Hello, and welcome to our presentation featuring Cybin, which trades under the ticker CYBN on the New York Stock Exchange American, and the Cboe. My name is Ben Shamsian, Vice President of Lytham Partners. For today's discussion, Doug Drysdale, CEO of Cybin, will be taking us through their slide presentation, followed by a comprehensive Q&A session discussion. With that, Doug, let's get started, and welcome. Hey, thanks, Ben, for having us at the conference. Good to see you again, a nd thanks to everyone that's listening for the opportunity to share a little bit of the Cybin story with you. I mean, first off, let's just say Cybin, as Ben mentioned, is a public mental health-focused biotech company. I'll say that I don't think it's an exaggeration to say that what we're seeing with early results for our Phase II depression program is nothing less than a potential paradigm shift in the way we treat mental health. Today, when we think about standard of care for treating patients with depression, it's been SSRIs, SNRIs for the last 40 years or so. Those treatments, as we know, provide relief to a relatively small number of patients. About 1/3 of patients find themselves in remission, with the remaining 2/3 dealing with some level of symptoms on a daily basis, some blunting of their symptoms, but also blunting of their emotions. These treatments also take a long time to work, 4-6 weeks or so, and come with well-known, well-described side effects such as weight gain, sexual dysfunction, insomnia, and cognitive effects. So what we've been doing for the last 40 years or so, since the discovery of Prozac back in the early 1980s, is trying to treat the signs and symptoms of depression a nd what we're working on at Cybin potentially here is an opportunity to change the course of disease and intervene, and not just address the signs and symptoms, but attack the underlying course of depression. What we're seeing in our Phase II study are very rapid onset of effects, effects that occur within one day after a single dose. We see incremental benefits of a second dose, which we provide three weeks later. After two doses in our Phase II program, we saw 75% of patients in remission from their depression. A t a 12-month follow-up, 71% of patients still in remission at 12 months after just two doses. So this is clearly a paradigm shift in how we think about treating depression. It has a potentially huge impact for patients, but also on the mental health care system overall. Today, if you're a new patient trying to see a mental health professional, psychiatrist, it's pretty difficult. About 18% of psychiatrists are open to seeing new patients. T hat first visit, patients are likely to have to wait 40-70 days, depending on whether they want a virtual visit or an in-person one. These are also high-touch patients. They see their physician six to nine times a year. They're constantly changing doses, changing medications, dealing with side effects. So we have the potential here not only to help patients, but also to intervene. If we can treat patients just twice a year for their depression, two doses with effects that last a year, then we have the potential to pull patients out of the system and free up resources so that psychiatrists can see many more patients. So Cybin has two clinical programs underway, CYB3 and CYB4. CYB3, we're targeting major depressive disorder a nd we've initiated a Phase III program with that asset late last year. This program has been granted Breakthrough Therapy designation by the FDA in February of 2024, and following those Phase II results, our first Phase III study is well underway. For CYB4, we're in a Phase II program for generalized anxiety disorder. That study is recruiting well, and we expect top-line results around the end of quarter one this year. In addition to the clinical programs, we have a wide range of early discovery assets and IP, a very large IP portfolio, and well capitalized to get us through to top-line Phase III data with CYB3. Quickly, the team has had a lot of experience in mental health, working on a number of blockbuster drugs, and has managed 60+ INDs with the FDA. So a very seasoned group moving these assets through the clinic, so this is what our pipeline looks like today. CYB3 is deuterated psilocin. Psilocin is the active agent in psilocybin. Psilocybin is not an active drug. It's a prodrug that requires metabolism to psilocin in the body, and that metabolism is inefficient and inconsistent, i.e., it varies between patients, so taking the active agent and applying deuteration enables us to deliver an oral capsule for the adjunctive treatment of major depressive disorder, with top-line Phase III results coming around mid-2026. CYB4 is deuterated dimethyltryptamine, or DMT. Here, we've used both deuteration and an intramuscular formulation to retard the PK profile, so typically, an inhaled or an intranasal DMT dose might last five or 10 minutes, a very aggressive up-and-down rocket ride, which clinically is quite challenging. By applying deuteration and an intramuscular formulation, we've managed to extend that duration out to about 90 minutes, with patients spending most of their time, these anxiety patients spending most of their time in the tail of the experience where the psychological work is being done. So as I mentioned, that Phase II study in GAD is underway, and we expect top-line results around the end of quarter one of this year. W ith that, Ben, I'd be happy to answer any questions you have about the pipeline, about the results we're seeing so far. All right, great. Thank you for that, Doug. Let's start with you've made a couple of key announcements recently as it pertains to the lead candidate, CYB003. You've announced the initiation of the Phase III program, released 12-month data for the Phase II program. Before we delve into the Phase III program, for context, can you review with us the key takeaways from the 12-month data? Yeah. I mean, this is, I think, we're the first company working on these kinds of molecules that has delivered 12-month data. I think we've seen a number of small studies showing short-term efficacy. So we're not surprised by our short-term efficacy results, where we saw 75% remission rates after just two doses. I think what is remarkable, though, is that when we follow patients up for 12 months, we still see 70+ percent of them in remission 12 months later. I n terms of response, we see a gradual increase in response over time. So it's intriguing that dose one provides maybe a 40%-50% response rate. Dose two increases that to around 70%-75% or more. Th en we see a gradual increase in response rates in some patients over time. S o in that 12-month time set, we saw 100% of patients responding 12 months later, and about 75% or 71% of them still in remission. I remember that remission means no depression. It means a MADRS score of less than 10. T ypically, when we talk about depression studies, we don't really talk about remission because most drugs don't provide that. We talk about response rates, typically. So this really is not only seems to be very effective, but very durable in terms of effects as well. Okay. I mean, certainly, the data is impressive. How would you address those who say that the sample size, the population size was small and may not be representative of sort of the target population at large? Yeah, look, I think that's fair to some extent in that this is a relatively small study. It was 36 patients. We didn't need a large study to tell us that this molecule was going to work. There's been a number of other studies that we could look to for confidence there. But we wanted to show that this novel compound that we've created could deliver efficacy and, of course, safety as well. The other thing I'd say is that not all data is created equal. So if we had had, say, or any study had had a fatal anaphylaxis from just a single patient, you wouldn't dismiss it as being just a single patient. You take it very, very seriously. When we're seeing 100% response rates and essentially 100% remission because the few patients that didn't make it into remission missed a remission cutoff by one point on the MADRS scale, which is not clinically relevant. When you're seeing 100% response and 100% remission, even in a small sample, you can't ignore that. We accept it's a relatively small sample. We don't expect to see 100% response rates in Phase III, of course. What a great place to be starting. From our point of view, from an investor point of view, this is a very strong starting signal as we go into Phase III. Okay. That's helpful. Let's move on to the Phase III program. You've entitled it Paradigm. Can you give us an overview of the design of the program, talk about the enrollment process, how long the screening process will take, and when you anticipate the first dosing to happen, and sort of the targeted readout timelines? Sure. So we spent some time in the summer with FDA working closely on this Phase III design a nd that's part of the benefits of Breakthrough Therapy designation, is it allows us to have this more consultative approach with FDA. I'm not sure everyone realizes, but Breakthrough Therapy means that we're obligated to create and design the most efficient path to approval. FDA is committed to contribute and guide us on that. So it's not just a tick-the-box sign-off from a safety or ethics perspective from FDA. There really is true back and forth on patient populations, endpoint definitions, etc. So that's been very helpful and again, helps to de-risk the Phase III program. The Phase III program consists of two short-term studies with primary endpoints at six weeks, secondary endpoints at 12 weeks. Two 12-week placebo-controlled studies and a long-term extension where we roll over patients from the first two studies into an extension program where we follow patients up for a year after the second dose. We allow those patients who relapse or don't respond in the first studies to get a round of treatment. The goal here is to demonstrate short-term efficacy at six and 12 weeks, and then also at a longer term over a year to look at what the relapse rates might look like and what the redosing schedule might look like. The first of the two studies is a two-arm study. It's called Approach. This is two doses of CYB3 compared to two doses of placebo three weeks apart. About 220 patients in that study, randomized one-to-one. 110 patients per arm. We initiated a study at the end of last year, and screening has already begun, so I imagine that we'll see patients starting to get dosed fairly imminently here. We're targeting about 40 sites across the U.S. and Europe. Most of the sites will be U.S., maybe around 30 in the U.S., and that means all we need is six or seven patients per site, frankly, over the course of the study to deliver that 220, so we've been pretty conservative in our expectations, conservative in our recruiting expectations as well. I think it's best to plan that way, and based on those quite conservative recruiting assumptions, we expect to read out data around mid-2026 from that study. The second study is a three-arm study, and I can come on to this a little bit more. It's designed to address some of the challenges with CNS drugs. All CNS drugs create a level of functional unblinding, and this second study is designed to address some of those challenges. Okay. I want to talk about psychotherapy. What role, if any, will psychotherapy play in these studies? We don't provide any psychotherapy during dosing. Frankly, patients are in that state. They are uninstructable. Psilocin impacts the language centers. It's really impossible to perform any kind of psychotherapy with patients while they're being dosed. In fact, during the dosing sessions, patients are wearing an eye mask, and they're wearing a headset. We're intentionally helping them to cut out all external distractions so that they can focus inwards. The last thing we want to do is disturb them and disturb that psychological process. We want to leave them alone. Pre and post-dosing, of course, we want to make sure the patient is safe. Pre-dosing, there's a certain amount of psychoeducation, informed consent, setting expectations for the patient. You want them educated going into these treatments. We also want the patient going in with some level of intent focused on their condition. The post-dosing follow-up is like you'd have with really any treatment in that we're following up for safety to make sure no ongoing side effects or lingering effects, but also following up for efficacy as well, giving the patient an opportunity to share with their physician what they experienced and how it's impacted their condition, so typical kind of care envelope, if you like, pre and post, but during dosing, there's no psychotherapy being performed. Okay, great. The single most important concern that the FDA had with the conduct of MDMA-assisted therapy development program was the functional unblinding issue. Can you detail the steps that you're taking with regards to Paradigm to satisfy the FDA a nd sort of we won't have the same issue again here when it comes to NDA submission? Yeah. So I mean, first of all, to say that this was a big issue raised at the FDA AdCom by the advisory committee, not necessarily an FDA issue, but something that was focused on by the advisory committee. All CNS drugs demonstrate a level of functional unblinding a nd what that means is if you're taking an SSRI or a benzodiazepine or an antipsychotic, the chances are you know you're taking the active agent in one of these studies. O f course, patients come into studies like this hoping to get better. So what that creates then, if patients can tell that they're taking a drug, is an expectation that the drug will work. So this is a challenge. This is a challenge in all CNS studies. It's not specific to CYB3 or specific to psychedelics. What we've agreed with the FDA to do, and this is part of their guidelines as well, is to, as part of our Phase III program, one of the studies is a three-arm study. A gain, we're looking at two doses, three weeks apart. I n this case, we'll be comparing the active high-level dose that we're testing, 16 milligrams of CYB3. We'll look at a mid-dose of CYB3, so eight milligrams, and then a placebo arm. So there are two active arms and a placebo arm. T he intent here is, one, to show some level of dose ranging. Can we see a differential effect between eight milligrams and 16 milligrams? We certainly expect to see that based upon the PK/PD profiles that we know these doses. But in addition to that, these are psychedelic naive patients. So they typically don't have any kind of reference point for what an experience should be. So whether they're receiving a 16-milligram dose or an eight-milligram dose, they'll feel something, but they wouldn't necessarily be able to tell us or know themselves if they're taking the high dose or the mid-dose. So that means that the expectancy bias kind of cancels itself out, and we can focus on the differential impacts of the active dose versus placebo. In addition to that, we're introducing typical gold standard measures such as all of the raters in the study that rate patients' depression scores are blinded. They're remote. They have no idea which dose the patient received or any of the effects or experiences that the patient had. T hen any of the monitors in the study and those interactions the monitors have with the patients are all recorded a nd we're using real-time manual auditing and AI auditing, real-time screening to make sure that these monitors facilitate to stick to the script and are not biasing the patients in any way. So I think we've taken a lot of steps to address this issue that the FDA is very familiar with. Okay. Doug, you've mentioned that you would like to make an NDA submission on a rolling basis. Help us understand what that means. Does that mean you can start the submission after the sort of Approach study readout in 2026? Help us sort of think about that a little bit more gradually. Yeah, so this is another benefit of Breakthrough Therapy designation, is that we expect to be able to take advantage of all the fast-track tools at FDA, which means accelerated approval, priority review, so part of that will be our plan is to submit data on a rolling basis, so that means different elements, different modules of the NDA will be able to submit to FDA as and when they're ready, so CMC, clinical pharmacology, and then efficacy data from each of the studies as and when they're ready. This is obviously much more efficient as it spreads out the review requirements for FDA, so they're not having to do it all at once at the end. It also means that we can take any learnings or feedback from FDA along the way. We're not, again, not waiting all the way until the end of the process to get any feedback and make any adjustments. So that, I think, is a pretty typical approach with this kind of Breakthrough Therapy status a nd we hope that ultimately, the final review of the entire NDA, we will be able to get in that priority review timeframe of about six months. Okay. Let's talk about the balance sheet here. As of the third quarter, you had about CAD 154 million in cash. That's about $110 million. How far does that take you with respect to the funding of the Phase III program? Yeah. We've been pretty efficient with our capital. We raised $150 million USD in March of last year a nd as you say, there's still a good amount of that remaining. So we've been very cautious with it. We've also maintained headcount at a pretty modest level where it's sort of 50-60 folks compared to our peers that have close to 200. So we've really tried to do this work in a very lean way. So it means that the capital that we raised will get us through to a number of catalysts. First of all, end of this quarter, we expect top-line Phase II data from our generalized anxiety disorder study with CYB4. Very excited about that. It's a quick 90-minute experience, and we expect some rapid results. T hen very exciting, of course, is the first top-line Phase III readout for CYB3 in MDD, which will readout in mid-2026 a nd the capital we have on the balance sheet today takes us through at least those milestones. Okay. T hen just looking at the share price here, you've had a good slew of positive news for some time. Doesn't seem to be reflected in the stock price. What do you think the investment community is missing or sort of is underappreciated here? Yeah. That's always the $100 million question, isn't it? It's intriguing to me and frustrating as well in that I know looking at what we have, we have the best data in MDD in the sector, perhaps the best data in MDD ever. I mean, I don't think we've ever seen these kind of results lasting 12 months after just two doses from any treatment in the past. But even with the best data historically, we had the lowest market cap in the sector as well. So to me, that's an obvious mismatch. It seems to me, as an investor, that would be an opportunity. So I think it's just going to take us some time to get the messaging out there and get the results communicated. I think we're in a bit of an interesting time, though. There are so many distractions right now for investors. First of all, biotech has been a tough market for the last four or five years. It's been tough to raise capital, and returns have been not what people are expecting overall in the sector. T hen there are so many other things going on right now with tech, AI, quantum computing that are generating very large short-term gains, which are obviously really attractive to investors compared to the longer timeframes that it takes with biotech. So we're trying to stay away from those distractions, trying to deal with the distractions that are going on politically: Greenland, the Panama Canal, Canada, tariffs, all of that stuff. Trying to stay away from all that a nd really, our goal is to focus on biotech investors that understand the science, understand the story, understand the potential of what we're trying to do here for patients over the longer term. Not to mention cryptocurrency. Yeah, exactly. It's easy to get distracted by those sort of short-term opportunities. I get it. But hey, we should all be diversified, right? Absolutely. Well, thank you, Doug, and thanks everyone.