmacology, that there is a ceiling of how much inhibition of the GABA aminotransferase enzyme can be achieved in the central CNS, and that’s around 60%-65%.

When you consider that and you are well within, and in the case of our 7-milligram dose, above the drug exposure level in the plasma needed to achieve that, continuing to go higher doesn’t necessarily warrant the trade-off relative to what you may start to then take on relative to possible AEs, though we haven’t seen any of those, of course. We believe that we are well within the pharmacology strategy of being able to maximize the enzyme inhibition that should correlate with therapeutic activity. Our two doses are delivering drug exposure level that gets us there and of the 7 milligram that gets us over it and it gets all the subjects from our 7-milligram cohort over it, giving us again a lot of conviction behind these doses.

Madison El-Saadi, Analyst, B. Riley: Understood, Meg. That makes total sense. If I may, lastly, I just noticed you seemed excited to mention the KCC2 program. Looking towards the R&D day next month, will we see any additional pre-clinical data, maybe in AD agitation, please?

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: I would be in deep trouble with our chief corporate affairs officer if I tell you too much and scoop her for a month from now. What you will see is more pre-clinical data supporting biomarker strategy, supporting indication selection, and supporting the broad profile that we believe that OV4071 holds is, again, a broad syndromic psychosis agent.

Madison El-Saadi, Analyst, B. Riley: Got it. Thanks for doing this.

Angela, Conference Operator: Thank you. Our final question will come from Jay Olson with Oppenheimer.

Jay Olson, Analyst, Oppenheimer: Oh, hey, congrats on all the progress, and thank you for taking our question. How are you thinking about longer-term clinical development for three-two-nine in focal onset seizure after demonstrating efficacy in the treatment refractory population? Would you expand three-two-nine into development as a monotherapy in earlier lines of treatment? Eventually, as you look beyond focal onset seizures, do you expect three-two-nine to be studied in status epilepticus with an IV formulation? Thank you.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Thank you for the question, Jay. I think you’ve heard us and everyone at the team here at Ovid espouse our belief that OV329 and the inhibition of the GABA aminotransferase enzyme is a universal mechanism. We believe that safely elevating your natural levels of GABA in your brain, the braking system, has broad therapeutic utility in both seizures and epilepsies, but even in indications beyond that. I don’t want to comment too much further on long-term development planning. We’ve got plenty to do in the next two years, as you can see. What you can take away from this is that as we build more data behind OV329, much as we’re doing today, we will use the evidence to inform where we potentially expand and go next.

We absolutely believe that a safe and well-tolerated GABA aminotransferase inhibitor has a place across a lot of epilepsies, particularly if we continue to demonstrate what we think may be best in category tolerability, not just within the GABA-A mechanism, but potentially relative to the entire field of seizure medicines. Obviously, we need to continue to establish this with patients. If we do, we think this could have a very significant opportunity. As it relates to refractory status epilepticus, we have certainly pre-clinical data that would support taking us into those indications. There is a lot of unmet need there. With that said, from an operational and clinical perspective, those are very complex trials to run. I don’t think you should anticipate that we will be doing that in any time in the near future.

Just for the operator, I believe there’s one more question from our analyst at TD Cowen, Ritu.

Angela, Conference Operator: Yes. Our next question will come from Ritu Baral with TD Cowen.

Ritu Baral, Analyst, TD Cowen: Good morning, guys. Thanks for pulling me back into the queue. I wanted to ask about the first readout from the TSC study. There’s a pretty broad bar on your pipeline, Meg, and you mentioned that you were hoping to find early signal findings. Will those first signals out of 329 in TSC be at the 12-week timeframe, which I think is the primary endpoint of the pivotal phase 2-3, or will there be some additional dose-finding in there as well?

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Yeah, excellent questions. I don’t want anyone to walk away from this call thinking that you’re not going to hear anything about TSC until the middle of 2028, ’cause you will. You’ll hear things sooner than that. We’ve designed the tuberous sclerosis complex open label study very intentionally as an open label. There’s a lot that we hope to get from this that we will sequentially communicate around when we feel like the enrollment and the N size is big enough to have an answer that will give us all the evidence and sufficient evidence that we believe that we can make decisions and base information on.

What I mean by that, Ritu and colleagues, is that because this is an open label study, we’ve designed this to be able to start with older tuberous sclerosis patients, including adolescents, then going down to younger pediatrics before we initiate that infantile spasm study. Why we’re doing this is we want to, of course, establish safety in these pediatric populations. We’d like to be able to establish signal. Importantly, it allows us to confirm the dose modeling. We feel actually very confident based on the modeling that we already have internally with some of our animal models and our human data. We’d like to be able to confirm this with pediatric cohorts as we go. We have the opportunity to communicate about this throughout these open label programs.

In fact, we have a very similar approach with the infantile spasm open-label, as you see here as well. You know, again, this is a matter of as we enroll the study, we believe that this gives us the information we need. It also allows us to communicate with these communities, to give them the confidence that if we’re going to move into registrational trials, that we have an agent that may offer a benefit to the children.

Ritu Baral, Analyst, TD Cowen: Got it. Remind me how many patients were in the 7-milligram healthy volunteer arm? Oh, I think I believe it was 11. Are you surprised that it was so clean compared to the prior doses? You know, what, if anything, does that tell you about how you expect both doses to behave from a safety perspective going forward?

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: You did answer the question for me, but I’ll just reinforce what you said. It was 11 in the SAD/MAD cohort that were taking the 7-milligram dose of OV329. You know, at this point, we’ve had, I think, nearing 70 people throughout the phase 1 study. We’ve had a goodly number of healthy volunteers be now treated with various ascending doses of OV329. In terms of the tolerability, I’m not surprised. This is on mechanism for we believe some of the differentiators of OV329. Importantly, it would be one thing if we just had this tolerability and safety data and didn’t have the biomarker data that we have.

We have the benefit now of not just knowing that OV329 is getting into the brain at these doses, that it’s elevating levels of GABA in the medial parietal lobe, that it is driving cortical inhibition that’s known to be the mechanism that exceeds or is commensurate with that of what we’ve seen with therapeutic doses of Vigabatrin. We’re also seeing exposure increase by dose as we predicted and expected. We feel very good that these are doses that are doing what they need to do in terms of the pharmacology strategy while also having that tolerability. Just, you know, for those who are newer to our story, 329 is designed to not only be safer but well-tolerated. Unlike the first generation drug Vigabatrin, OV329 delivers GABA in the synapse and in the extrasynaptic region. These are called forms of phasic and tonic inhibition.

Why does any of that matter? It matters because Sabril only drives or Vigabatrin only drove GABA in the synapse. Similar to other drugs, like benzodiazepines, for example. What happens when that occurs is when you flood the synapse with GABA, you hit synaptic GABA-A receptors. That drives a lot of tolerability issues like sedation and other. But because OV329 has this broad therapeutic index that the first generation drug did not have, we’re able to deliver this phasic and tonic inhibition, essentially coating the entire neural environment in a more inhibitory milieu. It’s less of this surge that you see with other drugs, and it’s a more cooling down of the ecosystem around the neurons. We believe that that’s leading to a better tolerability profile.

What we’re excited to go ask and answer next is will it lead to an even better efficacy profile? That’s why we’re running the studies that we’re running.

Ritu Baral, Analyst, TD Cowen: Great. If I could squeeze one last one in just about your FOS and your PPR study. As you look at those efficacy endpoints, which I believe are a percentage change of certain EEG thresholds, do you believe that those changes in the PPR model, I mean, as we compare it to. Well, first of all, is there a target that you guys are looking for in those EEG markers? Second, is a PPR response proportional to ultimate seizure response? Basically if you end up with stronger PPR data, is it indicative of potential stronger seizure reduction?

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: The way that we have looked at designing this PPR study is we feel that it gives us conviction about the doses and conviction of anticonvulsant effect. I think truly to see what the anticonvulsant profile is of OV329 is why we’re running the phase 2 study that we’re running, right? A true randomized placebo-controlled trial. But just from an endpoint perspective, what we’ll be looking for in photosensitivity study is three key points to be clear. We’ll be looking at reductions in the number of IPS frequencies that induce the PPR, the photosensitivity response. We’ll be looking for the threshold frequency to induce these photosensitive responses, and we’ll be looking also at complete suppression of these photosensitive responses, both during and post-dose. We think, you know, this will give us some helpful information.

It’s not the same thing as a pivotal or a phase 2 study. While we do the full phase 2 study, I think it gives us confidence-building and de-risking data that enables us as we continue to expand the life cycle and the broad opportunity of OV329 to continue to make those investments and to robustly pursue the value creation opportunity associated with this program. This concludes our question.

Ritu Baral, Analyst, TD Cowen: Great. Thank you.

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: Thank you.

Moderator, Call Moderator: Sure thing. This concludes our question and answer session. Meg, any closing remarks?

Meg Alexander, President and Chief Executive Officer, Ovid Therapeutics: I just wanna thank everyone for your time this morning and for your continued interest in our company. I wanna thank Point72 and our shareholders who supported us in today’s news. We’re really pleased with this progress across the pipeline and the business, and I wanna just take a moment to thank the patients, the caregivers and parents who are advisors, the doctors and clinicians who are our partners, and I really wanna thank our team here at Ovid. They made it possible. They worked through the holidays in order for us to deliver early on some of these outcomes. Thank you all for your support. Keep watching us, and we’re gonna work to deliver.

Moderator, Call Moderator: Thank you for joining. This concludes today’s call. You may now disconnect.