I'm Sumant Kulkarni, a senior biotechnology analyst here at Canaccord Genuity, and it's my pleasure to have Cybin here with us today. Cybin is one of the companies that participates in the psychedelic therapeutic space. It's not been short of excitement, and that would be an understatement over the last few days to weeks. Cybin's at a very, very interesting point in time, had good durability data with their CYB003, which is a deuterated psilocybin analog that's in trials right now for major depressive disorder as an adjunct treatment, which is a point of differentiation for the company. They also have CYB004 in a phase II trial for generalized anxiety disorder among all the other things that are going on at the company. So now we wait for more data that's coming in. With that, I think it's a good point to hand it off to Doug Drysdale, the CEO, who's here. I think the first time we met was back in 2012 in a previous life, and you've been there, done that, and a lot of pharma stuff. So, I'll start. Now, just set the stage a bit, what kind of attracted you to Cybin as an opportunity? Oh, it's clearly the opportunity to make such a dramatic impact. You know, anyone that's been involved in drug development for a long time recognizes that science is incremental, and we make small changes, and very often, new treatments that come along are just a little bit better than the ones before. But when you start to look at the data that's coming out from these psychedelic studies, it's not just one or two studies, it's pretty consistent. The effects are large and rapid and sustained, and that's really quite a paradigm shift in psychiatry, where perhaps we can finally change the course of disease with these treatments rather than just treating the signs and symptoms. So when you see a once in a career opportunity like that, it's hard to, it's hard to look in a different direction. Well, well put, I guess. So the company's on the verge of starting its phase III programs. So as you start the programs, could you provide some details on how you went about choosing the 30 clinical sites, and what made those sites stand out to you, and what helps you in those sites to help set you up for success? So the two main criteria for our phase III sites, so 30 sites across the U.S. and Europe. Two main criteria: one, experience in running psychedelic clinical trials, and two, Schedule I license. Those two things add quite a bit of time to ramping up a site, as you can imagine. Either training staff on psychedelic protocols, or psychedelic facilitation, or preparing and planning and submitting for DEA licensing. They all add many, many weeks. So our goal was to make the ramp-up of the study as efficient as possible. So every single one of the sites has psychedelic clinical trial experience, and their DEA license. So quite simple, really. Many other things, too, but those are two important criteria. Yep, that's fairly straightforward. What's the fraction of U.S. versus Europe sites, and how's the fraction of patients gonna play out? It's about 50/50, U.S. and Europe. I suspect we'll end up with a few more sites in the U.S. than Europe, and certainly expect more patients from the U.S. than in Europe. Just, probably faster recruitment. There tends to be... When I look at studies in general in neurology, U.S. is better at recruiting. European sites are often better quality. So it's a good, it's a good mix. So should I go back to a question which I should have asked? I wanted to switch things up a little bit. Lykos had a recent action date, got a complete response letter for their MDMA-assisted therapy. How has all that changed or refined your thought process as you start up a Phase III trial, if at all? I'll say that the outcome of our review after the Lykos AdCom and the Complete Response Letter hasn't led to any changes. However, of course, it triggered a review of everything that we're doing. I think there was a lot of time spent at the icon, maybe a disproportionate amount of time, talking about functional unblinding. I think that's a bit of a... It's a bit misguided to think that the New Drug Application was not, not approved based on functional unblinding. I don't think that's the case. Right. I think it's simply that the NDA was incomplete. And I think that, based on that, and I think it's consensus, that there's no real read-through to other psychedelic programs as a result of that. FDA is very familiar with functional unblinding. Every CNS drug has functional unblinding. If you're in a study and you're taking a benzo, you know you're taking a benzo. An antipsychotic, pretty clear. I saw a study recently that was looking at this issue, and even a study with sertraline, so an SSRI, 100% of the patients knew they were taking the active. So it's just a factor of CNS drugs. So we're putting in a number of measures, and we just met with FDA last week, actually. We had our initial breakthrough therapy meeting with them, a Type B meeting in D.C. So I would say that the communication is very positive, very collaborative. Certainly not the kind of negative spin you've seen in the media around MDMA. And the measures we're putting in place to deal with functional unblinding include a few things, and this is part of the guidance as well, so no real surprises. First, one of the studies will be a three-arm study. It'll contain a high therapeutic dose, a mid subtherapeutic dose, and a placebo. And the aim is that patients won't know whether they received a high dose or a mid dose, the active patients. And so that should mitigate any expectancy between those. In addition, as is standard, we will be using independent, blinded raters, remote raters. They won't have any insight to the dose that the patients receive, nor will they have any insight to the reaction, the side effects, euphoria, or any of those other reported effects. So they'll be completely blinded to that. We'll also be recruiting largely psychedelic-naive patients. That was a point of discussion with FDA. They're concerned about having a population that's too biased. I don't think they're too concerned about somebody that's tried mushrooms in college 20 years ago, but they're really looking to make sure that these aren't experienced patients, so that's fair. We're also using both manual and AI screening, real-time screening using AI of all of the monitor-patient interactions. That's to ensure monitor-facilitated fidelity, essentially making sure they're sticking to the script. Yeah So there's no bias, but also monitoring patient safety. And then, of course, we have long-term safety and efficacy follow-ups a year, ultimately, that will outlast any expectancy bias. Right. So I think this is an issue that's easily addressed, simply by following the guidance. I guess the best way to address functional unblinding is to get a true dose response. Is that the way to think about this, or? Yeah, it's... So, but when patients are receiving the active, and they're psychedelic-naive patients, then it's likely they won't be able to tell whether it's the therapeutic dose or the subtherapeutic dose, and so you, you confound in that expectancy bias. Right. That's one factor among all these other things- Yep -as well. Understood. In terms of prior exposure to psychedelics, do you have a percentage target in mind for how many people will be allowed into your trial? Yeah, so we have had this discussion. It's the goal to minimize the number. It's never gonna be zero. Yep. You know, and the general population isn't zero, so that wouldn't be reflective of the population anyway. I don't think FDA is concerned about microdosing exposure. It's more about regular users that are achieving a psychedelic experience. So I think, you know, the population usage is around 18%-20%, so certainly less than the population usage, and I think that's quite easy to achieve with a few exclusion criteria. Okay. Yeah. So you have, as a company, a very different approach to this because it's, this is CYB003 as an adjunct treatment in MDD. We haven't seen too many others trying an adjunct treatment approach. In fact, most developers go after treatment-resistant depression, not major depressive disorder. What made you choose what you're choosing, and how is that either beneficial or makes things tougher from a logistics standpoint, from a clinical trial running perspective? Actually, I think it makes it easier. So, 70% of patients with depression are taking some kind of antidepressant. So it, it's likely when they come into a study or in clinical practice, they're taking one or two of those. And it's unrealistic, I think, to expect patients to go through kind of the scary process of titrating off- Mm-hmm ... and physicians to go through the risky process of titrating off in order to take one or two doses. It's not a switch from a chronic treatment to a chronic treatment. It's an interventional therapy. So why wait 6 or 8 weeks when you could just start immediately? So it's convenience and a risk factor. In terms of MDD, you know, it's interesting, in real world, payers and providers don't talk about MDD and TRD. They either talk about depression as in mild, moderate, severe- Right ... or first, second, third-line treatments. Okay. It's clear to us that we'll be positioned as third line. So but obviously, SSRIs are cheap, and they're safe, and they're well understood, so those will be used first. Typically, then, there'll be an adjunctive therapy added in, maybe Rexulti or Vraylar or something like that. And then, the choices get pretty, pretty narrow. And so that's where, that's where we expect CYB003 to be positioned, and simply adding it in to current treatment, and hopefully, you know, patients, if they do well, can come off their background medication. What do you think the potential is for a synergistic effect or even maybe a potentiating effect of use of a deuterated psilocin with an SSRI, for example? There may be. There may be a synergistic effect. We're certainly seeing response remission rates that are higher than have been seen in other psilocin studies, I'm sure. In our phase II study, we saw 75% remission rates, sustained through four months after just two doses, which is quite remarkable. In an earlier study that we ran with DMT, regular DMT, looking at patients in two groups, one group with SSRIs and one group not taking SSRIs, there was clearly a benefit in both response and remission. Almost 100% remission- Mm In the SSRI group, so there may well be a synergy. Okay. If there is, that's great. I think the most important thing, of course, is that there's no interaction, there's no safety issues. I think that's the FDA's biggest- Mm ... biggest question. So you have a very interesting 12-month data set that's coming out from your phase II trial. What do you expect to see in that, and what, what do you, I guess, qualify as success in that trial, at the 12-month timeline? Yeah. So the 4-month data that we showed, the 75% remission rates, when we looked at the MADRS scores, depression scores, the reduction at 4 months, in fact, through, you know, 2, 3, 4 months, was all pretty flat. It was pretty consistent. We didn't see any real regression in MADRS scores over that time frame. So I expect we'll see good, robust, you know, response remission rates. 75% at 4 months is pretty remarkable. If we saw... If we see 50% of those patients still in remission at 12 months, that would be better than anything that's been approved to date. So yeah, we're quite excited about the data, which we'll have in the fall. Right. How are you ensuring that patients who are in these open-label extensions are not getting undue levels of therapy or even maybe using psychedelic products? ... It's very difficult to do. Even keeping patients in long-term studies is challenging. So FDA is looking at quite short-term endpoints in our controlled studies. So as we think about phase III, the placebo-controlled studies will be only 12 weeks. The primary endpoint is 6 weeks, then the 12-week. Keeping patients on placebo longer than that is challenging, and maybe unethical. You're gonna have dropouts. In the long-term extension of phase III, where we'll follow patients for a year, we will be tracking, you know, what's happening to their background medication. One element of the long-term extension will be that patients that relapse or those that didn't respond in the short-term studies will get a chance to have a cycle of treatment. So that may mitigate them increasing their background medications if they can get retreated. But of course, we hopefully will see patients coming off of those, some, some of those background medications. What about the situation where someone takes the drug in the trial, the active, then rolls over into an open label, loves the experience, feels nice, all those kinds of good things, and then decides to have a psychedelic experience by themselves? How would you parse out the effect of your product versus the contribution of that experience to the durability? So in the long-term extension, we'll just be tracking if patients are changing their medication. So if somebody comes off an SSRI or they're adding some adjunctive therapy, and it's just, we'll track that data, and we'll do some stratification, you know. If somebody has another psychedelic dose outside of the study that we're aware of, they'd have to be excluded from the data. Right. Okay. I guess the question is, how would you be aware of that? Is it like an honor system or how is it? We follow patients up monthly. There's, you know, there's monthly reviews with them. Yeah, there's an element of honesty that's required. Okay. We're not putting cameras on them, you know? Yep. Got it. What's your latest thought process on what good durability is like for CYB003? Ideal durability. Yeah, I mean, our internal goal has always been six months as a minimum. Mm-hmm. As I mentioned, at 4 months, the data was pretty robust. I don't see any reason why it won't be very similar at 6 months. You know, the reason for that is that beyond 6 months, we believe FDA starts to look at these treatments as acute therapies rather than ongoing treatment of the same depressive episode. That has implications for the label, it has implications for the safety database and many other things. So, 6 months has always been our goal. I wouldn't be surprised if we saw a re-dosing schedule, on average, for CYB003 of 8 or 9 months or so. Some patients maybe last longer, some a little less. Yeah. It also has important pricing implications, so how are you thinking about that, like, six-month durability, annual pricing, all of that? How does all that math work? Yes, we're still thinking about it. You're absolutely right. With a clear annual re-dosing schedule, it's somewhat easier to compare or benchmark your annual cost, annual prices. As you start to get into retreatment cycles, for some patients, it might be more than a year. It gets a little more complex, but. So we're obviously tracking the data, and we have some time to think about pricing. Now that you've had data with the molecule, you've had CYB003 out for some time, what's your latest thought process on how duration of that molecule might help you target the indication successfully? What we've seen with duration for both psilocybin or psilocin deuterated or DMT is that it appears to increase potency. It appears to increase bioavailability. We're seeing effects at lower doses than we had initially modeled and expected. You know, it's difficult to parse out which elements of the phase III protocol are driving efficacy or will drive efficacy. There are a number of different factors. One, an MDD population, so not including those refractory TRD patients. Two, an adjunctive therapy, so perhaps avoiding any rebound effects from titrating off background medication. Three, a two-dose regimen. We see a clear incremental benefit from a second dose, and the idea behind repeating a dose within three weeks is to lock in the benefits and improve the benefits and have sustained durability. With single doses of psilocybin, we've seen effects begin to regress after six weeks or so. So that was important. And then the molecule itself, the being more potent, we have pushed the dose as high as we think we can go. So it may be a combination of those things. It's hard to say exactly which, but our goal has been to maximize the dataset- Got it As we get through phase III. When could we see the phase III data, top line? Assuming we stay on track, and we're on track now, following this FDA meeting, I hope to begin very soon, phase III, certainly, by the end of the summer. We should see top-line phase III data from the first study in first half of 2026. First half of 2026. Okay, got it. At that time, given that some patients would have had a durability response beyond your initial primary endpoint, number of weeks, do you expect to announce any sort of longer-term durability around the time of that top-line data release, or you don't want to confuse things? Probably not. Probably not. We'll also have a second study that's ongoing, at that same time as well, in parallel. I mean, our hope ultimately here, given we have Breakthrough Therapy designation, is to submit a rolling review, a rolling NDA. And that'll include, you know, various clinical submissions like this from both the short-term studies and the long-term studies, as well as all the other background clinical pharmacology, toxicology studies we're having to run as well. Yeah, moving on to CYB004, that you're gonna have phase II data there. How would you qualify success on that trial? What do you expect to see, given this is, again, a deuterated version of molecule, right? So it's the first time we'll see something on it. Yeah, so this is deuterated DMT, an intramuscular formulation. We're seeing now in our phase II program, very rapid onset of effects, 2 or 3 minutes. Mm. So very, very, very quick. The total session times appears to be around 90 minutes, as we expected, with the patients spending the bulk of their time after the peak PK in, you know, in the tail where the psychological work appears to happen. So that tail bit appears to be important. So that seems to me to be something that's very scalable, certainly fits within the esketamine window, where there's plenty of infrastructure to support that. Yes, we're in a phase II study right now, studying patients with generalized anxiety disorder. You know, when I think about GAD, you know, 40% of patients remain on SSRIs after they try them, so it's a pretty low success rate, and not many choices for patients out there. I mean, in general, we've been seeing response remission rates in psychiatry with psychedelics in the kind of 40%-75% range. I think anything in that ballpark is gonna be very, you know, very interesting, and also from a very scalable treatment, of course. Yeah. You brought up trip times in terms of lower, I guess lower is most likely clearly better, right? In terms of the treatment duration. How do you expect all of this to play out, given you could have a potential COMP360 competitor already on the market by the time you can get to the market? Firstly, is that a fair characterization in terms of timeline and- Well, yeah, obviously, COMP360 is pursuing a different indication and getting a small subset of patients, TRD patients. And across our programs, we're targeting MDD and GAD. There's clearly an infrastructure challenge- Mm. you know, or a limitation. It's improved. It's gotten better over time. It's taken four or five years now, but Janssen has managed to encourage the setup of now almost, I think, 4,500 centers across the U.S., so, and growing. So by the time we come to market, the infrastructure is certainly gonna be better than it was a few years ago, and I think that that's obviously important. But ultimately, those... Ultimately, the scripts will end up falling, the majority of them, within a small subset of those centers, as always happens, 80/20 rule. And so we will have the those centers will run into capacity issues. What we're seeing with esketamine right now is that patients, after their initial induction doses, are staying on the treatment, and they're coming back every two weeks. And so, if patients are coming back every two weeks to these centers, and each center has, say, 8 or 10 rooms, treatment rooms, ultimately, those rooms are gonna get full with existing patients, and you can't take on any new ones. So that makes shorter-acting treatments like the ones that we're developing at Cybin very attractive to those centers. They can see more patients. They don't have to come back as frequently. And it just, you know, helps convince them to continue to add other treatment options into their practice. Right. Going back to 004 and in GAD, you just had MindMed in the room last, how would your 004 be differentiated from the LSD molecule? Well, obviously different experience. LSD and psilocybin tend to be more of a longer and mystical experience that is full of peaks and troughs, I would say, a bit over time. We expect our DMT experience to be quite intense. It's rapid and intense. There's no real fighting it. Everyone gets sort of into that breakthrough space until the drug wears off. We think that's good for consistency and variability. And I'm not expecting any safety differential, really. But of course, a 90-minute experience versus a 12-hour one is quite easy to differentiate. All right. That brings me to my last question. We're almost out of time here. Big picture-wise, you know, what's your thought process around neuroplasticgens, which need not necessarily have a hallucinatory effect? Do you think a hallucinatory effect is necessary for a therapeutic impact? So I mean, obviously, these neuroplasticgens, it's an interesting area of research. And we'll see. We'll see what comes from it. So far, there's no data to show efficacy. I would imagine that if we do see efficacy, it's unlikely to be at a scale that we're seeing with these high-dose psychedelics. It's not... The rapid, large, and sustainable effects that we're seeing, I think those are unlikely to be repeated by these neuroplasticgens. They may be effective. Perhaps the effect size is more like SSRIs or other sort of approved treatments for chronic use, and I'm sure there's a place for that. So when we're thinking about those, if the psychedelic experience is helping to provide efficacy, then what does it matter? If patients are getting better, they're getting better quickly and for long periods of time, then a few hours in the clinic every six or eight or nine months doesn't sound too bad. Got it. I, I do think I have one more minute, so I, I can squeeze in another one. From where you sit, given the data you have, given the data you've seen from others in this space, at what point do you think, you know, major biopharmaceutical companies could sit up and take notice of what you're doing? And somewhat ironic, because many of these products were products of labs at major pharma- Mm in the first place, right? So, how do you see all that playing out? There's certainly a lot of interest. I'm saying this as I'm looking at the Lilly building, which is kind of interesting. I think there's certainly a lot of interest. Any mid- to large-sized company that has a presence in CNS or psychiatry is interested. They're all watching, waiting, doing homework, but it's still fairly early stages. We haven't had a single phase three readout yet. Phase two studies have been relatively small. We've had these, you know, regulatory discussions, as with Lykos, that are always gonna throw in, you know, questions. And as in typical big pharma style, they can afford to watch and wait. But when you think about longer term, when these treatments are approved and the potential impact they're going to have on patients' lives, I don't think that big pharma can afford to miss out, and they won't. It's just a matter of time. All right. Great. Thanks a lot, and thank you to everyone for attending. Thank you for tuning into the webcast as well. Great. Thank you.