Addison, good to see you again, and thanks for having me on. What we're doing at Cybin is we're trying to tackle some of the challenges of classical psychedelic drugs. And one of those is the duration of action. Some of these are very long acting. Psilocybin given orally lasts about six hours, LSD eight hours, MDMA, 10 hours. You're pretty much staying overnight. And the challenge with that is that those treatment durations, that is not really practical or scalable. It's hard to see how addiction clinics or depression clinics can fit those treatments within their business models.

So what we're doing at Cybin is working to transform those classical psychedelic drugs, keeping the efficacy, but using medicinal chemistry and drug delivery systems to make them faster acting and shorter acting so that then they can fit within the business models of those clinics. That then they can deliver care to more people around the world and make these treatments more accessible, for depression, addiction and anxiety.

You're right, there was a lot of work done in the fifties and sixties using LSD and psilocybin. And we are fortunate to have the benefit of that bedrock of knowledge. There have been many studies now performed on psilocybin at institutions like NYU, Imperial College in London, Johns Hopkins, that really show some promising efficacy.

One study at Johns Hopkins that was published in November of last year gave two doses of psilocybin to patients with MDD or major depressive disorder, depression. And they found that after four weeks, 71% of those patients had a clinically significant reduction in their depressive symptoms.

And just to put that into context, 71% is a huge response rate. That's about four times the effect size that we'd see with current treatments today. So really, really promising. Now we have to translate that data into larger clinical studies, but we're off to a really good start. It's a great place to start with drug development.

The way that these psychedelics work, like psilocybin, is that yes, they bind to serotonin receptors, but that's not really the whole story. We've seen under fMRI, neuro imaging, that psilocybin can create this period of temporary neuroplasticity in the brain. And what that means is, it means that different parts of the brain start speaking to each other that don't usually do so. The new networks and new connections, excuse me, are formed in the brain.

And that's really very unusual. And this period of temporary neuroplasticity appears to help the patient become more receptive to psychotherapy. More receptive to overcoming their underlying traumas behind their depression or their addiction.

So these treatments are really quite powerful. And in some studies patients have had remission from their symptoms or their depression or their addiction for months at a time from just one or two doses. So really different from the way we treat things today.

Yeah. So this is another challenge with psilocybin in that it's quite inefficient. When you give psilocybin orally, it goes through the GI tract and through the liver. And the liver breaks it down and you lose 50 to 60% of the active drug before it even gets into the bloodstream, so that's really inefficient. And then part of the reason it takes so long to be treated with psilocybin is because it has to go through that metabolism and be converted to psilocin, psilocin is a pro-drug.

So how do we overcome that and we make it more efficient? Well, we're using a psilocybin sublingual film formulation. This is essentially a strip that gets placed under the tongue that's loaded with psilocybin. And there it's in contact with the sublingual membranes above and below. So the direct contact with the membranes means we should be able to deliver the psilocybin directly into the bloodstream, bypassing the liver. So straight into the bloodstream and right to the site of action, into the brain.

And because we are bypassing the liver, we can give less active drugs, less psilocybin, so it's more efficient. We're hoping to see a faster onset and a shorter duration. And we're hoping to see that data around the end of this year. And that's the goal, to create these more scalable, more efficient treatments that can be more accessible to patients.

Yeah, unfortunately the market is enormous, and it means that there are just so many people around the world that are suffering. I think the number is something like 700 million people around the world affected by some form of mental illness or addiction or eating disorder.

If you add together all of the addressable markets that psychedelics have been developed for today, the total addressable market is something like $300 billion annually. So that's really, truly enormous. And the combined market caps of psychedelic companies today are still only about $10 billion. So there's obviously a long way to go here in terms of value creation.

In terms of business strategy, these treatments are different. And so it's not like treating depression with an SSRI where the patient gets a prescription, goes to the pharmacy, goes home and takes a tablet every day. They're kind of on their own. This requires more touchpoints. So patients will be going, in addition to their psychedelics, going through a psychotherapy program. And they also need to be taking their psychedelics in a supervised session in a clinic. So you need both psychotherapy and infrastructure.

In addition to developing molecules, novel molecules, we have created our own psychotherapy program called EMBARK. It's designed to be a six domain best practices program. That means that we're aiming to deliver consistent therapist training and consistent psychotherapy care across the patient population.

And then we've also formed a partnership with Greenbrook TMS, who run 129 depression clinics across the US. And that infrastructure's important as we develop these clinical trials over the next several years, and we are going to need access to clinics, to therapists, to investigators and to patients. It's not just about developing the molecules, we're also trying to deliver the entire care model, including psychotherapy and infrastructure as well.

Yes, we've got several things coming up. So I mentioned psilocybin sublingual film. We hope to see this pharmacokinetic data, the dosing data, excuse me, around the end of this year. And that'll tell us if we've managed to create something that is shorter acting and faster acting.

And then similarly for our other molecules that we're developing for anxiety and for addictions, we are getting close to wrapping up preclinical studies. And the data started to look really interesting. And I hope that either later this year or early next year we'll be able to share some of that data, where we've been able to demonstrate faster onset and shorter duration with completely novel molecules to treat these other conditions. So certainly over the next three to six months, we'll have several catalysts coming up.

Not really. I think there are some parallels in that these substances are all Schedule One in the US. That's about where it ends. Marijuana now in the US is becoming largely recreational, and many states now widely accessible beyond medical marijuana. But even there, the markets are 20 billion, 30 billion dollars for cannabis. The markets for psychedelics are vastly larger.

There has been some success in developing cannabinoids into drugs. We've seen that with GW Pharma that was acquired not too long ago for about $7 billion. So it just shows you the benefits and the value created by developing pharmaceuticals, but developing pharmaceuticals from cannabinoids is quite complicated. They tend to work in an entourage of different cannabinoids. Which means then you've got to figure out which exact cannabinoids are a benefit, and in which proportion and combination. And that adds a lot of complexity to drug development.

With psychedelics, these are single molecules that generate small molecules. They're well understood. So the chemistry of developing these treatments is far less complicated, and I think they have a greater chance of seeing psychedelics as pharmaceuticals in the future.

And I think developing micro-dosing treatments, pharmaceuticals in the future, is much more challenging than developing macro-dose treatments. And that's what we are focused on, the macro-dose treatments.

And the reason for that is when you start giving really small doses and you're getting really small effects, those effects are much harder to measure. That difference between placebo and a micro-dose effect, you need very large sample sizes to be able to detect that. And so we are talking about thousands and thousands of patients. And over a long period of time, because of these treatments, unlike macro psychedelics, the micro-dosing would be more chronically dosed. Whereas with macro psychedelics you're talking about once or twice or three times a year, potentially.

So to run studies for micro-dosing with very large populations for long periods of time I think is risky and very expensive. So that's not something that we're pursuing, we're very much focused on macro-dosing.

Yeah. One of the ways that I first learned about you personally, but also Cybin as a company, was the interview by Ray Blanco, who's our science advisor. And he put Cybin in his portfolio for a little while, until it seemed like it was getting too volatile to judge when to get in and when to get out.

There has been a lot of speculation in the stock. That's also why I bring up the marijuana stocks because with 2018, 2019, there was a lot of speculation and very small companies were going up and down. How does the volatility in the stock price affect your ability to finance the testing and harvest the data that you need to roll out?

Yeah, that's a good question. We've raised $120 million to date to finance our four active drug programs. So we are well capitalized, we've got a strong balance sheet. But you're right, the smaller companies in this space are seeing a lot of volatility and that has a knock-on effect to the entire sector.

But I think we'll see that calm down. We're seeing a handful of companies now move to US exchanges. We're on the NYSE American, few others are on the NASDAQ. And that just leads to a creation of better liquidity for those companies, stronger balance sheets for those companies. And we're already starting to see a small group of companies, like Cybin, pulling away from the pack.

So we are well capitalized for the next several years to run our programs. I think what we will see as well over the next year or two is some of these smaller companies that have started, and I believe it's in the hundreds, just won't make it. There just won't be enough capital to fund them all. I see a potential for consolidation in this space over the next 12 to 24 months potentially.

That's part of the reason I'm interested in talking to you and following along, because the market for depression and addiction, it's so enormous that it just seems to me like a small company like Cybin could grow very quickly and very large. And that's interesting to the investors who are listening to us speak today.

I'd like to continue talking with you because I'm interested in how the data is going to unfold later this year. I will thank you now for setting the table for us, and then I'll have you back on when we have some data to report. How's that sound?