Episode 53: Sam Clark- CEO & Founder at Terran Biosciences

Have you ever considered the untapped potential of abandoned drugs? Join Dr. Sam Clark to discuss how his personal drive to combat mental illness is leading to breakthroughs in treatments for neurological and psychiatric diseases. Witness how Terran is not only resurrecting discarded medications for new purposes, but also pioneering the next generation of non-hallucinogenic psychedelic therapies aimed at tackling depression and Parkinson's psychosis.

First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder. Episodes launch weekly on Tuesdays. To view the full transcript of this episode, click here.

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Chapters

• 0:06 Revolutionizing Neurological and Psychiatric Disease Treatments
• 14:00 Teran's Role in Neuroscience and Therapeutics

Transcript

Speaker 1: 0:06

You are listening to First In Human, where we interview industry leaders and investors to learn about their journey to in-human clinical trials presented by Vile, a tech-enabled CRO hosted by Simon Burns, ceo and co-founder. Featuring special guest host Emma Moran, vp of CNS. In this episode, we are joined by Dr Sam Park, ceo and founder of Terran Biosciences. Join us to explore Terran's groundbreaking approaches, including psychedelic-based therapeutics and AI-enabled imaging software, revolutionizing the landscape of neurological and psychiatric disease treatments.

Speaker 2: 0:56

I'm Emma Moran, vice President of CNS here at Vile, and I'm really excited today to have Dr Sam Clark, ceo and founder of Terran Biosciences, with me today. So welcome to the First In Human podcast, sam.

Speaker 3: 1:09

Thanks, emma, it's great to be here. Thanks for having me on.

Speaker 2: 1:14

So, sam, can you share with our audience the pivotal moment or inspiration that led you to establish Terran Biosciences as a platform biotech company focused on transformative therapeutics for neurological and psychiatric diseases?

Speaker 3: 1:30

Sure. So it all goes back to when I was growing up. I had friends and family members who struggled with severe mental illnesses and dementias, alzheimer's disease, bipolar disorder and so I really wanted to better understand these disease and what was going on and develop better treatments, because I saw that the treatments that friends and family were being treated with just didn't work very well and they had side effects. And so I went and studied neuroscience at MIT and then I went to Columbia University where I completed my MD and my PhD. While I was in medical school I realized that, and I was really focusing in psychiatry, but I realized that the treatments that we had available they were still old therapeutics, therapeutics developed in the 1970s, 80s in old mechanisms, and they didn't work that well. And so I founded Terran with the goal of creating a platform company with a new way of developing neuropsychic drugs to treat both dementias and psychiatric conditions like bipolar and schizophrenia.

Speaker 2: 2:38

So neurological and psychiatric diseases, as you've just mentioned, pose significant challenges. Can you discuss how your pipeline addresses the unmet needs in patient care, especially in conditions where current treatments might have limited or suboptimal outcomes?

Speaker 3: 2:54

Oh, absolutely. Cns indications they're extremely difficult to treat and our understanding of the brain? It's still in its infancy, we still have a long way to go. For one example, there's over 3 million people in the United States with schizophrenia and yet there hasn't, as of now, been any new mechanisms approved to treat this disease. And there's also statistics that up to one in five people with homelessness suffers from a severe mental illness such as schizophrenia. These are very difficult diseases.

Speaker 3: 3:28

One of the ways we're addressing this is through a drug called idizoxan. This is a really interesting therapeutic that was previously developed for schizophrenia but had a number of what's called pharmacokinetic issues, had a number of issues where the drug would wear off too quickly in the body, that it was thought to be unfixable and so, while it was highly effective, development was stopped. We brought that back, fixed a number of those issues and it put it back into clinical trials. And then another way we're addressing this from a totally different perspective is through psychedelic-based therapeutics, where we have removed the hallucinations and removed the trip from the psychedelic through combination with another compound that's shown to be safe in clinical studies and removes the trip from the psychedelic, so you can get the benefits without the hallucinations, and we're developing that for depression. And then we have some other compounds we're developing for Parkinson's psychosis and then, lastly, we've developed this new software as a medical device to improve the diagnosis and essentially work up for Parkinson's disease.

Speaker 2: 4:38

Yeah, that sounds amazing, really interesting. The combination of traditional therapies with psychedelics is a unique approach really. How does your company plan to navigate regulatory challenges and societal perceptions while developing fixed dose combinations to address neuropsychiatric conditions such as Parkinson's psychosis and Taylor psychedelic effects, like you just mentioned?

Speaker 3: 5:02

Sure Happy to expand on that. So we take a unique approach to psychedelics First. We are developing the psychedelics with the longest histories of human use, the ones that have already been shown to be safe and effective. For example, psilocybin been shown to be safe and effective in clinical trials and have histories of human use spanning back thousands of years. The only issue there is you have the trip. Now, while the trip can be very beneficial to some people and we're not against the trip by any means it does limit the number of patients that could be treated in a hospital setting or an outpatient setting, as what we've seen with regulation is, if there is a trip, a doctor has to be present the whole time and that can take about six hours, from what we've seen in trials with psilocybin, and that means there's a limited number of patients who have the financial means to go in get that therapy for that six-hour session. Now this goes back to a discovery that was made in universities in Europe and in the United States. There are scientists that we know that psychedelics like psilocybin hit a lot of receptors in the brain. We also know that just one receptor, the serotonin 2A receptor, is responsible for the trip. What if we take a safe and effective psychedelic like psilocybin or DMT and we combine it with a second drug that's also shown to be safe and effective and that second drug blocks the 2A receptor, a highly selective serotonin 2A antagonist Block the first receptor, allowing the psychedelic to hit all the other targets in the brain but not have the trip. And by doing so, the data has shown so far that the mechanism of the psychedelic is fully intact and that this could be a take-home potential therapeutic to treat depression and other conditions without the trip.

Speaker 3: 6:54

Now with your question how do we navigate the regulatory landscape? Well, first of all, from a FDA perspective, that fixed-dose combination pass is a very well-defined pass that essentially follows a path where you have one active compound that has some side effect you don't want. You have a second compound that removes that side effect. You combine them together and that's a well-defined path that we're following that's been used with other drugs before.

Speaker 3: 7:20

And then from a legal perspective, of course, karen follows all the laws, uses all the proper licenses, but the legal perspective there is that this is a compound now that does not have a trip, cannot have a trip. The two compounds can't be unbound from each other, and so this could be a potential take-home therapeutic where it doesn't have the same legal repercussions or any of the side effects or potential dangers that come with an unsupervised trip. Again, we're not anti-trip, we're also developing psychedelics with a trip, but we think this will enable the widest population of patients to benefit who otherwise wouldn't have access, wouldn't have the time to take off from work to go have that trip, may not want a trip, may have religious or other reasons why they don't want to experience a trip. All of these people need access to care and we think by harnessing those aspects of the psychedelic for those patients, we can improve the access of who will be able to get this treatment and dramatically lower the cost of treatment.

Speaker 2: 8:21

So the partnership with Columbia University for an AI-enabled imaging software platform and recent FDA clearance of NM101 is fascinating. So how does this technology work and what potential impact do you foresee in the neuropsychiatric conditions like Parkinson's disease?

Speaker 3: 8:40

Well, first of all, we're extremely excited about the recent FDA clearance for our technology and this is the world's first FDA clearance for an MRI imaging software to measure a biomarker or to analyze MRI scans that are neuro-melanin sensitive. This is the first neuro-melanin sensitive MRI FDA clearance for a software to analyze neuro-melanin-sensitive MRI scans. Now the reason we're so excited is neuro-melanin is a compound that has been studied for about 20 years and well, actually discovery goes back longer, but it's mainly been the focus. Studies have gone 20 years and you've got over 500 patients that have been studied. There's over 50 clinical trials that have been done and this is a biomarker for dopamine in the brain and when all of us you know we have dopamine in our brains a little bit breaks down every day. It binds to iron and it forms this compound that you can detect on a standard MRI without any contrast, called neuro-melanin.

Speaker 3: 9:42

Now all of these different clinical studies have shown that neuro-melanin can provide potentially useful adjunctive information. What that means is, when a doctor is evaluating someone for Parkinson's disease or other neurological conditions, having access to neuro-melanin information is potentially very useful and neuro-melanin is lost in those conditions At the other side of the spectrum, in psychiatric conditions that are psychotic, like schizophrenia, where you may have psychosis. You gain additional neuro-melanin and the neuro-melanin becomes much higher than normal. And again, having access to that was shown in clinical studies to be potentially very useful, and there were even clinical studies that showed that having access to neuro-melanin information may help predict which high risk patients go on to develop full schizophrenia.

Speaker 3: 10:31

Now, despite all that, neuro-melanin was never FDA cleared and because there was no software that was capable of measuring it. So, columbia University there were scientists there, the lab of Guillermo del Horga and Clever Cassidy who developed initial algorithms that fully automated and enabled that measurement of neuro-melanin. We then licensed those algorithms in, built them into a full cloud-based deployable platform, submit it to the FDA for clearance and we recently got that clearance. So now, for the first time, doctors will be able to access that information as adjunctive of information as they make their evaluations.

Speaker 2: 11:10

Yeah, I was just going to say congratulations. That is really amazing. Thank you. So Teran has made its AI technology available for collaboration with various partners. Can you share some of the success stories or promising developments that have arisen from these collaborations and how do you envision the technology being utilized in, say, universities and treatment centers?

Speaker 3: 11:32

Sure, there's a couple of different things there. We have set up, for example, sponsored research with Columbia University. They're developing new algorithms, new applications, studying the software in new clinical trials. We also have a collaboration with the University of Ottawa and McGill University and they've used the software in different patient populations Alzheimer's disease and we envision these collaborations growing. We're always happy to collaborate with academic groups. We've gotten great data and Alzheimer's disease, schizophrenia, other conditions that the researchers there have been making great progress in all of these other conditions, and one of the other things is they've developed new ways to harmonize data across different scanners and just improve the software altogether. So they're doing a great job and we're very excited to collaborate.

Speaker 2: 12:21

Teran is a leader in the GMP manufacturing of psychedelic compounds and in the drug discovery and design of novel optimized compounds, so can you share insights into the challenges and opportunities that you've encountered in the psychedelic development space, especially with novel salts, polymorphs products and psychoplastogens?

Speaker 3: 12:43

So, yes, teran is a GMP manufacturer of psychedelics. Now, gmp just to define that, that's a good manufacturing practices, that's a set of regulations that govern the manufacturing of compounds used for human use. And Teran is, we believe, the largest, or if not one of the largest manufacturers of psychedelics in the world and we manufacture at scale psilocybin, LSD, mdma and other psychedelics and we provide these free of charge to licensed researchers and clinics who want to use them in their clinical studies. And it took us actually several years to ramp up this manufacturing to the capacity it's at now and we're also using it for our own clinical trials that are coming, and so we're very excited there. It was a challenge to get that all set up but we have a very good manufacturing team at Teran and it does a lot of these big GMP campaigns. And we've done that for our other drugs, like Ida Zoxan and the antagonists that we licensed. That removed the trip. We licensed those from Sanofi where they'd already been through multiple phase three trials in over 15,000 patients, and that's one of our exclusive partnerships with Sanofi. And then I think you touched on the discovery program.

Speaker 3: 14:00

Teran also has a big drug discovery program and we've created more new psychedelics, we believe, than any group in history, where last year we had approximately 40 medicinal chemists working on new psychedelics and we created new versions of a compound called DMT, the world's first orally active form. Orally active on its own, without combinations with MAO inhibitors or things that cause nausea and vomiting. We created the world's first long acting form of MDMA. We've created new forms of different empathogens meth alone, mbdb, mdai, mdea all these different derivatives that we think will have unique applications to patient care. We made breakthroughs on a compound called RMDMA. It's one of the mirror images of the molecule that we believe have less side effects than the other one. And then we've created what we call cycloplasogens, which are compounds that natively don't have any trip. That means they don't have to be combined with any antagonists. They don't have a trip to begin with, some next generation versions of ibogaine and DMT compounds that don't bind a receptor called the serotonin 2B, that's a receptor that's present in the heart tissue that may have some issues. So we have psychedelics that don't act at that receptor at all.

Speaker 3: 15:19

We've pushed forward on a number of other breakthroughs across the pipeline with new antipsychotics. Teran has recently entered the metabolic space. We're creating peptides that are new versions of basically, if you think of the drug ozempic, which has a lot of potential but has certain pharmacokinetic issues, we're working on new versions in that metabolic space that could treat diabetes and other conditions as well, with our drug discovery program. So we've been very, very active there. Teran has filed approximately 200 patents across the new psychedelic drug discovery and space for new compounds. So that, combined with our manufacturing, makes our very robust continual pipeline of breakthroughs and we'll be announcing some of our biggest breakthroughs later this year.

Speaker 2: 16:06

So, looking ahead then, how do you see to run biosciences contributing to the renaissance in neuroscience, and what role do you anticipate your company playing in shaping the future of therapeutics for patients with neurological and psychiatric diseases?

Speaker 3: 16:21

First of all, I just want to say I'm very proud of the team's accomplishments to date.

Speaker 3: 16:25

They've done so much building out new psychedelics, new psychopathogens, bringing Ida Zoxan back into the clinic, building out fixed dose psychedelic without the trip.

Speaker 3: 16:35

But there is a lot to do still and we see Taren's role as pushing forward these new discoveries, new breakthroughs, improving in areas that were previously thought to be impossible. That's partially due to our unique approach, which involves building teams of world experts around specific problems that people may think can't be done, like bringing back the drug that thought couldn't be fixed and we fixed it, turned it into a nice one-stay league the drug, ida Zoxan and other compounds. But one of the other things is, look, we know the patient is the most important stakeholder and we prioritize patients above any other priority at Taren and at the end of the day, the fact is that patients are suffering and so where we see Taren going is that look, we're not content to sit on the sidelines, just hope somebody else develops these treatments. So we'll continue to push forward, build out teams around these problems and keep making the new discoveries we've been making and bringing those compounds forward, and we have some big ones that will be announced later this year. We're really excited to play a role in this neuroscience renaissance.

Speaker 2: 17:43

Excellent. Well, thanks so much for your time and your thoughtful insights today, sam, and enjoy the rest of your day.

Speaker 3: 17:50

All right, well, thanks for having me on.

Speaker 1: 17:59

Thanks for listening. Youtube and Google.