Ovid Therapeutics Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Thank you to the team at H.C. Wainwright & Co. for hosting us. I am Meg Alexander, and I am excited to tell you about our progress at Ovid and our mission to pioneer better, gentler medicines for brain conditions. We are a forward-looking company, and we will be making forward-looking statements. At Ovid, I opened with saying it is our mission to create better, gentler medicines for the brain, and there are very unique ways in which we do this. We decided years ago, looking out at where neurology was, that unfortunately, it was a sea of sameness. What do I mean by that? We were seeing a lot of companies and developers go after targets that we already know with mechanisms that we already know work. While that is good, we always want better pharmacology and incrementally better medicines. We did not think this would really be a step change for patients.

We went out to go after fundamental biological targets that drive too much excitation in the brain, neural hyperexcitability. We specifically went out to find programs and mechanisms of action that were completely unique and that we thought would have more universal efficacy, broad therapeutic utility. Finally, we have been doing that with the hope that if we deliver these novel mechanisms for fundamental targets in the brain, that we may have first-in-class and best-in-class medicines that would really bring that step change to patients. That's where we are. We're a clinical stage company today, with a desire to be fully integrated, and we have 4 to 6 proof-of-concept milestones coming out over the next 6, 12, 18, and 24 months. This strategy has helped us build a pipeline. Can you Team? There we go. Whoop. The pipeline that you will see in front of you momentarily, that looks like this.

As I mentioned, we're a clinical stage company, and we have two very unique mechanisms that we're progressing in the clinic. One is a program called OV329, and I'll tell you a little bit more about this mechanism. This is designed for a set of very intractable epilepsies, including focal onset seizures and very devastating pediatric epilepsies, including tuberous sclerosis complex and infantile spasms, and potentially others over time. These are advancing in signal finding and phase II proof-of-concept studies as we speak. We'll tell you more about that. Below that, in the purple part of our pipeline, you see what is the beginnings of a very novel and exciting franchise of direct activators of a target called KCC2, which stands for potassium-chloride cotransporter 2.

This has been the target that many have wanted to drug in the brain for decades because it's highly implicated in diseases and symptoms that are driven by too much excitation of neurons, but it's been really hard to do until now. We now have the first oral KCC2 direct activator in the clinic. I'm very excited by this molecule. It appears to have very broad therapeutic utility across a number of different conditions and symptoms of the brain. But first, we'll go ahead, and we'll start with the epilepsy program. That's OV329. The field of epilepsy is having more medicines come to the fore. That's great news for patients, and hopefully better medicines at that. Though, unfortunately, the holy grail of a seizure reduction medicine has not yet been achieved.

When I say that, what I mean is we want medicines that work to deliver anticonvulsant efficacy, that don't make you feel bad, so they're safe and well-tolerated, and that they're easy to use and take, which unfortunately, despite a lot of innovation and a lot of progress by my peers, the field hasn't been able to achieve that yet. OV329 appears to be the drug that will do exactly that. It's highly potent. It's a validated mechanism, but only one drug tried to drug this target before, and that first-gen drug had a unique compound-specific toxicity that we were able to rationally design around.

If we do this and have both the efficacy, potency, and the superb tolerability that this medicine appears to have today, we believe this will be a very big opportunity, not just in focal onset seizures, where there remains tremendous unmet need, but also in developmental epileptic encephalopathies, which are very severe pediatric disorders, and also where we know this mechanism of action that OV329 has is validated and has delivered profound effects. This really could be a game changer for many children and adults. We will talk about how it works. Whoop. It is a relatively simple mechanism of action. GABA is the main breaking system in our brain. It is the primary neurotransmitter and the primary inhibitory neurotransmitter. When it cannot be functional, that is when we start to see seizures and other conditions.

What OV329 does, it essentially inhibits the enzyme that catabolizes or that eats GABA. What that means is we get more GABA, both in the synapse and spilling over into the extra-synaptic region, allowing the breaking system in our brains to work as it should. Because we rationally designed OV329 to have an improved therapeutic index, we are able to do this and deliver GABA around the neurons in a more inhibitory neural environment better than many other medicines have been able to do. All of this is seeking to solve a problem that we have known has existed now for many years. That is, there was another medicine that tried to approach this mechanism of action. It was called SABRIL, and it was marketed by a company called Lundbeck for many years. There is a lot we could learn from that.

Specifically, we could learn that it worked as an anticonvulsant mechanism, but that drug, developed 40 years ago, was like a lot of drugs developed 40 years ago. It came with a lot of baggage. It did not have the same level of sophisticated pharmacology that we have today. As a result, this drug had a very unique toxicity in the sense that it accumulated and partitioned in the retina and led to, ultimately, a type of irreversible tunnel vision. Not okay. We want to save the brain from emergency seizures, but making people blind in so doing is not copacetic. We have completely designed around that with OV329 through very focused chemistry as well as pharmacology. In fact, we went to the same fellow who developed LYRICA now many years ago to help us design OV329. We have since done that.

We have a thousandfold potency difference, binding nuances, but the most important factor is we have run the killer experiments, many of which, and we know that our drug does not partition in the retina like the first-generation drug did. We have a safety profile and what appears to be a tolerability profile that looks better than any seizure medicine in development or marketed today. We believe OV329 is going to be a drug. The question is: is it a good drug, or is it a great drug? We are asking and answering that in a phase II study and also a photosensitivity study right now. One of the reasons that gave us a lot of conviction is the nice thing about the way technologies are moving in epilepsy is you can almost run a phase II study in phase I right now.

What I mean by that is the technology allows us to look into the brain and see, are we restoring the braking system in the brain when we give healthy human volunteers our drug? We were able to do exactly that. Actually, this time last year, we read out results from a phase I study. We used a broad battery of basically electrophysiological biomarkers. In some, what it told us is that we were getting into the brain with OV329 at our desired clinical doses. We were increasing inhibition in the brain. What was really neat was that we were able to compare it to therapeutic doses of that first-generation drug I mentioned a few minutes ago. We were able to definitively show that we are not just matching, but we are actually exceeding the level of inhibition that that drug delivered in the brain.

Good sign when you have seizures and your brain is overactive, too much hyperexcitability, a good sign that we were delivering what would likely be therapeutic efficacy. That's exactly where we are now. Importantly, safety obviously is a big thing when you're trying to replace a first-generation drug that had baggage, and significant baggage. We've been able to characterize our drug at clinical doses, OV329, and two important takeaways. If you look on the left, there's a lot of numbers here, but what this is saying is this is so far the safest, best-tolerated drug that we've seen in seizure medicines, period.