The new frontiers of DMT therapies
[00:00:00] Matias Serebrinsky: Hello everyone, welcome to Business Trip. A podcast about psychedelic entrepreneurship, psychedelic may seen is transforming mental, physical, and spiritual health and entrepreneurship will be key to expanding access. Here we explore the business models and origin stories of the most interesting companies in psychedelics. I'm Matias Serebrinsky

[00:00:33] And I'll be hosting today's episode. When I started exploring the therapeutic uses of psychedelics, I was familiar with their ability to treat mental health disorders like depression and anxiety and PTSD. Well, there's more and more research suggesting that psychedelics may treat a much wider range of diseases.

[00:00:53] In today's episode, we're going to focus on DMT and its potential to treat diseases like Alzheimer's, stroke and even organ transplant failure. There are two, the empties that are often studied in psychedelic science NN-DMT and 5-MeO-DMT. Today's episode will focus on NN-DMT. But I'll still mention a few differences between the two DMTs. NN-DMT occurs naturally in some plants, which are used to brew Ayahuasca. In this episode, we'll only talk about synthetic versions of NN DMT.

[00:01:26] The other DMT, 5-MeO-DMT is commonly found in the Bufo alvarius toad. On a molecular level 5-MeO-DMT looks just like NN-DMT with a few extra items attached, both DMTs interact with serotonin receptors in the brain. However they produce vastly different effects. I'm sure we'll talk about 5-MeO-DMT in another episode.

[00:01:51] Today, I'll be chatting with a few biotech companies. These companies are quite early and haven't started trials with humans. It could be five to 10 years before they receive FDA approval. Pharmadrug is a company with several divisions. One of which is developing the empty therapies for organ transplants.

[00:02:11] From pharmadrug. We have Paul Van Slyke, the chief scientific officer 

[00:02:15] Paul Van Slyke (PharmaDrug): studying receptors 

[00:02:16] for twenty years . What I mostly focused on was actually the inflammatory response. And so it was subject matter that I was fairly familiar with 

[00:02:25] And 

[00:02:25] Matias Serebrinsky: Daniel Cohen, the chief executive officer 

[00:02:28] Daniel Cohen (PharmaDrug): we've received orphan drug designation for what we applied for kidney transplants, but they ended up expanding it to more than just kidney.

[00:02:36] Matias Serebrinsky: From Psilera Biosciences we have Chris Witowski. Psilera is developing DMT therapies to treat substance use disorders, as well as neurodegenerative disorders like Alzheimer's. 

[00:02:47] Chris Witowski (Psilera): We are looking initially at psychiatric disorders and these are associated with alzheimer's or dementia patients, because you do have a lot of mood swings with these types of patients, but longer term look to observe these patients for changes in cognition, as well as neurogenesis and things like that

[00:03:04] the DMT can do. 

[00:03:06] Matias Serebrinsky: And finally, we have Chris Moreau from Algernon. They have a program focused on DMT therapies for stroke. 

[00:03:13] Chris Moreau (Algeron): We're focusing on a sub psychedelic dose delivered intravenously. We don't want to be sending people on a trip when they've had a stroke.

[00:03:22] Matias Serebrinsky: Last thing, this episode gets technical. We'll be looking at the anti-inflammatory effects of DMT and cover topics like angiogenesis, neurogenesis, and agonist activities in serotonin receptors.

[00:03:37] One of the hardest and best parts of learning about psychedelic therapies is how complex biology and chemistry are. So put on your goggles and white lab coat, because we're going deep into the pharmacological effects of psychedelics.

[00:03:59] So psychedelic medicine, I would say the most popular use cases have been around depression, anxiety, trauma, but that's not what we will cover today. There's very new or novel use cases that your companies are tackling. And so. I'd like for each one of you to talk about the Eureka moment. How did you come up with the specific indications or target areas that your companies are working on?

[00:04:30] On? Why don't we start with Daniel. 

[00:04:33] Daniel Cohen (PharmaDrug): I guess the Eureka moment was really understanding that first of all, we felt that the neuropsychiatric space was already getting a little bit crowded when it comes to psychedelics. And as we started doing our work and reading the literature, we started to realize that a DMT could possibly have different applications in the body.

[00:04:49] And when we realized that there was literature out there showing that there was a potential for kidney transplants, we started getting to work and looking for different ways in which DMT could be used. And. Potential and kidney transplants, we saw that DMT could have antioxidative and anti-inflammatory properties.

[00:05:06] And that's the Eureka moment where we realized that there might be other receptors out there that can respond to DMT in a way that's very different than in the mind. And that's what we've been working on right now. 

[00:05:18] Matias Serebrinsky: Chris, from Psilera, what was the Eureka moment for you and 

[00:05:21] Chris Witowski (Psilera): Jacie? 

[00:05:22] Well, yeah, I mean, DMT is a very special compound.

[00:05:25] The spirit molecule, personal experiences aside, it certainly has a lot of implications. It is one of those unique psychedelics that doesn't have, we'll say the traditional oral bioavailability, where you can just take a capsule with DMT and, and have it get into your system. 

[00:05:41] Matias Serebrinsky: Bioavailability means how much of a drug actively reaches its destination in the body

[00:05:47] unaltered. Factors, such as age, gender stress, metabolism, disorders, food, and even genetic phenotypes can all affect the way a drug is absorbed in the body. Most psychedelics that are ingested orally have enough bioavailability to have the intended effects. DMT happens to not be bioavailable when consumed orally, unless it's smoked.

[00:06:12] This means if you take it orally, you will not feel any effects because your enzymes will break down the compound. So other potential ways to administer DMT are through IV, intramuscular and through the inhalation of the empty smoke. 

[00:06:29] Chris Witowski (Psilera): So both myself and Dr. Jackie Pslam the co-founder and CSO of Psilera, we both have a pretty broad experience in drug formulation, especially in non oral formulations, like transdermal, methodologies, and tranasals,

[00:06:43] even inhalation methods. So DMT is particularly one of these compounds with a lot of therapeutic applications, but I do think there is work to be done in order to better dose DMT in a more reliable fashion. Intravenous formulations, obviously they're effective, but you know, they have some limitations there as well.

[00:07:00] So we're really looking at DMT. Uh, down the road, cognitive disorders, we are in the process of filing an IND for a DMT transdermal patch. And we are looking initially at psychiatric disorders. And these are associated with Alzheimer's or dementia patients, because you do have a lot of mood swings with these types of patients, but longer term look to observe these patients for changes in cognition, as well as neurogenesis and things like that.

[00:07:25] The DMT can do, you know, one of the real Eureka moments I would say is DMT. It's not really, particularly potent at 5HT2A, in terms of its IC 50 value. And when it was blocked with a 5HT2A antagonist, it still showed these neurogenesis properties in mice. So largely this was deduced through the signal one receptor.

[00:07:49] And when that preceptor was antagonized, DMT, no longer had its neurogenesis effect. And this was in a recent publication. So really there's, there's a lot of applications. Sigma one is sort of new and emerging that has a lot of implications for things like Alzheimer's disease. Donepezil is an improved drug for cognition related to Alzheimer's and dementia.

[00:08:08] That has a pretty strong binding affinity to Sigma one. So bony, combined. Things along with its mood, stabilizing effects, its effects on inflammation in the brain. And obviously just being able to cross the blood-brain barrier is very important. It is pretty difficult to develop drugs in order to do this, but this inherent ability for DMT to do that combined with some of these other factors is I guess all goes into the Eureka moment.

[00:08:33] Matias Serebrinsky: Thank you. What about you ,Chris from Algernon? 

[00:08:37] Chris Moreau (Algeron): So I'll be the first to admit that it was partially market-driven. We were a public company. We already have a clinical research programs in play. The psychedelic space was very active November, December, january. I, I asked my CSO. If, if we took a classic pharma development play approach, was there something for us?

[00:08:57] Could we find an area that perhaps other companies weren't looking at? Could we get an intellectual property position? Very tough. It's an known compound. And we also didn't want to be set up with an NCE program where we were starting at day one with the risk of talks and, and taking years to get it into man.

[00:09:16] So I guess what excited my CSO at the time had background in stroke. And he saw the studies at Allston. Olsen had done the in vitro initially showing that these neurons did respond to psychedelics DMT, one of them, but probably what really got him excited was the stroke study done last year in Hungary where an ischemic stroke model DMT really had a significant impact.

[00:09:40] So going back to Olson, Olson exposed, just neurons in the lab in vitro to psychedelics LSD, DMT over a 24 hour exposure and they actually can measure the dendritic spines and the neurons. These are the connectors. So it, it showed a response. There was this neuro-plasticity or other neurogenesis, this growth happening in the neurons.

[00:10:05] He also did a time study as well. In terms of duration, 15 minutes, 30 minutes, 60 minutes. How long do you have to expose the neurons? But the group in Hungary connected this potential new way to help restart, help the brain heal, help it make new connections by doing their stroke model. So they surgically tie off part of the blood flow to one side of the rat's brain.

[00:10:29] Their control group would have had the surgery and would be just giving vehicle. And then the certain a number of rats would have had the insult, the stroke created and then provided with DMT. After 30 days, they looked at the motor function of the rats and were able to detect that the rats that got DMT had almost a full restoration of motor function when compared to the rats who were not provided DMT in the.

[00:10:57] And also the infarct volume, the area of dead cells in the rat's brain. Obviously these animals are sacrificed to do the study was diminished compared to the non DMT group. So that was the shed. This discovery that is helping possibly brain cells regrow and make new connections. This increased density, the complexity of the cell that translated into a depression study for Olsonn.

[00:11:24] Sub psychedelic dose and then the Hungarian group by an art. I confirmed that. In fact, when you have a stroke model, there's evidence, in fact, that DMT had a profound effect. So that, that was the pathway to where, where we are today. And so just to be clear, we're focusing on a sub psychedelic dose delivered intravenously.

[00:11:45] We don't want to be sending people on a trip when they've had a stroke. This is a moment of psychological disturbance. And there have been a couple of stroke drugs that have failed because folks were jumping out of beds and they were causing a trip. And that's really something that we're hoping to avoid.

[00:12:01] It seems that the sub psychedelic dose is potent probably 0.2 0.3 milligrams per kilogram, but we're, we're going to have that information as we carry on with our preclinical work and ultimately our Phase 1. 

[00:12:15] Chris Witowski (Psilera): And Chris, like I said, a follow up on that. So you might be familiar with Dr. Rick Straussman who theorize that DMT is released into the brain right before you're about to die as, as a way to essentially, you know, as a neuroprotectant, you know, stave the brain off.

[00:12:29] So would you say that this is an exogenous form of DMT, or obviously there's a lot of correlates with, with stroke and near death.

[00:12:38] Chris Moreau (Algeron): It's a good question. And thankfully we invited Rick on as a part of our key opinion leader group. And so I've, uh, been able to have sort of direct access to him. My understanding is it hasn't been completely confirmed that it's produced by the brain.

[00:12:52] I still think there's some professional, respectful, professional disagreements as to whether it's, it's actually indogenous. But I think it opens up an entirely new area that you've got this potentially. Uh, what, why would that be? What's the purpose of it? And is it only released on death or is it released when there's an injury, could be a traumatic brain injury or a stroke?

[00:13:14] What's that healing mechanism? I think we're just at the beginning of it. 

[00:13:17] Chris Witowski (Psilera): Yeah. Unfortunately to really be able to determine if DMT is produced in the brain by humans. It's probably not a great outcome for the human on that study. So to be seen. 

[00:13:28] Matias Serebrinsky: Well, one interesting thing to think about DMT is that how's it possible that the same chemical entity has so many different uses or potentially different mechanisms of action?

[00:13:42] Is that something common 

[00:13:44] Chris Witowski (Psilera): i the bodys really, I 

[00:13:45] Paul Van Slyke (PharmaDrug): think that what's known about these compounds at this point. Rather restricted as a function of the controlled substances act back in 1970, and really that stymied a lot of the research and certainly DMT. We mentioned five methoxy DMT. These are obviously best known for their effects on the serotonin receptor in the brain.

[00:14:06] And the psychopharmacology that they drive, but as people have become more open to studying these compounds recently, as the regulatory landscape looks like it's maturing and the interests of researchers, certainly other receptors that the activate outside of the brain are becoming better known critical importance to the biology that they drive.

[00:14:28] And certainly I think that there's an opportunity to take advantage of some of these signaling pathways is as they're critical to a lot of different diseases. 

[00:14:37] Chris Moreau (Algeron): And I would just add to that, that biology is very complex and you can have a drug where the target and mechanism of action is known and the effects are known and had been studied.

[00:14:47] And I use the phrase poly pharma, maybe a bit differently that drugs can have these multiple effects unless they're studied and understood. Sometimes we're just focused on what's known, but there's the unknown and you can repurpose it. Of course, one drug can have many different effects in the body upstream, downstream of different mechanisms.

[00:15:03] So there it's complex and yes, a drug can actually be doing many, many different things in the body. 

[00:15:09] Paul Van Slyke (PharmaDrug): Just to expand on what Chris just mentioned. I like to think of these things. I've studied receptor biology now for approaching 20 years and probably the best analogy that I've come across over the years is to think of these receptors.

[00:15:22] Almost like a radio antenna. They're receptive to many, many different frequencies. And as you contemplate what these drugs do well, they may operate through similar and overlapping receptor pathways. They drive very different sort of signals as they enter in are processed. So you can imagine an agonist to the serotonin receptor two way.

[00:15:43] I tickles the receptor ever so slightly different and drives very different biology and results. 

[00:15:51] Matias Serebrinsky: Paul mentioned that these drugs are agonists to the serotonin receptor two, a let's break that down. Our body has millions of chemical structures called receptors. These receptors receive a modified signals and these signals are typically chemical messengers, which bind to where we accept or uncovered.

[00:16:11] Stem form of response. Well, an agonist is a chemical that binds to a specific receptor and activates the receptor to produce one of those biological responses in contrast and antagonist blocks or inhibits the receptor the same way locks will only accept specifically shaped key. When a drug binds to a corresponding receptor, it activates or inhibits the receptors.

[00:16:36] Biochemical pathway classic psychedelics like LSD, psilocybin, or DMT are agonist to specific serotonin receptors called 5HT2A it is widely accepted. That the altered states of consciousness produced by psychedelics are at least in part due to the interaction with 5HT2A receptors. I'm curious on how you go from identifying agonist activity in a family of receptors on our receptor to hypothesizing that this drug will have a completely different use case or be effective in a completely different disease.

[00:17:16] Chris Moreau (Algeron): It's the creative mind and it's also the resources. So I scientists that read a great deal are creative about what other effects might go on. Then they have access to resources and they do in vitro experiments and they start to prove a hypothesis and then they start to chase it. 

[00:17:35] Paul Van Slyke (PharmaDrug): I would, I would add to that, that there's really been over the years, an incredible tool chest of unique free agents that can be applied to block particular pathways and look to see what's happening.

[00:17:47] For instance, if you block the serotonin receptor 2a and how are you still seeing the impact of DMT, if you thought primarily the DMT operated through genetic approaches that are being leveraged, where you can knock down particular receptor system pathways and look to see what remains. So there's a lot of different ways that scientists can get to what's going on in the, you know, Chris mentioned the poly-pharmacy of what's going on and there really was all of these methodologies were available, but a relative lack of ability to conduct these studies.

[00:18:21] And so now we're sort of, I feel like we're right at the leading edge of, of being able to reduce these things, to practice, uh, both at the research level and then translate clinically. 

[00:18:32] Matias Serebrinsky: One 

[00:18:33] term I want to bring up for Paul is under your Genesis. And I saw that your research was done in angiogenesis. And a lot of what both creatives are talking about is neurogenesis in a way.

[00:18:50] And so I'm curious in if your background in angiogenesis informed that some part of the research that pharmadrug is doing or how you. Uh, relate those two different types of Genesis 

[00:19:04] Paul Van Slyke (PharmaDrug): studying receptors for 20 years. What I mostly focused on was actually the inflammatory response. And so it was subject matter that I was fairly familiar with.

[00:19:14] So I'm changing receptors. But really studying a lot of the same downstream pathways. Part of my research in angiogenesis, actually also one of my recent manuscripts was in a stroke model. So similar to what Chris Moreau doing, studying inflammation in the brain, following stroke, the hypoxia effects in the brain.

[00:19:35] And an ischemic event. And then really if the vascular supply again, can be opened up the profound inflammation that occurs subsequent to that. One of the things that we don't really think too much about is it's intuitive that when you block blood flow to a region of tissue, that that tissue is going to die.

[00:19:54] But what seems somewhat less intuitive is that actually upon restoration of blood, There is this massive inflammatory response, which also causes tissue injury and death. And so finding ways to combat that dysfunctional extent of inflammation, whether it be in stroke or organ transplant, which is also prevalent and is important and remains, remains to be tackled.

[00:20:21] Matias Serebrinsky: Angiogenesis is the development of new blood vessels. Neurogenesis is the development of new brain cells called neurons. David Olson in his lab at UC Davis was the first one to show that psychedelics are capable of robustly growing the dendritic spines, and neurites in neurons. And the team of Spanish scientists show that at least in mice, DMT does indeed promote acute neurogenesis.

[00:20:49] And furthermore, these new neurons can be linked to detectable improvements in the animal's memory and cognition. The way the empty grows neurons is not mediated through the same serotonin receptor activity that produces hallucinations. What all this ultimately means is that it seems possible that the noon, urine simulating effect of the empty could be totally separate from its house, energetic properties.

[00:21:16] One reason why this is exciting is that people who suffer from depression can sometimes have fewer cells in their hypothesis. It has been hypothesized that boosting neurogenesis could directly fight depression in these people. By helping them increase the number of neurons. I went to go back to Chris

[00:21:36] Witowski for one more question around the science, and then we'll move on to a little bit more on the business side of what it means to build and lead a psychedelic medicine company. The Sigma one receptor was mentioned a few times. Can you explain what is the hypothesis for the relationship between Sigma one and Alzheimer's.

[00:22:01] Chris Witowski (Psilera): Yeah. So I don't, you know, there is some relationship between Sigma one and Alzheimer's disease, agonists of Sigma. One do offer neuroprotection. They even show in humans and animals and anti-amnesia effects people associated with a beta amyloid plaques. So those are. Essentially the protein glomerate that creates long-term Alzheimer's disease.

[00:22:23] And so really what happens is once you have sort of these beta amyloid plaques build up in your brain, your body works like crazy in order to try and digest these proteins and get rid of them. However, this creates a really huge immune response. You create a lot of inflammation. So this is really where the anti-inflammatory effects come in handy.

[00:22:41] Again, talking about some of the neurogenesis effects and actually regrowing brain cells after injury. It certainly works with the stroke and what we're seeing there. And we're trying to apply this to something like Alzheimer's disease signal. One is certainly one of those targets that really only has been discovered in the last 20 years.

[00:22:58] The serotonin system has been known for probably 80 years now, even longer for serotonin itself. And going back to polypharmacology we talk about Sigma one in serotonin. These compounds really are very closely related to serotonin and serotonin binds with the 14 different serotonin receptor subtypes in the brain.

[00:23:17] So it's not a single one of the 14 receptors has activity. Therefore the other 13 are irrelevant. And again, really looking across serotonin activity into Sigma one activity. That's something like Prozac. It's the only SSRI that has any signal, one effects and it's by far the most effective SSR. 

[00:23:39] Matias Serebrinsky: I'm going to mention a couple of words and Daniel.

[00:23:42] I'd like for you to expand about, uh, what that is and what's your theory behind the, um, those words are the Holy Trinity 

[00:23:53] It 

[00:23:53] Daniel Cohen (PharmaDrug): was based on our conversations that we had before the interview today, we kind of realized quickly that to be able to have a commercial strategy for psychedelics and biotech you need something, which I had termed the holy Trinity or a time for it, which is that you need a unique indication.

[00:24:09] You need to be going after something that is not being sought after, by other companies. And there are certain indications that I've become a little bit crowded. That's firstly, secondly, you need a unique formulation. It's hard to put a patent on LSD. Or to put a patent on DMT in its current format. So if you want to have a commercial strategy, you're going to have to have a unique formulation or it's going to help to have a unique formulation.

[00:24:31] The third one is you're going to want a delivery mechanism or divert delivery technology. That is, that is patentable. So that's why we came up with this idea in terms of developing our own commercial strategy. We needed three very important things. We needed a unique indication. We needed a unique formulation and we needed a unique delivery mechanism.

[00:24:51] And that's where we came up with this, the holy Trinity of commercial strategy and psychedelic biotech. 

[00:24:57] Matias Serebrinsky: So starting with the first one unique indication, you definitely have a unique indication. You received the orphan drug designation for organ transplants. What did that process look like? 

[00:25:13] Daniel Cohen (PharmaDrug): Well, you just actually apply.

[00:25:15] There's a way to apply for orphan drug designation. And really when they're blessing you with that designation, it doesn't mean that they are saying that, you know, they w they most definitely watch are going to approve you for an open IND, they're just saying they're acknowledging that. Some literature out there that has been done on that drug for this indication, but they're also just kind of saying, yeah, we accept the fact that it is an orphan indication.

[00:25:41] So really that's the limit of the work. And as we all know, we've received orphan drug designation for what we applied for kidney transplants, but they ended up expanding it to more than just kidney. 

[00:25:51] Matias Serebrinsky: So the FDA you applied for kidney transplant and the FDA was like, you're not being ambitious enough. 

[00:25:59] Daniel Cohen (PharmaDrug): It's not about not being ambitious enough.

[00:26:01] It's sometimes people look at it that way and think that it's a positive, but they're just saying no, the data you gave us actually fulfills a broader category. Again, you're you? When you're getting more for drug designation, you've got to justify that it is actually. Orphan drug and they don't want companies saying, Hey, we've determined that this is the indication that we're going after.

[00:26:20] And that there's less than 200,000 people annually that are effected by it. So we want orphan drug designation. They actually go the opposite way. They're like, no, no, no, no. We want to make it as large as possible. And then you have to narrow it down to prove that it is actually orphan. Now what they widened it to is still orphan.

[00:26:38] But that's the way in which the FDA works. They make it as broad as possible. And it's upon the company. That's doing the research to make it more narrow. It's our job to make it more narrow, not theirs. 

[00:26:50] Matias Serebrinsky: Okay. Can you explain why is an orphan drug designation? 

[00:26:55] Daniel Cohen (PharmaDrug): Well, it basically, there are certain sicknesses indications out there that were less than they marked it as 200,000 patients a year.

[00:27:03] Right. And the problem with that is that there are some serious indications that require the attention of pharmaceutical companies to find a treatment for it. And if there aren't enough people that suffer from it, And then companies won't be going after it because there are other sicknesses that have more people suffering from the indication.

[00:27:21] So it doesn't make economic sense. So the FDA just wants to find an economic incentive for companies to go after sicknesses or indications that have less people suffering from it. And so all they do is they protect you. Right. They make it a more streamlined process. They make the, uh, the process cheaper and they give you a longer term protection once you've, if you've made it through clinical trials.

[00:27:43] So it's just, it's really more of an economic structure to give you, give companies incentive, to go after sicknesses that have too small of a number of people suffering. 

[00:27:53] Matias Serebrinsky: Let's move on to how you find these studies. Since Psilera is a private company, chris, it would be interesting to know how do you seek funding and how do you get financial resources to build a company?

[00:28:09] Chris Witowski (Psilera): Yeah. I mean, I would say in one way, we're quite blessed that psychedelics are well sought after, by the investor community broadly. So I would say as well, we didn't really have to do a ton of cold calls and outreach. Quite fortunate that a lot of the investors came to us who were interested, I would say initially, and this was probably back in the late summer or fall of last year that many companies were looking to go public.

[00:28:34] And for us, that wasn't quite necessarily what we wanted to do is, is more put our heads down, focused on the milestones that we need to accomplish in order to see ourselves as a true kind of biotechnology company. And so being a public company, obviously. It's headaches and is a lot more scrutiny and investor relations and PR that you have to do.

[00:28:55] So we just closed a two and a half million dollar oversubscribed seed round had a lot of demands. So we're quite fortunate in the investors we were able to bring in who certainly see it from a longterm perspective. It's biotechnology. It does take years and five, 10 even to, to bring a drug to market and finding those investors who believed in us as scientists and as leaders in the industry to.

[00:29:18] To ultimately do that. And whether it be establishing partnerships, leading our own clinical trials, but we know this is the first step and it's going to take a lot more money to, to run these later stage clinical trials. But so far we've gotten a lot of great feedback and input from investors. So I would say we don't really have a desire to be public anytime soon.

[00:29:36] And yeah, certainly open to investor conversations and, and those willing to participate on the private side. 

[00:29:43] Matias Serebrinsky: Let's listen to the other side of the story. Daniel what's experience of running a public company. 

[00:29:52] Daniel Cohen (PharmaDrug): It's very similar to how cannabis was at first and how the biotech sector often experiences.

[00:29:59] Right? You've got a lot of highs and a lot of lows. There are moments in time where everybody's enamored. That sector or the sub sector that you're in. And it's very easy to raise money as a public company. And there are times where it falls out of favor and it becomes very difficult. And so it's just a question of being able to raise money when there's demand for that sector.

[00:30:18] And that's something you have to live with specifically within biotech, because, you know, as I mentioned before, this is a five to 10 year game to be able to develop a drug or refine it and get it approved and bring it to market. And so it's being able to understand that you need. Raise the money when the market's paying attention and to be able to just continue to work and move things forward when the market doesn't want to pay attention.

[00:30:42] So it's a very manic existence. 

[00:30:45] Matias Serebrinsky: Chris Moreau, Psilera, was mentioning that in order to raise money, they would meet venture investors or angel investors. How is the process of raising money from the standpoint of a public company? 

[00:30:59] Chris Moreau (Algeron): Well, probably every CEO of a public company that doesn't have a revenue stream that their

[00:31:06] their focus is finding and establishing their next. Potential source of capital, depending on just how the market is, you're managing the company, but then you're managing the public part of the company and your share price, which may be through the roof. It may be in the basement, your depending on when you need to access capital, you're working with brokers, high net worth individuals, bankers, who are, they're either interested in your programming and your stock.

[00:31:36] You may have lots of interests, but your stock is just so low. That trying to raise capital would be very dilutive to the other investors. And at the same time, if you don't have capital, then you can't move it forward. So running a pre-revenue public company, especially in this space, and it depends if you're listed on the Canadian exchange, OTC QB in the US are you lucky enough to be

[00:31:59] level to NASDAQ. It's a very, very difficult job, but the whole idea is that you can access the markets because you have liquidity. If you have a private company and you're going out to get investors and investors some are long, some are short, but if an investor decides, you know, I want to move out of this investment, how do they do that?

[00:32:19] If you're private, but if you have a public company and that stock is trading, you have liquidity in your stock. Somebody can step into a financing. They're usually rewarded with warrants so that if the stock increases, they have the right to buy the stock at a lower price later on, these are all elements it's.

[00:32:35] Uh, I often often sat back and wondered what would be less stressful running a private company that had good venture capitalist support or the ups and downs of running a public company and accessing, you know, your, your loved one day and your you're hated the next. And it's, it's something that a public company CEO has to accept.

[00:32:55] And as you keep wanting to execute on your business plan and hitting your milestones. 

[00:33:00] Matias Serebrinsky: Okay, we are getting close to the end of the interview. I have a couple more questions. One that I just remember, Chris Witowski, you started, you mentioned that you are a natural chemist and you started studying Marine sponges through my research of DMT.

[00:33:17] I found certain Marine sponges have DMT derivatives. Talk about full circle. 

[00:33:24] Chris Witowski (Psilera): Yeah, I mean, well, DMT is pretty widely produced by a lot of plants and animals and to find it in the Marine world maybe not all that unsurprising, some halogenated DMT derivatives, even some halogenated LSD derivatives were found in, I believe in Marine sponge.

[00:33:41] So yeah, I was fairly familiar with a few of these compounds. Actually, as someone I knew as a postdoc and graduate school, he had isolated very, very similar brominated indoles to DMT. And one of the ones that we were working on in graduate school was. Uh, derivative from Antarctic tunakits that interacted quite broadly with the serotonin receptors.

[00:34:06] So I think we even did some, some original studies with that back in graduate school, looking at five HT, two, a receptor binding profiles. But yeah, it's, it's certainly full circle in a way that I didn't necessarily think it would go, but here we are. Can 

[00:34:21] Matias Serebrinsky: you. Smoke, uh, Marine sponge? 

[00:34:25] Chris Witowski (Psilera): I wouldn't,

[00:34:30] I don't know. Who's listening to this podcast, but don't do that.

[00:34:36] Matias Serebrinsky: PSA. Okay. I'm personally interested in the ancient uses of DMT. DMT is one of the active components in Ayahuasca. How do you think about the fact that these medicines have been used for millennia by a regional cultures? Is, does that have any impact on how you think and work with the media? 

[00:35:01] Chris Witowski (Psilera): Yeah. I mean, I'll take that one.

[00:35:02] I mean, obviously having a natural products background, it's something that, yeah, the natural sources are obviously the birthplace of it all and you know, not to go too deep into sort of the intellectual property side of things, but you know, we're not, we're not trying to discover or limit the natural use of DMT, whether that be an ayahuasca or inhaling the purified DMT components of it.

[00:35:29] But you know, more than 60% of all pharmaceutical drugs are derived from natural products. So it's always a starting point to something that is treated or used for the treatment of diseases. Certainly that that's something near and dear to myself and Jackie and it's taken a long time for those, those people to uncover

[00:35:49] those ancient medicines. And obviously it has a lot of potential. And obviously we want to do that in a way that is respectful for those native cultures, but also is able to be useful in a clinical setting and reproducible for those who need it. 

[00:36:04] Matias Serebrinsky: What your biggest learning in building a company in the psychedelic medicine space? 

[00:36:10] Chris Moreau (Algeron): I'm just surprised at what I'm learning about, how the psychedelic drugs were risks have been restricted in the.

[00:36:19] 20 or 30 years we have Dr. David Nutt is on our KOL board, he's a, well-known in this space in the UK. He's worked to try to change public policy and perception of psychedelic drugs, but I'm, I'm surprised at the restrictions that, that have been placed on the drugs, which then have caused us problems with research, but I'm all, I'm more surprised at the openness that I'm finding in talking to investors and media about, and there's an energy, there's an energy and an excitement about what could happen, what could come, whether it's psychotherapy and having access to these compounds.

[00:37:01] And as you get older in life, by the time you're in your late fifties, You start to think, well, what else is there and what is that next frontier? And it's something all of us can experience this. The idea that you can, you could probably open up new paradigms of thinking through compounds like psychedelic drugs is for me personally exciting.

[00:37:22] And I think the, the market, and I think individuals we're getting lots of emails from people. Yes. They've had strokes and they'd like to know how soon we're doing clinical trials and can they participate, but we're also getting emails from people saying this is fascinating. Could this really change how I feel about life and how I feel about myself?

[00:37:43] And there's a, there's an energy and an excitement in this space that I, that I wasn't expecting when we started. 

[00:37:50] Daniel Cohen (PharmaDrug): What I'm really learning here is the fast potential of this class of drugs, or whether it's at the psychedelic level or even at the below psychedelic levels where we've seen that. What we're working on is, is DMT has potentially an anti infflammatory antioxidative.

[00:38:04] And also just in terms of, for the neuropsychiatric, eh, potential, not just, not just for PTSD or depression, but there's so many other parts of the mind or the brain that, that these drugs can be impactful. 

[00:38:17] Chris Witowski (Psilera): Having gotten my PhD as a natural products, chemist, and trying to find new drugs from nature for a long time, the pharmaceutical industry just went away from national products because they realized they could synthesize drugs and they were easier to synthesize and they had tighter binding profiles or better stability than natural products.

[00:38:36] They were easier to manufacturer. So this was, you know, back in the early 2010s where I was getting my PhD. So I was like, well, I guess I'm going to go work for a pharma company. And then the cannabis industry took off, which again, another natural product. And now it's it's psychedelics, which is following a lot of the same paths.

[00:38:54] And. And a lot of ways, sort of like in a dream world coming of age and seeing these two industries kind of recatalize themselves and being a part of that is something very special and very unique to me and my co-founder Jackie and other natural products, chemists, and obviously public perception has changed a lot.

[00:39:12] I think cannabis does have a role to play in that and offering people an alternative to uh, pharmaceutical drugs. Ultimately, I believe that psychedelics are going to totally revolutionize the way we treat any mental health disorder. So being a part of that is really fascinating. And really the last thing that I'll say is I'm surprised by my dad because he's a former Chicago cop, former federal agents,

[00:39:37] this is arrested thousands of people for drugs, and he is completely supportive of cannabis as well as psychedelic medicines. And if he can change his mind about it, I, I believe anybody can.

[00:39:52] Matias Serebrinsky: Here's a recap of what we learned today. NN-DMT has potent anti-inflammatory effects. Inflammation is essential mechanism of diseases like Alzheimer's and also affect strokes and organ transplants. NN-DMT promotes neurogenesis and potentially angiogenesis, because it repairs parts of the brain that have been deprived of blood and oxygen during a stroke.

[00:40:18] While, these studies are super early stage the dosing is most likely to be sub hallucinogenic. I walked away feeling like we're just scratching the surface of the many powers of psychedelic medicine. For decades, research was blocked due to the regulatory environment towards these compounds. Today more researchers are getting permission from universities and the FDA to study psychedelics and more investors are also willing to fund these new companies.

[00:40:48] The door is wide open for discovering even more non-obvious therapeutic benefits of psychedelics. This is a Business Trip, a podcast about psychedelic entrepreneurship. If you liked this episode, you can help us by subscribing to the podcast and leaving a review. You can also tweet us or find us on instagram @businesstripfm.

[00:41:11] And if you're building a company in psychedelics hit us up. My email is matias@businesstrip.fm. I'm your host Matias Serebrinsky. Business Trip is created by me and Greg Kubin. Producer and editor is Jonathan Davis. Sound design and engineering came from Zack Frank. Our theme music is by Dorian Love and additional music credits are in the show notes.

[00:41:36] This is Business Trip. Thanks for tripping with us and we'll see you next time.

[00:41:48] can you smoke a Marine's sponge? 

[00:41:55] Chris Witowski (Psilera): I wouldn't

[00:41:59] Matias Serebrinsky: count 

[00:41:59] you 

[00:42:00] Chris Witowski (Psilera): smoke a Marine sponge. Listening to this podcast, 

[00:42:04] Matias Serebrinsky: but don't do that. don't 

[00:42:11] Chris Witowski (Psilera): do that.