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.
Emma Moran: I’m Emma Moran, Vice President of CNS here at Vial. I’m excited today to have Dr. Sam Clark, CEO and founder of Terran Biosciences with me. Welcome to the First in Human podcast, Sam.
Sam Clark: Thanks, Emma. It’s great to be here. Thanks for having me on.
Emma Moran: 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.
Sam Clark: When I was growing up, I had friends and family members who struggled with severe mental illness, dementia, Alzheimer’s disease or bipolar disorder. I wanted to better understand these diseases and what was going on and develop better treatments. I saw that the treatments my friends and family were being treated with just didn’t work very well. They had side effects.
I studied neuroscience at MIt. I went to Columbia University where I completed my MD and Phd. While I was in medical school, I focused on psychiatry, but I realized that the treatments we had available were still old therapeutics developed in the 1970s, 80’s. Old mechanisms. They didn’t work that well. I founded Terran with the goal of creating a platform company with a new way of developing neuropsychiatric drugs to treat both dementias and psychiatric conditions like bipolar and schizophrenia.
Emma Moran: 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?
Sam Clark: CNS indications are extremely difficult to treat. Our understanding of the brain is 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.
There’s also statistics that say up to one in five people with homelessness suffers from a severe mental illness such as schizophrenia. These are very difficult diseases. One of the ways we’re addressing this is through a drug called Idazoxan.
This is a really interesting therapeutic previously developed for schizophrenia but had a number of pharmacokinetic issues. The drug would wear off too quickly in the body. It was thought to be unfixable. While it was highly effective, development was stopped. We brought that back, fixed the number of those issues, and put it back into clinical trials.
Another way we’re addressing this from a different perspective is through psychedelic-based therapeutics where we have removed the hallucinations and trip from the psychedelic through a combination with another compound shown to be safe in clinical studies. You can get the benefits without the hallucinations. We’re developing that for depression. We have some other compounds we’re developing for Parkinson’s psychosis.
Lastly, we’ve developed this new software as a medical device to improve the diagnosis and essentially work-up for Parkinson’s disease.
Emma Moran: The combination of traditional therapies with psychedelics is a unique approach. 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 tailor psychedelic effects like you just mentioned?
Sam Clark: 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 has 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 (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. What we’ve seen with regulation is if there is a trip, a doctor has to be present the whole time.
That can take about six hours from what we’ve seen in trials with psilocybin. There’s a limited number of patients who have the financial means to go in, get that therapy for that six-hour session. This comes back to a discovery made in universities in Europe and in the United States. where scientists posited, “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 [00:05:00] antagonist blocks the first receptor, allowing the psychedelic to hit all the other targets in the brain, but not have the trip. By doing so, the data has shown so far that the mechanism of the psychedelic is fully intact. This could be a take home potential therapeutic to treat depression and other conditions without the trip.
How do we navigate the regulatory landscape?
First of all, from a FDA perspective,what fixed those combination paths is a very well-defined path. It 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. That’s a well-defined path that we’re following that’s been used with other drugs before.
From a legal perspective, of course, Terran follows all the laws. We use 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. 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.
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, or may not want to trip. The patients may have religious or other reasons why they don’t want to experience a trip. All of these people need access to care. By harnessing those aspects of the psychedelic for those patients, we can improve the access of who will be able to get this treatment at a dramatically lower cost.
Emma Moran: The partnership with Columbia University for an AI-enabled imaging software platform and recent FDA clearance of NM101 is fascinating. How does this technology work and what potential impact do you foresee in neuropsychiatric conditions like Parkinson’s disease?
Sam Clark: We’re extremely excited about the recent FDA clearance for our technology. This is the world’s first FDA clearance for an MRI imaging software to measure a biomarker or MRI scans that are neuromelanin sensitive. This is the 1st neuromelanin sensitive MRI FDA clearance for a software to analyze neuromelanin sensitive MRI scans.
Neuromelanin is a compound that has been studied for about 20 years. Actually, discovery goes back longer, but it’s mainly been the focus studies that have gone 20 years. You’ve got over 500 patients that have been studied. There’s over 50 clinical trials that have been done.
This is a biomarker for dopamine in the brain. All of us 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 neuromelanin. All of these different clinical studies have shown that neuromelanin can provide potentially useful adjunctive information.
When a doctor is evaluating someone for Parkinson’s disease or other neurological conditions, having access to neuromelanin information is potentially very useful. Neuromelanin 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 neuromelanin, and the neuromelanin becomes much higher than normal.
Again, having access to that was shown in clinical studies to be potentially very useful. There were even clinical studies that showed having access to neuromelanin information may help predict which high risk patients go on to develop full schizophrenia. Despite all that, neuromelanin was never FDA-cleared. There was no software that was capable of measuring it.
At Columbia University, scientists, Guillermo Horga and Clifford Cassidy developed initial algorithms that fully automated and enabled that measurement of neuromelanin. We then licensed those algorithms in, built them into a full cloud-based deployable platform submitted to the FDA for clearance. We recently got that clearance. Now, for the first time, doctors will be able to access that information as adjunctive information as they make their evaluations.
Emma Moran: I was just going to say, congratulations.
Sam Clark: Thank you.
Emma Moran: Terran 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? How do you envision the technology being utilized in, say, universities and treatment centers?
Sam Clark: There’s a couple of different things there. We have set up, for example, sponsored research with Columbia University. They’re developing new algorithms, applications, software studies, and clinical trials. We also have a collaboration with the University of Ottawa and McGill University. They’ve used the software in different patient populations, such as Alzheimer’s disease.
We envision these collaborations growing. We’re always happy to collaborate with academic groups. We’ve gotten great [00:10:00] data in Alzheimer’s disease, Schizophrenia, and other conditions that the researchers there have been making great progress in all of these conditions. One of the other things is they’ve developed new ways to harmonize data across different scanners and just improve the software altogether. They’re doing a great job and we’re very excited to collaborate.
Emma Moran: Terran is a leader in the GMP manufacturing of psychedelic compounds and in the drug discovery and design of novel optimized compounds. Can you share insights into the challenges and opportunities that you’ve encountered in the psychedelic development space? Especially with novel salts, polymorphs, Prodrugs, and psychoplastogens?
Sam Clark: Terran is a GMP manufacturer of psychedelics. That’s Good Manufacturing Practices. That’s a set of regulations that govern the manufacturing of compounds used for human use. Terran is, we believe, the largest, or if not one of the largest, manufacturers of psychedelics in the world. We manufacture at scale psilocybin, LSD, MDMA, and other psychedelics. We provide these, free of charge, to licensed researchers and clinics who want to use them in their clinical studies.
It took us actually several years to ramp up this manufacturing to the capacity it’s at now. We’re also using it for our own upcoming clinical trials. It was a challenge to get that all set up. But, we have an excellent manufacturing team at Terran. They do a lot of these big GMP campaigns. We’ve done that for our other drugs, like Idazoxan and the antagonist 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.
That’s one of our exclusive partnerships with Sanofi. I think you touched on the discovery program. Terran also has a big drug discovery program. We’ve created more new psychedelics, we believe, than any group in history. Last year we had approximately 40 medicinal chemists working on new psychedelics.
We created new versions of a compound called DMT. The world’s first orally active form or elective 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, methylone, 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 has less side effects than the other one. We’ve created what we call psychoplastogens which are compounds that natively don’t have any trip. They don’t have to be combined with any antagonists. 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. We have psychedelics that don’t act at that receptor at all.
We’ve pushed forward on a number of other breakthroughs across the pipeline with new antipsychotics. Terran has recently entered the metabolic space. We’re creating Peptides that are new versions of, basically, 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. We’ve been very active there. Terran has a filed approximately 200 patents across the new psychedelic and drug discovery space for new compounds. That combined with our manufacturing makes for a very robust continual pipeline of breakthroughs. We’ll be announcing some of our biggest breakthroughs later this year.
Emma Moran: Looking ahead then, how do you see Terran Biosciences contributing to the renaissance in neuroscience? What role do you anticipate your company playing in shaping the future of therapeutics for patients with neurological and psychiatric diseases?
Sam Clark: I’m very proud of the team’s accomplishments to date. They’ve done so much building out new psychedelics, new psychoplastogens, bringing Idazoxan back into the clinic, and building out fixed dose psychedelics without the trip.
But, there is a lot to do still. We see Terran’s role as pushing forward these new discoveries, and breakthroughs, while improving in areas 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 most thought couldn’t be fixed. We fixed it, and turned it into a nice “once daily.” Like the drug Idazoxan and other compounds.
We know the patient is the most important stakeholder. We prioritize patients above any other priority at Terran. At the end of the day, the fact is that patients are suffering. Where we see Terran [00:15:00] going is that we’re not content to sit on the sidelines, and just hope somebody else develops these treatments. 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.
Emma Moran: Thanks so much for your time and your thoughtful insights today, Sam.
Sam Clark: Thanks for having me on.
