Latest / BioBoss / Sam Clark: Founder and CEO of Terran Biosciences

Transcript

Sam Clark: Founder and CEO of Terran Biosciences · BioBoss

• 0:00
  John Simboli: Today, I'm speaking with Sam Clark, founder and CEO of Terran Biosciences, headquartered in New York.
• 0:07
  John Simboli: Welcome to BioBoss, Sam.
• 0:09
  Sam Clark: Thanks for having me.
• 0:09
  Sam Clark: Excited to be here.
• 0:11
  John Simboli: How did you find yourself in that role as founder and CEO at Terran Biosciences?
• 0:17
  Sam Clark: Well, it really goes back to growing up. There were a number of people in my immediate family and close friends who were struggling with severe mental illnesses, bipolar disorder, as well as neurodegenerative conditions, Alzheimer's disease. So just being affected by that, I really wanted to better understand treatments. How can we help people develop better treatments? So when I went to MIT and I studied neuroscience to better understand the brain, and then I went to Columbia University, where I did my MD and my PhD. But it was during that time for the MD when I realized that the treatments that we have just aren't that great. They leave a lot to be desired, whether through lack of efficacy or side effects, and there's really a lack of new, innovative treatments. You know, if you think about schizophrenia, for example, almost all of the antipsychotics have roughly the same mechanism of action since the 1960s,you know, just slight variance. And you know, we're just seeing this year, the potential for the first approval of something with the new mechanism. But in general, the principle was, for neuroscience, there isn't a lot of new options. So I really wanted to help people by developing kind of new treatments. But then at the same time, I was looking at other biotechs, and I said, you know, there's a risk aversive attitude in a lot of these biotechs, where they go for safer mechanisms. So it's, you know, I want to, I was noticing, I said at the time, you know, Instagram, Snapchat, Facebook, they were all making enormous progress in Silicon Valley. But on the biotech side, I just said, we don't really have that parallel of a fast moving, you know, biotech that's not risk averse, that's able to tackle those impossible challenges. And so I founded Terran with the goal of building a platform company that would take a different approach to development of neuropsychiatric therapeutics.
• 2:08
  John Simboli: As you made that decision to found Terran and to become the CEO, based on your personal experience and your education and your thinking about the industry, did you consider in those early stages, maybe I'll create this, but I won't be the founder. I won't be the CEO. That's sometimes the case. It's an idea, but you find the person you want to carry that forward. Or did you know from the beginning, I should do this?
• 2:32
  Sam Clark: So when I founded the company, I wanted to push the ideas forward. And people actually had discussed that same idea with me, the idea that, you know, when a venture group comes in and gives you funding, they'll put their own team in.
• 2:45
  Sam Clark: You can be the science advisor, or maybe, you know, something where you're not really running the company. And I always wonder, well, why is that the case? And that's the case, they say, well, they want to bring in someone who's more skilled at the business aspects. But the business aspects, actually, I think you can pick up quite quickly. It's really having that strong science background that I think has really enabled us to move forward faster than other companies in the space, because I stay involved in every aspect of the business. And instead, you know, I'm inventor on over 200 patent applications we put through. I'm the invent, only inventor on the world's first new forms of psilocybin, MDMA, long acting and other inventions that we've made at Terran that have been granted now by the patent office. And so in doing that, I think it actually gave me an advantage. But there was definitely some pushback when I was starting to found the company for people saying, well, we don't typically see someone do this. But at the same time, I had been reading a lot of biographies and studying and said, look, in Silicon Valley, the founders take the company forward. So in biotech, we can do that too. And it really has worked out quite well.
• 3:56
  John Simboli: In those early stages, had you considered the possibility of taking your idea to an existing, to a biopharma company, to a pharma company, and having it developed under your guidance, but within that framework?
• 4:09
  Sam Clark: I thought about it for sure, but that leads to a number of downsides. If you just sell off the idea immediately to Big Pharma, then it may get shelved. You know, priorities often change. And the other thing is, the ideas we were developing at Terran were not safe ideas. This wasn't the case of, hey, we have another, you know, oncology drug with the same mechanism that's been approved, slightly better pharmacokinetics. These were assets that we believe had the potential to really revolutionize the treatment of neurological conditions that already had human data, but had been discontinued by big pharma because they couldn't solve certain problems. So it was already a big risk taking them on and a challenge. And so what I did was founded a company where you can, we would build a team of highly trained operators. And then pull on world experts so that we could move forward to solve these problems. So in that sense, it wouldn't have been the best fit to go straight to companies, because the pitch would be, well, Big Pharma failed to develop these, you know, and we're pushing these high risk assets forward. It's not the typical approach. And then to your other point, what about typical VC funding? The problem there is that it's singularly focused. Companies they like to invest in the most are typically single asset focused companies where the company's only doing one thing. Now we've seen a bit of a switch recently with companies like Cerevel and Neumora, and now the rise of more neuro platform companies, and we see ourselves moving in that direction as well. But you know the past, it's largely been single asset focus, and it still mostly is today.
• 5:47
  John Simboli: So those scientific problems that you were fascinated by and wanted to try to address, that you described for me at the very beginning, as you got into it, a few weeks, a few months into it, did you find yourself following that path of things that you wanted to pursue within Terran, or did those evolve? Did you know what you didn't know? Is another way of asking the question.
• 6:10
  Sam Clark: Some of this goes back to what I was studying during my PhD years. During my PhD years, I was studying and publishing on a receptor in the brain called the kappa opioid receptor. Now we have three opioid receptors in the brain, kappa, mu and delta. And mu is what you think about when you think about opiates. They kill pain, things like oxycodone, Vicodin, all those prescription opiates act on the mu opioid receptor. And same with drugs of abuse, like heroin, a mu opioid receptor. But there's another receptor called kappa that's very effective in killing pain as well. The thing that makes it interesting is that big pharma tried to target that receptor because it has no potential animal models for abuse, so they developed selective kappa agonists that would turn on the receptor as the next generation of analgesic drugs to kill pain.
• 7:03
  Sam Clark: The problem is, people who took those became psychotic, experienced terrible hallucinations. So they said, well, this receptor may be linked to psychosis. And then, interestingly, there was a natural plant called salvia divinorum that also was selected for the kappa opioid receptor and also would cause people to experience hallucinations. But one of the unique characteristics about these is that people described in many reports hearing voices, which is unusual because many drugs that induce psychedelic trips don't really contain those components of hearing voices or really fully formed delusions. Now, then it got even more interesting when I dug into the literature and I said, Wait a minute, in schizophrenia, there are a number of drugs that, in the past, were shown to make schizophrenia worse. One of those was called ketamine. At the time it said, Well, you know, ketamine acts on a receptor called the NMDA receptor. But if, when you really dig into it, you saw there's a number of publications where it showed it also acts on the Kappa receptor and would cause patients with schizophrenia to experience worsening of voices, hallucinations. So then I dug even further, and I did this big meta analysis of kappa opioid antagonists. Now, there were no selective ones that were ever tested, but there were more than 40 trials of non selective opioid antagonists through the 60s, 70s and 80s and early 90s in schizophrenia, and some of those reported amazing results with a new mechanism at ending schizophrenic hallucinations and improving even the negative symptoms, the social withdrawal, the cognitive symptoms. And so the meta analysis showed there was a significant effect on the positive symptoms and a help on the negative. But when I went to try to develop this into a drug, initially, this is back in the PhD years, that's when I found out, well, it's actually very hard to get funding for new drugs. Nobody wants to fund the old drugs because they say, well, there's no IP and, you know, there's a lot of things.
• 9:07
  Sam Clark: It doesn't necessarily, it's not just whether drugs effective, it's whether there's patents, it's whether it's fully druggable, it's whether you can manufacture it. And so there's so many other factors at play.
• 9:18
  Sam Clark: It's whether you can get it approved by the FDA and the regulatory side. That's when I came across. So I realized, okay, this is much more challenging, but that's when we came across another drug called idazoxan from big pharma. And this was a drug that Pierre Fabre in France had developed all the way through Phase Three for Parkinson's tremor. Now the thing is, in Parkinson's tremor, it wasn't that effective, but it was very safe. However, at the same time, it was in trials at the National Institute of Mental Health in the United States, in a collaboration for schizophrenia. And it was the first adjunctive treatment tested where you can add it on to existing antipsychotic regimens, and it would double the efficacy. And the thing is, it wasn't until years later that we saw this in depression with the drug Abilify, where you could have an adjunctive treatment that really became a blockbuster and helped a lot of patients. So in that sense, idazoxan had that potential. The problem was it had to be given up to three times a day, every day, and they said, look, it's so short acting that it's not commercially viable to have this three times daily drug. And even then, it was closer to a four times daily drug with a two hour half life. And so all the trials were discontinued. Pierre Fabre had largely exited neuroscience.
• 10:40
  Sam Clark: The drug was shelved, and it was terrible, because at the time, the doctor who ran the trials, who later invested in Terran and is on our science advisory board, said patients and their families were calling begging to be put back on that drug, but there was nothing they could do, because manufacturing had been discontinued. So our science advisory board made me aware of that compound. We then went to France, met with Pierre Fabre, licensed on the rights to that drug, completed all manufacturing, made a once daily form, put it back in the clinic where it's showing a great once daily profile. Got the green light from the FDA, then to move it forward pending the results of pharmacokinetic bridging study into the larger trial with patients with schizophrenia. And it's by bringing back that forgotten asset that had the potential to be very effective that already was very effective in patients with schizophrenia, and by solving that impossible problem that wasn't able to be solved at the time the drug was too short acting. That's where we really hope to make a difference. So to answer your question, at the time, I didn't know about idazoxan, but I knew about these ideas of forgotten drugs like kappa opioid receptor antagonists and things that had great efficacy but had hit snags, and thus were not at the time being funded by traditional venture groups.
• 12:03
  John Simboli: Can you share any thoughts about how you develop the process for knowing when to make a decision versus when to rely on someone on your team to help you make a decision?
• 12:12
  Sam Clark: The structure of Terran, and this is where we get into the uniqueness of the model is very different than most biopharma companies. I've structured it after the tech companies of Silicon Valley, and in that sense, we have a very small team of highly trained operators. So I have a number of ideas that I want to work on the company, and we have a small team of operators that help keep everything organized. But in order to actually execute any of these ideas, we need the world's best minds around the table, and so what we do is we build out individual teams of world experts. Now this leads to a more flat, hierarchical structure in the company. It's not one of those pyramid top down management where I'm fundraising and telling the general plan, and then you have some managers under there, and senior managers and VPs and whatnot, and they trickle down, and then information trickles up. In that sense it's flat. So I'll be on, for example, the manufacturing calls. I'll be present in all the clinical calls, you know, I'll be in the weeds on everything, and I'll be aware immediately when something's not getting done or something, the train's going off the tracks, and we have really good operators that will keep everything organized, but then we have the best minds in the world on individual teams who are able to solve these problems. For example, initially, before we had fully implemented this model, we had people around the table that tried to fix cytosoxan but didn't have the expertise. It wasn't until we found someone who had done this many times before and had potentially more long acting, once daily oral dosing formulations than almost anyone in the industry who came on board had done this many times before. We built a team around them that was able to take this drug forward and finally fix it. So in that sense, the way we have a rule at Terran where everything has to be backed up by evidence. So when nobody's allowed to say, Oh, just trust me on this. And that goes for any aspect; manufacturing, clinical trials, anytime we reach a difficult decision, you know, people have to bring on, bring expertise to the table like, you know, we should take this path based on this feedback from FDA or based on these other trials that have been done in the past, this is the best route. Nobody's allowed to say, Oh, just, trust me, I think we should do this. I have 20 years of experience, so just let me make this decision, but at the same time, you know, I'm not the one who's going to be saying, you know, I'll make, you know, like we always will bring on regulatory help, for example, we'll bring on external expertise to guide into the final decisions that then I'll ultimately have to make. But I won't override the experience.
• 14:53
  Sam Clark: That's where we pull on external experience to make the guide the decisions that I ultimately do.
• 14:59
  John Simboli: Did you find knowing when, in the end, you had to make a decision, did that feel like a natural progression, or is that something to be learned as a new CEO?
• 15:06
  Sam Clark: So ultimately, I have to make all the final decisions.
• 15:10
  Sam Clark: It's something that you definitely get better at over time, and then you pick up, and the best thing is having many advisors around the table. I mean, if you think about it, throughout history, any time you have someone who has to lead a group of people, the best thing is having that group of advisors advising you. And so I try to bring on as much external expertise. And the most important thing is knowing when you don't know something, and when you realize that you don't know something, we move very fast at Terran to find someone who knows the answer. So there'll be, we can identify, oh, you know, we have this problem. We realize when the current team members also don't have the solution, and we go as fast as we can through our entire network to find someone who has the solution to that problem. And we've been very successful using that fast moving model. And once we have that, then we can make the decisions.
• 16:04
  John Simboli: If someone your team were to be asked the question, well, what's Sam's management approach? That might or might not be how you would describe it, but can you estimate how others would say, oh, yeah, this is how he goes about dealing with the team.
• 16:18
  Sam Clark: Well, I like to stay very highly involved with the team, so we'll be chatting every day is spent with the core team of operators every morning. So we're in constant communication, both in decision making as well as, you know, planning. And I generally have a lot of ideas that I want to do each day. So I'll help, you know, make sure the team's on schedule to achieve those. And sometimes give out new goals, new plans, or readjust quickly if I think the priorities change. So it's a lot of top down information, but the team handles it very well and course corrects. And we'll course correct and change sometimes, many times a week, I'll be making decisions to pivot quickly, and I have a team of operators that'll immediately implement those changes. So there's not a management style where I'll say, Hey, this is what we need to do. Go do it, check in with me in two days.
• 17:08
  Sam Clark: Then we'll do another thing.
• 17:11
  Sam Clark: It's daily feedback and daily course correction. But I want to draw a distinction. It's not micromanagement, where people have to babysit each individual decision, like task. I trust the team to be able to achieve those tasks, to, you know, to accomplish those goals and tasks, I give them. It's just that we move so quickly that the tasks may change rapidly, and there may be new tasks and alterations to those tasks. So I don't have to babysit their execution of the task, but I do have to be very much alert to move and change very quickly.
• 17:51
  Sam Clark: And that's, I think, how we've had our greatest successes.
• 17:54
  John Simboli: Can you recall as a young child, eight, nine, ten, whatever is a formative time for you. Do you remember what it was that you set your sights on? Who knows where these things come from, generally from parents, I'm sure. But do you remember what path you saw in your life and does have anything to do with what you're doing now?
• 18:11
  Sam Clark: You know, it's a combination of things. There was a time when I was around age 10 when I wanted to be a doctor and I wanted to learn about the body, but at the same time, it was really mainly around exploration. I was always exploring things, reading things, you know, trying to understand new things. And, you know, this was during the time in the all this new technology coming out, you know, the internet was just really starting to take off. And computers, and, you know, the first laptops were, you know, just being, you know, developed.
• 18:37
  Sam Clark: This is before smartphones, so and then the idea, also, besides that too, is I would go out.
• 18:44
  Sam Clark: This was during also a time when you would, you would just go get on your bike and go out, hang out your friends, and you'd bike neighborhoods. You'd bike through the woods, you'd bike through parks. You would just go and nobody was checking up on you. You know, you come home for dinner. And the thing is, it there was, it's not a kind of a helicopter mentality we have now. So you're out there exploring and seeing things and thinking things and reading books and and really just dreaming. And that was the idea I wanted to explore. And so I think that's what we're doing now in Terran, we're exploring the brain. We're developing new psychedelics. It's the final frontier of neuroscience. So we're really, I think that's a natural progression of those times.
• 19:24
  John Simboli: When you go for that nutshell, 30 second very brief kind of who is Terran Biosciences, how do you like to answer that?
• 19:32
  Sam Clark: Terran is a platform company, so we do a number of things, for example, in the psychedelic space, one of the largest manufacturers of GMP, I mean, for human use psychedelics. We've created more new psychedelics, we believe than any other group so far with new modifications to the trip.
• 19:50
  Sam Clark: We create psychedelics without the trip. We also create traditional neuro assets like idazoxan for schizophrenia and other antipsychotics. And we have software, AI enabled software, as a medical device to aid in the provided juncture information aid in the diagnosis of neurological and psychiatric conditions. And so in that sense, you know, Terran is a platform company with a suite of options to help people with neuro and psychiatric conditions.
• 20:21
  John Simboli: I imagine it's it often happens that you're at an investor conference, or in some other kind of format, where someone you give that brief description, and you're about to go on, and then you're realizing people may have substituted a preconception for what it is that you're doing. It just happens that's kind of part of the game. So my question is, in this early stage are, is there any kind of pattern that you see where you think, oh, people seem to think it's this, but I have to help them understand it's that.
• 20:49
  Sam Clark: Sometimes, and that's usually when people will get fixated on one aspect of what Terran does. So they'll say, ah, Terran is psychedelics, or Terran is just software as a medical device, you know, or it's just antipsychotics, and they're missing the big picture.
• 21:03
  Sam Clark: Or, even more recently, because we had some high profile patents publish with the goal of those patents actually being that we can bring cheap, affordable, 505 b2 medications to the market.
• 21:15
  Sam Clark: You get the traditional kind of summaries in forums or press saying, okay, is Terran just trying to snap up IP in the space for no reason? Or they can't possibly develop this many drugs, what's the purpose?
• 21:30
  Sam Clark: Missing the picture of using those in order to bring cheap, affordable medications via the FDAs accelerated 505 b2 path and so sometimes people don't take the time to really dig in and see the full picture, but, you know, we're very excited to always tell them about it and move this forward.
• 21:50
  John Simboli: It's been my experience that when people do get that clarification, often the next question is, well, how can a relatively new company that is building itself take on something of this importer of this scale, and how do you help them understand that?
• 22:05
  Sam Clark: Well we've been able to cut costs enormously. We run very lean with that small team of operators that cuts out a ton of personnel costs that would be typical for biopharma. And then we use the consultant model, where we have those world experts come on and help solve those problems, but those are, you know, around specific problems. So it's not you're not carrying, you know, constant, you know, payments when projects are completed. And so we're able to really run very lean.
• 22:35
  John Simboli: Is there something you could share with our audience about mechanisms of action that will help people to understand what you're going after?
• 22:42
  Sam Clark: So let's talk about two of our lead therapeutic assets. So one I talked about before idazoxan, that drug that is adjunctive in schizophrenia.
• 22:50
  Sam Clark: That was one of the world's first selective alpha two antagonists. Now that's a receptor in the brain that helps modulate dopamine release. Now, antipsychotics block certain dopamine receptors on the downstream neurons. That means the postsynaptic side after a neuronal synapse happens that postsynaptic side downstream signaling. But the upstream side is not modulated. Idazoxan modulates dopamine from a higher level up, one level up from what typical antipsychotics do and atypicals do, and by adding that dual control, you're able to provide additional potential for efficacy. And it showed amazing efficacy in phase two trials already. Then on this psychedelic side, what we do there? Well, one, we just make traditional psychedelics with improvements, the world's first orally active DMT, long acting MDMA, things like that. But one of the leads is a psychedelic where we've removed the trip.
• 23:58
  Sam Clark: Now, the way that works is that scientists looked at psychedelics that had shown efficacy, LSD, psilocybin, DMT, and they said, Look, these act on a lot of receptors in the brain. But we also know that only one of the more than 20 targets they hit is responsible for the trip, the hallucinations. That's the serotonin 2a receptor. So these scientists said, what would happen if we combine the psychedelic with a selective serotonin receptor blocker? And they did that, and they found that in animal models, it was able to remove the behavioral effects of the trip but maintain the therapeutic efficacy. So then we move that into a human study where we showed that psychedelic without the trip still maintain all of the functional changes on the brain measured with functional MRI.
• 25:03
  Sam Clark: And so we had partnered with Sanofi, where we exclusively licensed their large neural programs, Eplivanserin and Volinanserin. These are two of the most selective serotonin 2a receptor antagonists known. They had already been tested in 15,000 patients over 100 clinical trials, we got the exclusive worldwide rights to develop those compounds. We're combining them with our psychedelics now and pushing those forward towards the clinic, where we hope to develop a take home psychedelic without the trip, where you can get the antidepressant or anti anxiety benefits without having to experience a trip. We're not anti tripitarian. It can absolutely benefit certain people, but we believe that without the trip, you have the potential to benefit all those extra people who can't afford the trip, or can't take the time for it, or scared by it, or don't want it, and really improve the market at lower costs so that we can democratize access for as many people as possible.
• 26:03
  John Simboli: Do you want to also talk with me about the software side of your development?
• 26:07
  Sam Clark: This goes back to a biomarker called neuromelanin.
• 26:12
  Sam Clark: Now, all of our brains have dopamine, and dopamine gets metabolized a little bit, breaks down every day and it binds to iron in the brain. Now, when it does that, it forms a metabolic product called neuromelanin. Now all of our brains just build up neuromelanin across our lifespan, but in certain neurological conditions like Parkinson's, we lose our neuromelanin, and in other conditions like schizophrenia, we gain additional neuromelanin.
• 26:38
  Sam Clark: Now for more than 20 years, scientists have studied neuromelanin and they've shown that it's a great in the literature, it's been published as a great potential diagnostic biomarker for Parkinson's prognostic ability to predict early detection, and also, and also for schizophrenia and depression and Alzheimer's disease, almost a Swiss Army knife of biomarkers. The problem was it was never FDA cleared, because there was no way to fully automate the measurement and standardize between scanners. Each scanner would measure a little differently.
• 27:16
  Sam Clark: This is on a standard MRI, by the way. So a team at Columbia University got together. They developed algorithms, academic algorithms, in academic piece of software called MATLAB that was able to do that. Then we licensed those algorithms from Columbia, reprogrammed them into a cloud based system that could integrate with any hospital worldwide and passed all the cybersecurity testing and then took it to the FDA, and historically, got this cleared as the first medical device, and currently the only that is labeled for the measurement of neuromelanin MRI analysis, and that now brings that biomarker that doctors have called to be included In the standard of care for many years. This brings it to the clinic for the first time, and also shows that we were able to take an academic convention that typically would just stay in the realm of academia, and bring it all the way to the FDA, reprogram it to FDA standards and get it FDA cleared. And so it really ties into Terran's mission of collaborating with academics. It shows we have a track record of success, and it shows we were able to overcome that near impossible problem, which is 20 years of recommendations and no FDA clearance until Terran was able to do it for the first time.
• 28:36
  John Simboli: Can just tell me a little bit about the benefit for patients of it?
• 28:39
  Sam Clark: Neuromelanin, in the literature has been published as having a number of potential benefits. So right now, our FDA clearance allows this software to be used to provide adjunctive information that, when interpreted by a trained neuroradiologist, could be useful in determining diagnosis.
• 28:59
  Sam Clark: Now, if we go into literature, what is the recommendations from different studies show, and what they're really comparing it to is a technology called the DaTscan. Now this is separate from our label. We're just talking about the literature right now. But what's happened is that in the diagnosis of Parkinson's disease, patients, some of the time they'll so they'll come in, they have symptoms, and they'll go, they nearly 100% of the time they will receive an MRI, and that's not to diagnose Parkinson's, it's to rule out other conditions, brain tumors, stroke, other things. Then a percentage of the time they'll go get a what's called a DaTscan, which involves an infusion of radioactive radio tracer, high dose iodine, takes many hours, can take up to five hours, and can have side effects, and it involves an IV so that can involve pain, and it does expose to radiation. Now, neuromelanin imaging in the literature has been used in clinical studies, and the conclusion of some of those clinical studies was that it was just as effective at providing that diagnosis for Parkinson's as SPECT imaging DaTscan, and it was able to be done in just five minutes on a standard MRI that patient already receives with no contrast. Means no IV infusion, no radiation, just five extra minutes. Now, what we are doing is we are giving doctors access to neuromelanin imaging where they can use it how they want to get that adjunctive information, and use that to help in the aid in their various evaluations.
• 30:38
  Sam Clark: And we believe, based on recommendations in literature that this could really be a big benefit to patients. There's also other studies done by our collaborators, Dr Guillermo Horga, who showed that it could help predict treatment resistance in schizophrenia, Kenneth Wengler, who developed new algorithms to harmonize data sets, and Clifford Cassidy, who showed that it could help predict, this is neuromelanin I'm talking about, and neuromelanin imaging could help predict who will develop neuropsychiatric symptoms from Alzheimer's disease, which could then lead to better patients treatment, as well as help predict post traumatic stress disorder and other neuropsychiatric conditions, substance use disorder and other conditions as well. And so those studies from our collaborators, which use the same algorithms used in NM 101, that's the academic version, have really pushed forward the field, and showing how neuromelanin imaging could benefit patients.
• 31:37
  John Simboli: Is there a way to talk about how the pipeline as a whole expresses your vision for what you're looking to do?
• 31:44
  Sam Clark: It's really about, it's the diversity of the pipeline, about building those, solving those impossible problems. So we've got idazoxan for schizophrenia, we've got the psychedelic without the trip.
• 31:54
  Sam Clark: But it's also about bringing cost effective medications that are affordable for patients, that are not overpriced, and tackling industries where the patient may be priced out of having access, that's something that's very important to me ever since seeing my family members affected by mental illness and friends and the struggle to get medications that may be on brand and difficult or without insurance. And we are pushing that forward very quickly in psychedelics. So there's two sides of psychedelics. One is that new drug that we're developing that doesn't have the trip and but another thing we're hitting very hard right now is we're pushing forward psychedelics towards the 505 b2 pathway, and I want to explain how we've set up the company for success here. Many companies are developing psychedelics for various indications, so we've got companies developing psilocybin, LSD, MDMA, DMT, five-methoxy DMT, methalone, and many others. And those are all compounds in the psychedelic space. Now, those are all old compounds. Psilocybin has benefited humanity for 1000s of years. LSD has been around a good 60 plus years. And you know, MDMA was invented in 1912 and so the idea is that, you know, these are compounds that we had heard initially, some of these companies say, Look, we're going to lock them down in patents around the we can't lock them down in patents on the composition of matter that biopharma typically get because it's expired. The compounds are old. So what do we do? They said, Well, what we'll do is we will, we realize that there's a little bit of a second level here, and that is that the FDA is very strict in EMA about regulating the salt form that your your compound is. So develop a drug, it has to be usually in some sort of salt or crystal called a salt, and then a crystal is the polymorph. And why is that important? Well, it's important because if you have the wrong polymorph, some of them are not soluble. They don't dissolve. And we saw that with an HIV drug previously, where it switched to the wrong polymorph. They didn't realize it, and suddenly the pills weren't dissolving in the patient's stomachs anymore. So the FDA said, Okay, we got to regulate this very strictly. You have to control your polymorph.
• 34:32
  Sam Clark: Well, these other companies have realized, well, if we own the patents on all of the polymorphs, we can control the compound for example, psilocybin was only thought to form three polymorphs period. So, you know, people are saying, well, if one company controls three polymorphs, they'll be able to have a monopoly on psilocybin.
• 34:52
  Sam Clark: And thus, for 20 years, there won't be any generics, because any generic would have to use one of the only three polymorphs available. So we said, we're gonna we're gonna solve this because we're gonna need to bring 505 b2 and I just want to explain for your listeners, the 505 b2 path means that five years after someone gets the drug approved, that's not on patent, the FDA allows you to take all that phase three data, and as long as you show you have a bioequivalent drug that could be as little as a tiny phase one bridging study, you get to use all that phase three data put your drug on the market, and now patients have access to essentially a generic, cheaper drug. So we said we are not going to allow psychedelics to be locked up in 20 year exclusivity. You know, long and we're not what we're talking about, all these old psychedelics. You can't lock them up in 20 year exclusivities, where patients don't get access. People have a brand new, special psychedelic they invented. Sure, that's a different story, but we're talking about good old classic psychedelics, LSD, whatnot. So Terran went out there first, and we completed more salt and polymorph screens than any group in history for psychedelics. And now Terran has been granted the world's first new forms of psilocybin, psilocybin hydrochloride, psilocybin edisylate. This is granted to Terran now by the patent office as the world's first new form, and that's one of my inventions and for new form and polymorph, and that enables us to get around any blocking IP on those old polymorphs, because ours are totally different. And that means if someone goes forward and develops an old polymorph and gets a 20 year patent on it and gets it FDA cleared, the FDA allows 505 b2s all the time with different salts and polymorphs.
• 36:45
  Sam Clark: You just have to show bioequivalency. Terran will be right there at the five year mark with our psilocybin. And we already have full GMP manufacturing. We're manufacturing at scale already, so we're ready to go for that.
• 36:58
  Sam Clark: We're already providing the clinical trials in Europe and non clinical we created the first new forms of LSD. We created new forms of derivatives of DMT. We created new forms of the first new form of MDMA. Was just recently granted, MDMA hemifumaratete, to Terran Biosciences, and so by doing that, we're going to guarantee that patients will have access to these cost effective medications, and they won't be priced out of the market. We're taking risks at Terran, where we are not afraid of risk, and so we took big bets and risks to develop assets and other that were highly effective for diseases that other companies said that it's too difficult.
• 37:38
  Sam Clark: We're not going to touch it. We jumped in there and we got it done. You know, neuromelanin, 20 years nobody was able to get approved. We got it approved, you know, now that's going to the market where it can benefit patients and finally, give doctors access, you know, psychedelics, you know, people.
• 37:54
  Sam Clark: That's been a contentious area, where people are trying to really, you know, carve out companies and develop drugs that could be priced way out of the market, enormous therapy costs.
• 38:03
  Sam Clark: And Terran will be right there with the multiple 505 b2s, where we can give affordable meds to patients and not taking another risk and jumping in there. We're not afraid of that, of that controversy, when it's about helping patients. People are suffering right now from mental and neurological conditions, and we're going to move we're going to move as fast as we can to help them.
• 38:25
  John Simboli: Sam, thanks for speaking with me today.
• 38:27
  Sam Clark: Thank you.