Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
Ever heard of a prodrug? You might say it's a different version of a traditional drug, but can make the drug easier to take, more effective, or more long lasting. And then there are the therapeutic effects of psychedelics. How about psychedelics without the hallucinations? Science tells us they can be helpful in treating depression, anxiety, and the traumas of PTSD.
Dr. Moira Gunn:Well, there's plenty to be learned from this interview. Doctor Sam Clark is the CEO of Terran Biosciences. Doctor Clark, welcome to Bio Tech Nation.
Dr. Sam Clark:Thanks for having me on.
Dr. Moira Gunn:Now you told me in the work up to this interview that made me think twice about what we're talking about today and this is just part of what we're talking about today. I have actually avoided doing interviews before about people who say, hey, we're working with psychedelics and I'm like, no no no not for me. No no no. But you said, well, actually a part of our business here is that we now know that psychedelics hit, you know, about 20 different receptors in human cells, but only one causes hallucinations. So you've gone forward.
Dr. Moira Gunn:Terran Biosciences has gone forward and actually created a block to that hallucination receptor so that scientists and drug companies can study the positive effects. Did I did I get that right?
Dr. Sam Clark:Basically, yeah. And that is that there's been a lot of research showing that while psychedelics act on a lot of receptors in the brain, it's been shown in humans that only the serotonin to a receptor is responsible for the psychedelic trip. And that if you block the serotonin 2A by combining the psychedelic with a selective serotonin 2 a blocker, you can remove the hallucinogenic effects from the psychedelic while maintaining potentially the beneficial antidepressant effects. That's what we're working on with the goal of improving patient access by making a take home medication.
Dr. Moira Gunn:Some people will say, okay. There's no fun here. There's no whatever. It's like whatever benefit you were getting outside of the hallucination was coming from these other receptors. And that I think is the important part.
Dr. Moira Gunn:And you're not just making that for yourselves and your own drug discovery, which we'll be talking about. You're shipping this to drug discovery people all over the world, to companies, to to researchers?
Dr. Sam Clark:So we're not to clarify, we're not anti trip, and there might be benefits of the hallucinogenic trip for some people. But the big problem is that having that trip is a long time commitment, and a doctor has to be present. That that leads to both a large time commitment on the part of the patient as well as a large cost of having the doctor there, and that reduces patient access. So to improve access, we need to take home medication. We're supplying psychedelics to researchers and clinics that are doing clinical studies or preclinical research to improve access.
Dr. Sam Clark:So they have, access. We're one of the largest manufacturers of psychedelics worldwide, and we also make GMP. That means fit for human consumption psychedelics, in Europe, where we then ship to clinical trial sites, so that they can use, the psychedelics in their clinical trials.
Dr. Moira Gunn:And these are familiar psychedelics like LSD and psilocybin.
Dr. Sam Clark:Yes. So basically, Terran is manufactured LSD, psilocybin, DMT, 5 methoxy DMT, MDMA, methylone 2 c b, and several other psychedelics as well, Ibogaine and other derivatives. So that, and we have this robust manufacturing program so that researchers and clinics have access to these psychedelics because psychedelics can be very difficult to manufacture. You need special licenses. And due to the potency, this is
Dr. Moira Gunn:this is very accepted. I mean, science accepts this, and there's some generally proven medicinal benefits here.
Dr. Sam Clark:So far, clinical studies have shown, immense benefit from psychedelics. In randomized controlled trials, we've seen psilocybin, and DMT to have antidepressant effects and LSD to have antianxiety defects and MDMA to have effects on PTSD in phase three trials.
Dr. Moira Gunn:Now there are many aspects to your business. I wanna go to one of them and I wanna talk about a term that many people have not heard of but are it's extremely important and and they will know about it in the future. It's called prodrug. What is a prodrug?
Dr. Sam Clark:A prodrug is when you take the original active molecule that may have some pharmacokinetic issues. And what that means is it the molecule has issues getting absorbed into the body. And you attach a little side chain to that molecule that improves the absorption. But once it's absorbed, it falls off. So, basically, it helps shuttle the molecule in, and then the molecule the prodrug is metabolized in the body to form the active ingredient in your body.
Dr. Sam Clark:So, basically, it's a different way of getting the same active ingredient, but you can improve the absorption.
Dr. Moira Gunn:Now if I understand it, instead of actually just consuming the active ingredient and having a whole lot of chemistry around this so that we can make sure the active ingredient gets into my system. I'm taking something that ultimately produces the active ingredient inside my body?
Dr. Sam Clark:Yes. And in many cases, that's because the original molecule cannot be made to be absorbable. I'll give you an example. DMT is a psychedelic, and the only way to make that orally bioavailable without a prodrug is you have to mix it with a second drug that blocks the breakdown called an MAO inhibitor. And that's found in a in a liquid called Ayahuasca where people mix the 2 together.
Dr. Sam Clark:However, that can cause nausea, vomiting, changes in blood pressure due to the second compound, the MAO inhibitor. There is no other way to make DMT orally active, we made it orally active through a prodrug approach. Being able to, make that prodrug, the prodrug itself natively blocks that breakdown. There is no MAO inhibitor required, and thus, we've made the world's 1st orally active DMT and 5 methoxy DMT.
Dr. Moira Gunn:Okay. Now I've gotta get into, it's not the weeds. It's the basis of all biotech businesses. If you have a drug and you are patenting it, do you also have the patent on the prodrug form?
Dr. Sam Clark:No. Those are 2 completely separate patents because they're totally separate drugs.
Dr. Moira Gunn:Well, that's very interesting because of something part of which many of us have read about in the news, and that is that Bristol Myers Squibb has a new drug just about to be approved. We all know it's gonna get approved, CAR XT, and that's coming right up as of this interview. I'll have to eat my microphone if it's wrong. As of this interview, it is going to get approved September 26th. And tell us about that drug.
Dr. Moira Gunn:This is not your drug. This is Bristol Myers Squibb's drug, CAR XT. What does that drug do?
Dr. Sam Clark:So we're very excited about CAR XT. CAR XT is a combination of 2 very old drugs. One drug called trospium chloride invented in 19 sixties and a drug called zanomaline invented in the 19 nineties. It's a combination of the 2. And together, it works as a very powerful antipsychotic, with a new mechanism of action.
Dr. Sam Clark:The first new mechanism, 50 years. The problem with CAR XT is that because there's bioavailability issues with those old molecules that have not been optimized, you have to take it twice a day every day, which can be very difficult potentially for patient populations like schizophrenia.
Dr. Moira Gunn:Now you've just described drugs for which Bristol Myers Squibb has the patents. But those drugs aren't prodrugs. You're working on and by you, I mean, Taryn Biosciences is working on the, prodrug version right now of CAR XT.
Dr. Sam Clark:Right. So we have made prodrugs of those two drugs, enomelene and prodrugs of trospium. And that's the that's a new innovation that we believe enables the improved once daily version and long acting injectable that can be injected once every few months. And that we call TARE XT. It's our new prodrugs of zenomelene and prodrugs of trospium, which we believe will enable a better dosing regimen to drugs like CAR XT.
Dr. Moira Gunn:So that you're working on this is in the public domain. It's in the news. It's all over the Internet. So you can find this. It is known.
Dr. Moira Gunn:Okay. So now we have Bristol Myers Squibb with a a car XT and it thinks it's got a long patent life on that, but you're coming up with a prodrug version. And that prodrug version is gonna take some time to develop. But it's gonna kinda be introduced before those patents are over with. Right?
Dr. Sam Clark:Right. So CAR XT, basically, there's 2 kinds of patents in biotech. There's general formulation patents that protect the specific drug, and then there's composition of matter patents that cover the whole molecule. Because zenomially and trospium are old, there are no composition of matter patents left. So while CAR XT has strong IP around the specific zenomally and tropospium combination, there is no patents that block prodrugs anymore.
Dr. Moira Gunn:For it. Right. Now originally, would they have would the composition of matter patent have blocked the prodrug?
Dr. Sam Clark:If there was still a composition of matter, it would have, but composition of matter patents expire after approximately 20 years. And zenomelene is, 30 more than 30 years old. And trospium is 60 years old.
Dr. Moira Gunn:Okay. So now you're developing this prodrug. How long will it take actually, do you think, for you to get this to the market?
Dr. Sam Clark:So the exciting thing about prodrugs is they can use the accelerated FDA 505b2 pathway. What that means is rather than repeating all of the efficacy trials again, they can, you can use pharmacokinetic bridging to get a prodrug version of another drug approved. And so what we plan to do is use the CAR XT data package to get our prodrugs approved. Now the FDA allows you to do that 5 years after the approval of the first drug, 4 to 5. And so we believe we can do that
Dr. Moira Gunn:All of the composition of matter patents, as you say, they're well over with. Now let's consider the psychedelics. Those are all very old drugs.
Dr. Sam Clark:Yeah. So look with psychedelics, those are all all drugs that have been invented more than 20 years ago. And in that sense, Taren is improving them via prodrug approach, and there are no composition of matter patents left on the original molecules that could block that approach. It's the same with synovial and entropium. Those are old molecules invented 30 to 60 years ago.
Dr. Sam Clark:And so there's nothing that blocks Taren from making prodrugs to improve patient access.
Dr. Moira Gunn:But what's very clear to me is that Taren has really developed a facility in developing these pro drugs. Is that right?
Dr. Sam Clark:Yes. We have a big pipeline and, during the development of Taryn XT, the prodrug improvements on zenomiallyentropium, that was a 2 year program. And we have a whole pipeline built out where we had 3 different chemistry labs working on the program as well as a lab doing animal studies. We had over 200 full time chemists working around the clock to make those prodrugs over the last 2 years. And we created, over, 600 that we actually synthesized, and we designed over 10,000 prodrugs.
Dr. Moira Gunn:Now Terran is also working on drugs for other conditions. Let's talk about that.
Dr. Sam Clark:Yes. So we're also working on a new, antipsychotic booster called Idazoxan XR. Now the story there is that many years ago, Idazoxan, was under development as an immediate release drug for schizophrenia. However, you had to take it, 3 times up to 3 times a day to get effects. And the development was discontinued because it was too hard to maintain that level of patient dosing.
Dr. Sam Clark:So the company manufacturing it, Pierre Fabre, had discontinued manufacturing. Now Idazoxone had been dosed in over 500 patients across different indications, but it was never approved because of the dosing frequency. It was discontinued manufacturing. So Karen went we licensed in the rights to the drug from Pierre Fabre, and we created a once daily form of the drug called Idazoxine XR. We got the green light from the FDA and put it back in a clinical study in over a 100 healthy volunteers where it showed a perfect once daily release profile.
Dr. Sam Clark:Then we hope to take that into a trial in schizophrenia next.
Dr. Moira Gunn:This prodrug approach, it seems like it could work really well.
Dr. Sam Clark:Yes. So prodrugs are a strategy that, even big pharma has used for many years to improve antipsychotics. We've seen this with Abilify, creating, Aristada, long acting prodrug. So what we're doing is we are we've created the pipeline to create improved versions of drugs that could be antidepressants, antipsychotics as prodrugs. And in doing that, we plan to take accelerated regulatory pathways and basically accelerate the path to get patients more affordable medications, and with a better dosing regimen.
Dr. Moira Gunn:Now the structure of Taryn Biosciences is really fascinating to me. It's actually not structured like other biotech companies. Let's talk about that.
Dr. Sam Clark:Right. Taryn is structured, more like a tech company, and that was because I was very inspired is experts to solve specific functional problems, which enables us to move very quickly and, solve problems that people have previously thought to be impossible.
Dr. Moira Gunn:Good old engineering. Yes. I can always come from the engineering side. Let's get this faster. But, I mean, here's here's the thing.
Dr. Moira Gunn:In engineering, we always talk about better, faster, cheaper, you know. And if there's anything that we've talked about in the pharmaceutical area is why does everything cost so much and take so much time? This seems to me to be one of those areas where there can be major breakthroughs
Dr. Sam Clark:Yes.
Dr. Moira Gunn:To accelerate that process.
Dr. Sam Clark:We agree. I think, look, with this unique structure Taren. I think we have accelerated quite a bit, and we've solved problems like creating the world's first long acting Idazoxan, orally active DMT, long acting MDMA, that were previously thought to be impossible. And another one is the world's first new, form of psilocybin to also, improve patient access.
Dr. Moira Gunn:With and without a hallucinatory.
Dr. Sam Clark:Correct.
Dr. Moira Gunn:But you don't sell to individuals. Do you have no stand? You don't have a pop up on
Dr. Sam Clark:the corner
Dr. Moira Gunn:of 5th and Vine or anything?
Dr. Sam Clark:No. This is to, licensed universities, researchers, and and clinics, especially in Europe. We're very excited to improve patient access, and, increase affordability.
Dr. Moira Gunn:Well, doctor Clark, this has been fascinating. I hope you come back and see us again.
Dr. Sam Clark:Thank you. Thanks for having me on.
Dr. Moira Gunn:Doctor Sam Clark is the CEO of Terran Biosciences. More information is available at terranbiosciences.com. That's Terran, terranbiosciences.com.