Epilepsy Breakthroughs and Beyond with Jason Tardio and Toshiya Nishi from Ovid Therapeutics

**UPDATE** Since this episode was recorded, Takeda announced the results of the phase 3 soticlestat trials, which did not meet their primary endpoints.

We welcome Dr. Toshiya Nishi and Jason Tardio from Ovid Therapeutics. Dr. Nishi, with over 20 years of experience in drug discovery, discusses his role in the development of soticlestat and ongoing research on KCC2 activators for neurological disorders. Jason Tardio, Ovid's COO, shares insights on the company's focus on rare neurological disorders, including epilepsy, and its strategic initiatives for advancing treatments. Listen to their inspiring journey from the inception of Ovid Therapeutics to its current breakthroughs, and their perspectives on fostering a quality-driven and risk-tolerant culture in drug development.



https://ovidrx.com/


00:00 Introduction and Welcome
00:40 Meet the Guests: Dr. Toshiya Nishi and Jason Tardia
02:04 The Journey of Ovid Therapeutics
03:58 Discovering Saticklistat: A Serendipitous Breakthrough
08:35 Strategic Initiatives and Future Directions
13:48 Collaboration and Culture at Ovid Therapeutics
17:38 Ensuring Quality in Drug Development
21:50 Personal Insights and Closing Remarks
24:07 Conclusion and Farewell

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Music by keldez

Transcript

0:01

Hi there! Welcome to the From Lab to Launch podcast by Qualio, where we share inspiring stories from the people on the front lines of life sciences. Tune in and leave inspired to bring your life saving products to the world.

Meg Sinclair: 0:18

Hi everyone. And thank you for tuning in to from lab to launch podcast brought to you by Qualio. I'm Meg, your host, and I'm delighted to be here with you today. Before we dive into today's episode, we'd love it if you could take a moment to rate and share the podcast with your circle of science enthusiasts. And if you're interested in being a guest on the show, please check out the application in the show notes. Today, we're excited to be joined by two distinguished guests from Ovid Therapeutics. First, we have Dr. Toshiya Nishi. A veterinarian by training with over 20 years of experience in drug discovery and translational research at Takeda Pharmaceutical, Tashia played a pivotal role in the discovery https: otter. ai So it's a stat, a drug co developed with Ovid Therapeutics. Now as the Senior Director of Drug Discovery at Ovid, he's spearheading research on KCC2 activators, aiming to develop innovative treatments for neurological disorders. Sorry, Meg. I'm going to jump in and be the rude PR person. Um, it's, it's Saticklistat. Saticklist. It's almost like tickle. Saticklistat. Saticklistat. Okay. So I don't know if you want to do that piece over again. Okay. Ticlistat. Yeah, I can start from that sentence. Dr. Nishi played a pivotal role in the discovery of Ticlistat, a drug co developed with Ovid Therapeutics. Now as a senior director of drug discovery at Ovid, he's spearheading research on KCC2 activators, aiming to develop innovative treatments for neurological disorders. Also joining us is Jason Tardia, the Chief Operating Officer of Ovid Therapeutics. He has over two decades of experience in the biopharmaceutical industry, including leading with multiple sclerosis franchise at Novartis. We'll get into the inspiring story of Ovid Therapeutics, a company dedicated to creating life changing medicines for patients with rare neurological disorders. We'll discuss their journey from inception to launch and advancing the field of neuropharmacology. So let's get started. Welcome to the show, Jason and Tashia. for

Toshiya Nishi: 2:22

having me. Great. Can

Meg Sinclair: 2:25

you tell us a little bit more about how the two of you got connected and the story behind Ovid Therapeutics?

Jason Tardio: 2:32

Sure, I, I, I'll start. Um, uh, so Ovid's Therapeutics has been around since 2014. So it's nearly a journey of 10 years as a company. And the company, uh, was founded, uh, with a mission to dive into neurological, uh, research. At this time, Meg, I think it's important to understand 10 years ago, many companies were actually running away and divesting a number of their neuroscience programs. And so the founder of the company, a gentleman by the name of, of Matt during, uh, sought and saw an opportunity, uh, for a company like Avid to actually pivot towards, uh, neuroscience and specifically, uh, rare conditions, uh, of the brain. And so, uh, thus, uh, he, he formed a company initially around a medicine called Gaboxadol that he enlicensed, uh, from a company called Lundbeck. Uh, and the premise for that specific medicine. was that potential impact on a number of rare neurodevelopmental disorders. And so that product was, was, uh, studied in conditions like Angelman syndrome and fragile X syndrome as well. Um, during his time, uh, of, of, of starting this company, he was also looking to expand and diversify the pipeline. And, and, uh, he had, uh, relationships with a number of the key R and D executives at Takeda, uh, and through a meeting with Takeda. Um, he understood they had a discussion about a medicine called saticklostat, uh, that certainly Toshia can tell you a little bit more about, but a medicine that had been studied in a variety of different preclinical animal models within neuroscience, uh, and Alzheimer's, for example, and other conditions. Uh, and in some of these models, there was some clear signals about the potential for this medicine to be. an anti seizure medicine. It was suppressing seizures that would normally erupt in some of these animal models, specifically animal models of Alzheimer's. And so Takeda had an idea that this could be a nice anti seizure approach. They tested the medicine in a number of, uh, animal models of epilepsy, specifically Gervais syndrome, and it seemed to work, but they did not have at that time epilepsy experience. They didn't have rare neurology experience, and so it could have been just a serendipitous meeting of the two because Ovid was at this company focused on rare neurological disorders. Takeda had this asset that they believed could work in some of these rare epilepsies, but didn't quite know the approach to take, uh, and lo and behold, a relationship, uh, was, was started.

Meg Sinclair: 5:12

That's an amazing journey. Toshe, you played a critical role in the discovery and development of ceticlistat. What was it like to discover the potential? that it holds and how did that moment of realization feel for you as a scientist?

Toshiya Nishi: 5:25

Yeah, as Jason, Jason mentioned, it's a total serendipity, but first and foremost, uh, let me, let me, uh, note that, um, all the discovery works for Sotiklis that was done together while I was There that, that should be, uh, noted. Yeah. Uh, first, uh, first, uh, fir first of all, I, I, I would like to explain briefly about Cleta on its own. Uh, I'm, I'm, uh, tongue. I'm, I know by my tongue a little bit though. It is a small molecule inhibitor of enzyme called, uh, cholesterol 24 Hydroxy. Uh, another complicated name, though. It's an enzyme, you know, explicitly. Uh, um. It's expressing the brain, uh, you know, playing a role for regulation of a cholesterol metabolism in the brain, but this enzyme was not studied extensively as a drug target for many, many years ago. So, in a way, just discovery of sorticular set, uh, you know, small molecule inhibitor on its own is, is actually a serendipity. Um, uh, Uh, we then published a paper back in 2020 from the journal Scientific Report. Uh, we described how we ended up with, um, the discovery of anti epileptic property of, uh, Ceticlacet. Uh, that was, uh, that was a quite a bit of, uh, serendipity. As, as described in the paper, uh, So Tickle Asset was initially, uh, evaluated in an animal model of Alzheimer's disease. It was not a seizure model, but interestingly, uh, this animal model, I mean, it was a mouse model. Animals die suddenly, uh, in prematurity. I mean, it's a sudden death, so you never see, you never see, uh, how they die. But, you know, I was lucky or unlucky enough to see, uh, encounter a couple of moments of, uh, animal death. Uh, and, you know, they apparently die of seizure. And, uh, uh, actually I, I look, I looked up the literature and this particular, uh, uh, mouse model Alzheimer's disease is known for a high mortality rate. And lo and behold, we serendipitously realized that, uh, solace treated, uh, you know, animals had a few cases of, uh, you know, uh, you know, death and, uh, survival benefit. So that led us to a hypothesis of that. Uh, so Solace has a potential. Uh, to be a seizure medication protecting, uh, animals from, uh, dying from seizure, uh, that led us to the, uh, you know, series of, uh, studies, um, of CE in a whole bunch of different, uh, seizure seizure models. And that, that, that study was already published from, uh, journal epilepsy in 20, uh, 20. So, yeah, it's a, so Teta is, uh, you know, product of many, many Serre deities.

Meg Sinclair: 8:26

It is. It sounds very serendipitous, the journey to you two meeting together and, um, Stiklostat coming to be a treatment for epilepsy. Um, for Jason, given your background in the industry, what strategic initiatives at Ovid Therapeutics have you found most particularly impactful in advancing treatments for neurological disorders?

Jason Tardio: 8:47

Yeah, well, I can tell you what drew me to Ovid Therapeutics. Uh, I was Drawn to the company because it has a clear focus on patients, uh, and patients living with, at the time, you know, rare, uh, orphan related specific conditions, patients that had no pharmacological options. Um, And so for me, that mission around trying to find and bring some hope to these families and these individuals living with these conditions again in which they had nothing, um, spoke to my heart. And so that that's what drew me to to the company. Um, you know, avid. still has a very clear focus on developing medicines of high end needs, specifically in epilepsies and other seizure related disorders. Uh, but we also have a vision of expanding beyond that into, into, you know, more general brain conditions as well. And so the story in my five years here has evolved, as I mentioned, When I first started, we were clearly, uh, in, uh, a rare neurodevelopmental disordered company, uh, and in parallel, we had this program, Ceticlastat, through a partnership with Takeda, and we were developing medicine for a number of rare epilepsies or developmental and epileptic encephalopathies. Since then, we've evolved, uh, as a lot of companies do, uh, and, uh, expanded our breath a bit. So, again, we still have a clear focus on, on epilepsies, uh, but we've, uh, broadened our pipeline to largely focus on a number of small molecule, um, best in class first in class therapies that focus on a whole range of conditions. Our most advanced program is a drug called OV888, uh, slash GV101. This is a highly selective ROK2 inhibitor, uh, through a collaboration with a company called Graviton. We had identified a condition called cerebral cavernous malformations. This is a condition that affects Upwards of 1. 5 million individuals in the United States, they develop these raspberry like lesions within the central nervous system. Uh, and these lesions cause a whole host of symptoms, everything from seizures, which is why we got cancer. condition, but also headache, leg and arm weakness, etc. But also there's a very severe risk of these lesions, uh, hemorrhaging or bleeding. And if they do so, they can cause a whole host of downstream consequences. There's no approved therapies for this respective condition. Uh, and there's good biological rationale and good animal model data to support that. A highly selective rock to inhibitor like OV888 slash GV101 could have benefit. And so we're finishing a phase one for that respective asset, and we'll be announcing those results in the first half of this year in the next month or so. And we hope to move that into a phase two program later this year. Beyond that, we also have a program that's in phase one, ov329, which is a next generation GABA immunotransferase inhibitor. This is a validated approach to epilepsy. There's a first generation medicine called Vagabatrin that's quite effective in a number of refractory epilepsies, but it comes with, uh, an ocular toxicity signal. About 30 percent of patients develop, uh, visual field deficits. And so we believe our molecule of E3 to 9, a much more potent GABAminotransferase inhibitor, uh, could be dosed, uh, potentially, uh, at a much lower dose. You might not see some of the accumulation you see with the GABAtrin, and therefore we might be able to eliminate this ocular toxicity or adverse event. We're finishing up a phase one in the oral formulation of that, and we're also moving forward in IV formulation. We'll file an IND this year and hope to move that into a phase one program next year for status epilepticus. And then behind that, as Toshia mentioned, we have, and he's working very diligently on a library of compounds that are direct activators of the potassium. Chloride cotrans, cotransporter 2 or KCC2 channel, which is a channel specifically located in the central nervous system. This channel is implicated across a variety of conditions, everything from rare conditions like Rett syndrome, certainly epilepsies, but also even potentially more broad conditions like, uh, schizophrenia and psychosis. And so we believe we're the only company activators of this channel. We'll file a first IND later this year in the most advanced compound, which is a drug called OV329. Uh, and hope to get that into humans next year. So we've advanced our thinking, but we're still a company at our core that focuses on patients, as I've mentioned, focuses on conditions of high unmet need. Uh, and we're really excited about the programs that we're bringing forward.

Meg Sinclair: 13:39

I'm really excited to see all the things that you guys are pushing out and accomplishing this year. It sounds like a lot of exciting news coming out of it this year. That's great. It's a unique opportunity to have you both here on the show together in a perfect world. How should someone in an operations role and a drug development or scientist role work together?

Toshiya Nishi: 13:58

Yeah, absolutely. Yeah. I mean, as Jason introduced me, I am now spearheading, uh, you know, just drug discovery and preclinical development of KACC to activate a program. Uh, it's such an important protein, uh, regulating a fundamental mechanism of our brain. So, I mean, we are envisioning application of KCC to activate, uh, to a wide spectrum of brain diseases, uh, as, as he mentioned. Fundamentally, I mean, my discipline is pharmacology, which means identification and maximization of the therapeutic values of drug candidates, which is really, really interesting. I mean, I, I, As you, uh, introduced me, uh, I am a veterinarian by training. Uh, so this is where my, you know, uh, background as a veterinarian plays a role. Uh, in the veterinarian science course, you need to learn a lot of things. I mean, uh, many diseases and including even, uh, parasitosis, even a fish disease, all sorts of things, um, pathology and histology. Uh, that way, I mean, uh, we You know, I tend to, maybe I tend to see brain diseases slightly, uh, from a different perspective from other, uh, you know, uh, authentic neuro, neuropharmacologist. Uh, interestingly, in this industry, um, uh, most, most of the veterinarians, uh, Walk as a talk is called this, uh, but you know, I'm, I would strongly, you know, recommend, um, you know, a firm cozy as a, as a career opportunity for a veterinarian. Now we, we, we do have our own advantage to, to, uh, to contribute to, um, drug development.

Jason Tardio: 15:47

Absolutely. And Meg, what I would add there is, you know, look, we're a small company at Avid Therapeutics. We're roughly 50 employees, give or take, and so whether we like it or not, we're forced to work together very closely across all functions, and my role as the Chief Operating Officer, my job in a very simplistic form is to ensure that the company operates at an efficient level across all functions on a daily basis, that all of us are collectively marching towards the goal. Uh, accomplishment of the goals and objectives that the company has set forward. Uh, and so when we think about kind of Toshia and, and what he does, uh, and his team, and how some of my functions interact, I mean, clearly, uh, Toshia is driving a lot of our, our early research, but even early on in research and development, you need to be thinking about The end game, right? What is the ultimate goal? What is the condition that we could and potentially may want to address with these with these assets? Um, what's the opportunity? Um, what's that path? Uh, and and as you do this, you need a lot of insight and input across the variety of the functions of the organization. For example, The commercial function reports into me. And so one of the things you always have to ask is, all right, well, what's what would be the commercial opportunity if we brought this drug into X, Y, Z condition on everything goes smooth and we get this to patients, you know, what is that opportunity here? What does that return on that investment look like? And so you need to start thinking about these things early on. And so as a small company, you know, we do work very closely together. And I think that's one of the Positive attributes of a company like Avid is that because we're small, we're agile, we're flexible, but everyone is very close. And we, you know, we drive towards a similar goal

Meg Sinclair: 17:38

on that note of working all together and driving for that same goal here at qualia. We provide an EQS software companies for life science companies like yourself. So quality is near and dear to our hearts and mine, especially as our quality manager. So I like to ask executives, um, and scientists, as you're developing drugs to bring to market for patients, how are you ensuring a quality of culture on your teams?

Jason Tardio: 18:04

A quality of culture? Yes. Yeah. Quality of culture. Yeah. Well, look, I, I mean, culture should be embedded in a company. It should be in woven into the fabric of what a company does day in and day out. Um, and so. You know, culture can be defined as a lot of different things. The way that I personally define it, and then I'd love to hear Toshia's thoughts on this is, um, you know, culture is what is what you feel when you walk through the doors of an organization, right? How does, uh, the vibe of the company feel? How do people, as we've just discussed, collaborate and work together. How does how do people support one another? One of the things in the biotech industry is you take risks, you take calculated risks. Those risks more times than not don't work. How are we supporting one another? And, you know, extending a hand to pick someone up when maybe their experiment didn't work, but, you know, we give them a good pat on the back and say, look, what can we learn from this as we move forward? That's what culture is all about. Uh, and it, it also goes back a little bit to, one of the things I mentioned about what, what attracted me to Avid Therapeutics, you know, patient centricity, I think is a key part of culture as well. I mean, look, we'd be naive if we said here, and said that we, you know, we're, we're a non for profit. We are a for profit entity. We're a publicly traded company. So there is a business aspect to what we do, but I've always believed that if you put the patient first, you put the needs of the patient first, you drive forward drug development and then subsequent commercialization. with a specific laser focus and what's in the best interest of the communities that you're going to serve, that the business and the profits will follow. And so I think all of these are components of culture. I hope that answers your question. Toshiya, I'm sure you have thoughts.

Toshiya Nishi: 19:51

Yeah, absolutely. To me, I mean, as an R& D organization, uh, everything is down to risk tolerance. I mean, drug discovery, drug development is innately very, very difficult. But, uh, what we have as a, uh, what we should have a culture component to be successful organization. It's a, it's a, you know, a good balance of risk tolerance. Uh, indeed, I mean, in orbit, uh, corporate culture, we have a couple of properties. I would like to point out, be courageous. And be curious. I mean, these two are fundamentally important culture woven into the organization of orbit. Without that, I mean, we are often intimidated of doing, doing new things. I mean, Especially in my, in my, uh, uh, responsibility, I am working on, uh, you know, um, drops with new mechanism action, uh, which, which is quite challenging. Uh, but all of it certainly has, uh, uh, you know, uh, culture of encouraging to, uh, to not be afraid of risk. And of course we need to consider the risk and benefit balance, but this organization has a right set of mindset, you know, driving R& D, which is innately, uh, you know, high risk. Uh, that, that's, yeah, that, that is exactly, I wanted to come to all of it. This philosophy has been actually inherited from the founder of Orbit, uh, uh, as Jason pointed out, who is Mark Turing, who is super, super courageous. Uh, he was a fearless person, and he still remains an important role model. Uh, it's eternal role model in my, in my mind.

Meg Sinclair: 21:43

That's great. I love that. Be curious and be courageous. That's great advice, Toshiya. Um, well, our last question is more of a fun one. We like to ask each of our guests, if we ran into you at the bookstore at your local library, in which section would I find each of you?

Jason Tardio: 21:58

Ooh, Toshiya, do you want to go first?

Toshiya Nishi: 22:02

I, I like social science. I, I'm a scientist and I know, I mean, I like economics, uh, I actually, uh, subscribes to the, the economist, um, you know, I, I tend to see, you know, uh, anything happening in, in this world, uh, from a scientific perspective. I want to understand why this is happening. Uh, what is driving this? I mean, I'm not, you know, uh, I'm not a social scientist, but, uh, I always enjoy view, uh, all of, you know, difficult things happening today. But, uh, I always want to understand what is behind this. So, for that reason, I, I really love social science. Probably you, you will find me there.

Meg Sinclair: 22:47

Perpetually curious. Yeah,

Jason Tardio: 22:49

for me, Meg, I definitely skew more nonfiction than fiction and if I had to go through subcategories and I had to pick one, it'd probably be biographies. I love learning about people, their journey, how they've gotten to where they're at, the struggles they've had in life, how they've overcome those. Uh, yeah, I'm certainly 100 percent nonfiction versus fiction, uh, biographies, other historical accounts of, of events. I just, I love learning about history and people.

Meg Sinclair: 23:16

Always good lessons to learn from history. Well, thank you so much for sharing that little personal, uh, bit and your story at Ovid, thank you so much again for joining us and where can those who want to follow along with your journey, find you and connect.

Toshiya Nishi: 23:30

It's my pleasure. Thank you.

Meg Sinclair: 23:32

Yeah.

Jason Tardio: 23:33

Uh, so yeah, so for me, uh, yeah, obviously our website for, from a company perspective is, uh, uh, www. ovidrx. com, uh, and you can find me on LinkedIn at Jason Tardio, T A R D I O.

Meg Sinclair: 23:49

Great. Thanks Jason.

Jason Tardio: 23:50

Great. Thank you. Thank you both. Thank you. Bye now. Bye.

23:56

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