Cybin Inc. (HELP) Earnings Call Transcript & Summary

Hello, everybody. This is Robert Sassoon, Senior Analyst at Water Tower Research. And I have the double pleasure of hosting Cybin's CEO, Doug Drysdale; and the company's Chief Medical Officer, Amir Inamdar, for this fireside chat. So just to remind everybody, Cybin is a late-stage breakthrough neuropsychiatry company committed to revolutionizing mental health care by developing novel next-generation treatment options to address the large unmet need for people who suffer from mental health conditions. Cybin trades on the NYSE American and Cboe Canada Exchange under the ticker CYBM. The company's safe harbor statements can be found in its company filings, which are filed with the SEC and Canada SEDAR. So welcome, Doug and Amir, and thanks for joining us for this fireside chat.

Good to be here.

Thank you.

So Cybin has made a couple of key announcements recently as it pertains to your lead candidate, CYB003, deuterated version of psilocybin. It's an adjunctive to background meds for the treatment of major depressive disorder, which unfortunately affects more than 300 million people worldwide and over 20 million people in the United States. Now you've announced the initiation of the Phase III program and released the 12-month data from the Phase II program. So before we delve into the Phase III program, for context, can you review with us the key takes for the 12-month data? Let's start with you, Doug. And then Amir, feel free to add anything else to that.

Thanks, Robert. Look, I think this 12-month data that we've recently shared answers what I would think -- what I think is the last remaining question about commercial viability. There have been plenty of small studies that have indicated that psychedelics have efficacy, at least a short-term efficacy. And in our Phase II program, we showed that with our psilocin, deuterated psilocin protocol, we were able to make sure that most patients benefited from that efficacy. We saw 75% of patients in remission after just 2 doses. But now what we'll be seeing with this 12-month data is really quite remarkable, and that we saw after 12 months, so 12 months after just 2 doses of CYB003, 100% of patients still responsive to treatment and essentially 100% of patients in remission. We had 2 patients that missed the remission cutoff score by 1 point, which is not clinically relevant. So what -- small numbers, but what we generally -- I think this says to me is that in the real world, when we come to commercialize CYB003, it has the potential to help the vast majority of patients and likely most of them for quite a long time. So that means very infrequent dosing of CYB003. Maybe it's a couple of times a year for most patients, which, of course, is great for providers, great for payers, it is great for patients as well. So I think that last question around durability of durability of CYB003 has now been answered.

Great.

Yes. No, that's exactly. And if I may add, I think what we are seeing is not normal, right? We don't normally see these kind of data. And this is an internal joke as well. I shared with the team that guys, especially with the new people who are young into the company, their may be first job in the pharmaceutical industry, and we say, "Guys, getting a breakthrough therapy. This is not normal." We, at least I have waited 25 years in my career to work on a molecule that is a breakthrough molecule, in the same way, these results are not normal. And all of these results have been delivered in the context of an extremely favorable safety profile. I mean we don't talk enough about the safety profile. People take antidepressants for decades. They take them every day. And antidepressants are not benign drugs. They cause a host of gastrointestinal side effects, sexual dysfunction, and things like weight gain. So people are depressed, and they gain weight and it makes them more depressed. So they are not without their problem. So CYB003 coming in with a favorable safety profile, we saw no adverse events in the long-term follow-up up to a year. We saw no long-term sequelae of this treatment. We did not see any suicidality. Suicidality has been brought up a few times with this class of drugs, and we used a validated measure, the Columbia-Suicide Severity Scale, and we saw absolutely no cases of suicidality. And one other thing we haven't really discussed in the past in too much detail and despite small numbers, you've got data on about 4 participants only, it does seem that even though 1 dose is effective, 2 doses are better than 1. And this is a conscious decision that we took at the start of our program that we will administer 2 doses, 3 weeks apart. And based on the limited data, it appears that our decision to go with 2 doses was the right one.

Right. Thank you for that. So to the best of my knowledge, nothing actually comes close to the 70% plus, 70% plus remission rates that you actually recorded on the 2, 16-milligram dose regimen that you administered at 12 months. It's quite remarkable. And as you mentioned, even the 2 patients that didn't quite meet the remission criteria, they were just outside the required MADRS rating. So as a follow-up question, though, for Amir in particular. Impressive as this data is, how would you address skeptics who say that, yes, but the sample is a population that generated this data, 7, it's very small and may not be representative of the target population at large. So maybe the jury remains out.

Yes. I mean, fair question, and this is not something that we haven't asked ourselves. We asked ourselves internally and we do that. We challenge ourselves. We convince ourselves first before going out and sharing data with folks. So I'll give you the same answer that I give my team, which is, well, data are limited, but not all data were created equal. Some data are more impactful than others. And even with small numbers, you can't have highly impactful data. And my favorite example is think of an adverse event like suicidality. Those 7 patients who went into remission at 1 year. God forbid, if all 7 of those patients had suicidality at 12 months, would we dismiss the data and say, no, only 7 patients. So small numbers, it doesn't really mean anything. Actually not. Everybody would have sat up and took notice because suicidality is quite dramatic, it's quite important, it's quite impactful. In the same way, people who've been taking antidepressant medication for years, for decades, have not gotten better. They received 2 doses of study drug. And even with only 7 patients, 7 out of 7, though, are -- they don't have any depression at all. Those are pretty powerful data. So yes, I agree. Those are small numbers, but because they are such impactful data, those data are so impactful, it kind of makes it pointless how many numbers we have. Even if I had 5 patients and they were all in remission, I would have sat up and thought, okay, yes, this is something we can invest a lot in. I would throw the kitchen sink at it and get the drug into the market as soon as possible.

All right. And obviously, there's -- even with that small population, it's statistically significant and it seems clinically significant, too.

Clinically significant, absolutely. I mean at the end of the 12-month follow-up period, the average improvement in MADRS scores was 23 points. Now when you put that in the context of what is considered to be clinically meaningful by most experts worldwide, it's about 2 to 3 points on the MADRS. It is 23 points. So it is pretty huge.

Yes. Amazing. Okay. So let's move on to the Phase III program, which you've titled 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 do you anticipate the first dosing to happen and the targeted readout timelines you have at the moment?

Yes, absolutely. So we named our Phase III program, PARADIGM to represent the shift in treatment paradigm that we believe this drug will bring on from daily dosing drugs that address only the symptoms of depression to intermittent limited dosing drugs, which fundamentally changed the course of these, change people's patterns of thinking and are not chronic treatments at all. So that's why we called it PARADIGM. And within PARADIGM, we've got 3 pivotal studies. There are 2 short-term double-blind, placebo-controlled, randomized trials of 12 weeks in duration. And these are followed by -- one of those studies is a 2-arm study called APPROACH, and the other is 3-arm study called EMBRACE. And these 2 studies are followed by a long-term extension called EXTEND. So we are kicking off APPROACH. We've kicked off APPROACH. We've announced this in the press already. And any day now, we will have our first patient enrolled in this study. APPROACH is a 2-arm study, as I said, it compares 16 milligrams versus an inactive placebo. We will enroll about 110 patients per arm. After randomization, people will receive 2 doses of the study medication, which is the 16 milligrams of placebo, 3 weeks apart. The primary endpoint will be at 6 weeks. This is a traditional depression endpoint. So at 6 weeks, we will assess efficacy using MADRS, which is, again, a standard endpoint. But we also will follow them up initially for a secondary assessment, a secondary endpoint at 12 weeks until which time, the study will remain double-blinded. Now every patient that completes the 12-week double-blind period is eligible to roll over into the EXTEND study. And in the EXTEND study, we follow up patients for up to a year. Now the purpose of EXTEND, and I'm jumping to EXTEND before I talk about EMBRACE because traditionally, the agency has not required responses to long-term studies to demonstrate maintenance of effect or durability of effect. But more recently, and we've seen this with SPRAVATO as well, they've started asking sponsors to look at how durable a treatment effect is. And that is done by means of a study called a randomized withdrawal study, that's the most standard design. The way randomized withdrawal study is done is you give patients the test medication or the drug continuously. And then you randomly withdraw a drug from a sub population, a subgroup, and let the other group continue on the drug. And then you compare whether withdrawal of the drug results in relapse or precipitation of the symptoms. Now that's a very good design for drugs that are given daily. But for something that's given only once or twice, you can't really do that. And working with the FDA and our internal team and KOLs, we've come up with the EXTEND study design, which on Phase value, it appears to be a simple long-term extension, but the beauty of that study is and how we assess time to relapse in that study. So patients who roll over from APPROACH into EXTEND will remain in a double-blind manner following up in that study up until a point that we see that -- or any patient requires a treatment up until a point that they relapse. Now of course, if they have not responded anyways, those will be different patients. Some -- most of the placebo patients would be nonresponders when they get into EXTEND. But those who respond and roll over, they stay in the study, we follow them up, we do assessments every month of efficacy. And at the 12-month time point, we'll figure out how long they respond or how durable the response was. But EXTEND also gives us -- so this will be the durability of the initial treatment, the initial to treat. What EXTEND also allows is the opportunity for people for additional dosing if they require it. So anybody who relapses, had initially responded and relapses, they will have the opportunity to receive 2 doses of CYB003, 3 weeks apart. And there's also, of course, a provision of one top-up dose. So a maximum of 5 doses in a year. But as we see from the 12-month data that we've just shared, that proportion of patients who require additional dosing is likely to be small. But we'll figure out how many doses are required in a year to keep people in a remission -- state of remission. So that's APPROACH leading on to EXTEND. And APPROACH is the 2-arm study. Then we've got the 3-arm study, which is EMBRACE. EMBRACE compares -- EMBRACE has 16 milligrams. So the 2 doses, 16 milligrams and an intermediate dose of 8 milligrams, which is given again 3 weeks apart and an inactive placebo. So it's a 3-arm dose response kind of study, exactly the same design as APPROACH, 110 patients approximately per arm. And a primary endpoint at 6 weeks and a secondary endpoint at 12 weeks. Again, all participants who complete the double-blind 12-week treatment in EMBRACE are eligible to roll over into the EXTEND study where -- depending on whether they need it, they will be eligible to receive additional treatment. So that combination of APPROACH and EMBRACE, both are nested into EXTEND will give us the necessary data set, which will allow us to provide information to the agency on the efficacy, on the acute efficacy. So how quickly the drug will add, how soon people will go into remission and respond and how long that treatment effect will last. And those data will be required by the agency for a new drug application. We've been planning this meticulously and if you wish, we can go into the details of what measures we are employing in this study to make sure this is watertight and gives us the best quality of data. It will kick off APPROACH first. This will be followed in about 12 weeks' time with the EXTEND because patients need to roll over after 12 weeks. And then next year, we will start EMBRACE. APPROACH will be conducted in approximately 36 sites in the U.S. and Europe. We'll have 26 sites in the U.S. and then another 10 sites in Europe. So not a lot of patients per site, and we've done that on purpose. It's about 7-ish patients, 7 to 8 patients per site. And we've done that on purpose because we -- these are intense studies. And we want the sites and the investigators to be able to dedicate those resources to the patients and to the conduct of the study so that we get good quality data. So I'll pause there. If you have any further questions, that's quite a lot with the APPROACH, EMBRACE and EXTEND.

All right. Well, thank you for that. Great detail. So what role does psychiatry play in all these studies? We have been used to the term, assisted therapy. So maybe you could pull us out on what your thoughts on that?

Absolutely. Yes. So the first thing to state is that we do not do psychedelic assisted psychotherapy. And the reason is quite simple, because it is impossible to do psychedelic assisted psychotherapy with this drug. And why is it impossible? We can go into the technical details but suffice it to say that when patients are experiencing an acute psychedelic experience during the dosing session, their emotional cognitive state is such that they cannot participate in any psychotherapy. Simply speaking, the circuits in their brain are disrupted, including the language and speech centers, which are necessary both for them to understand as well as to interact. And that is not possible because of that state. We advise our participants to focus attention inwards. We give them an eye mask. We give them noise canceling headphones, so they block out every and all external influences. And they focus all their attention inwards because the work that needs to be done is internal. Now having said that, it would be irresponsible of us to not give them the adequate support that they need in terms of psychological support, both during, before and after treatment. So we employ what we believe is good in medical practice. And good medical practice dictates that for any patient that comes to a clinician and is going -- undergoing a treatment or a procedure, the clinician needs to inform the patient what procedure it is, needs to educate the patient, tell them the pros and cons, other options available. What will the treatment involve, what sort of benefit could be expected, is there a chance you will not get any benefit. What could be the adverse sequelae, what could go wrong, how do you handle situations that could go wrong. And stuff like -- and establish a rapport with the patient because if the patient is not -- you don't have a rapport, then you can't really do anything. The patient does not trust you, you can't really do anything with the patients. So that's what we do in the pre-dosing sessions with 2 study monitors who are qualified based on what the FDA have provided in terms of the required credentials. And that sets them up nicely for the dosing session. In the dosing session, we, of course, have the session monitors in the room. Now we've long held the view and the FDA had set previously or rather the field, in general, interpreted the FDA guidance that 2 people needed to be physically in that room while a patient was being dosed. We do have clarity now, and I believe other sponsors have clarity as well that the requirement is for 2 people to observe, and only if one needs to be physically in the room during the dosing session, one could be a remote monitor watching through a video, video cam or remotely and be available immediately to help or intervene as necessary. So that's the model we are employing as well. Then during the session, all the session monitors or the therapists do is provide support as needed. There could be a situation, both physical as well as psychological that may need help. Some people vomit. They feel nauseous. They need help. Some people may feel a bit anxious, and they may need some reassuring. So the session monitors are there in the room for both physical and psychological safety. They are not doing any therapy. In the first dose period, again, just like good medical practice dictates, we provide post procedural care to our patients. We debrief with the patients. The session monitors and the patients discuss what happened during the session and how best to maintain those treatment gains that they may have achieved during the session, just like you would do some physical therapy after you've had surgery. So it's a psychological rehabilitation in that sense after a procedure, that's nothing short of psychological surgery in that sense. I'm not talking about psychosurgery because that is taking us down a very different path. But yes, so it is as kind of dramatic what happens in that session, and you need to provide your patients with the adequate care. So that's really the rapport within which the framework, within which we help our patients. We provide them with psychological support. We have developed what I call, a Rolls-Royce version or you can call it the Cadillac version of psychological support framework, which is called as EMBARK, which is evidence based, and it is recognized by the experts in the field as something that is more or less like a gold standard. It does not prescribe any specific type of therapy but provides a framework through which people can be helped. And I can also say that we have made this available, some of the testers or foundational models, we've made them available online for free. Anybody can register and see what those models or what happens during those sessions and what is expected of the session monitor. They're on our website, there's a link and anybody can go and see that.

Thank you for that detail again. So the single most important concern that the FDA had with the conduct of Lykos is MDMA-assisted therapy development program was functional unblinding. So can you detail the steps that you are taking in the conduct of PARADIGM, in the conduct of the PARADIGM trial program to satisfy the FDA that it will not be an issue when they come to review your NDA submission.

Yes, absolutely. So first things first, and maybe you already understand this, but the issue of functional unblinding has not suddenly surfaced in clinical trials. We have been seeing these issues with functional unblinding for decades ever since drugs were being studied. And any class of drugs you take in CNS, in psychiatry, well also in non-CNS indications, most -- some of the trials, for example, in oncology, you can't really do double blind, you have to do open label. But in psychiatry and mental health, functional unblinding is not new. It occurs with sedatives, hypnotics. You can't really take a sedative hypnotic and not know you are sleeping. So functional unblinding takes place, antipsychotics, antidepressions, all classes of CNS drugs, it happens. And therefore, it happens with psychedelics as well. There's no denying there will be functional unblinding. All you can do is accept and mitigate the effects of functional unblinding, which is all the FDA is asking us to do. And we've been in close discussion with the agency. We've been working with them as part of our BTD. We have the privilege of being able to interact with them more frequently and more in depth than we would have otherwise had the opportunity to. So we've discussed the measures with them, and we are doing a few things. Firstly, we are using remote and independent raters. So people who assess efficacy are somewhere else, video, audio and they have no knowledge of what treatment assignment the patient has, whether it is their screening visit or their baseline visit or it is their 12-month visit, they have no idea what visit it is. All they are doing is making an assessment based on the MADRS. So that takes out a large element of potential issues due to functional unblinding. We are also doing something that we thought was important, even though the FDA have not asked us to do it, but we think it is important to do, which is the firewalling of what happens during the dosing sessions. So when the session monitors are sitting there with the patient, they will obviously see what the patient is experiencing, and they will know whether the patient is receiving the study drug or not by and large because it's still possible to get it wrong. When we have gotten it wrong in the past, which is a story for another time. But it is possible in a double-blind study, even with psychedelics, to get the treatment assignment wrong. So the therapists in the room, the session monitors will know. But those monitors are not involved in making any assessments of efficacy. They don't rate the patient on the MADRS. But also, they are instructed not to discuss anything that happened in the session with the principal investigator and other site staff because the principal investigator also has to make a global assessment of improvement in the patient's condition. So the rest of the site staff is firewall from what happens in the dosing sessions. The monitors, session monitors record everything that happens during the session, and it is entered into a separate case record form, which is only accessible to them or to an unblinded monitor. We are also incorporating design element in our program that the FDA also recommends could address potential functional unblinding and also some issues with competitors, which is using a dose response study. So EMBRACE is one of the studies, which by using a dose response format addresses some elements of functional unblinding. And I think more importantly and something that we don't often speak about enough is not just the functional unblinding is not the only thing that needs to be taken care of. It is also managing expectations. And they all raised expectations in this class of drugs. So we do a lot to manage expectations during the predose period, telling participants that this is an investigational drug. And with an investigational drug, you still do not know it works. And what we've seen in ritualistic and spiritual use of this class of drugs may not necessarily translate into this class of drug. So you temper their expectations. And by doing that also, you address some of the issues with potential functional unblinding. So we are taking a multipronged approach, which has been incorporated into a program, has been discussed with the agency. And we believe all of these measures will help mitigate the concerns people may have with functional unblinding.

And assuming that, I presume a large part of the population that you're enrolling will be psychedelics naive?

By and large, this population will be psychedelic naive, but one has to recognize that the use of psychedelics and experimental use outside of controlled settings is growing. People are desperate. There is a significant unmet need. We talked about the 300 million earlier. There are treatments that are not helping those patients. And people do not want to wait. Why should I wait for 5 years for a drug to come to the market when I can actually take some action even if it is something that may not be done in the right way. You may not have the desire outcome, people want to experiment. So there will be a small proportion of people who will get into the trial, may have prior experience, but it's only a small proportion. It will be representative of the general population. We will cap it. And you also cannot do a study which is not representative of the general population. You have to be able to generalize your findings. So we will cap it at levels that are seen in the general population. We have exclusion in our protocol, which screens out patients who traditionally, you would call a psychonaut. People who regularly have taken large doses of psychedelics in the past. So we screen them out as well. So yes, most of them, not experienced naive. But a small number representative of the general population will be included in our drugs.

Okay. Thank you very much again for that detail and clarity. So Doug, you've mentioned that you would like to make an NDA submission on a rolling basis. Does that mean you could start making the submission after the APPROACH study readout sometime in 2026?

Our goal, Robert, is, of course, to take full advantage of the breakthrough therapy status that we have. So that does enable us to submit a rolling submission and seek a rolling review. We're assuming that the FDA will be -- we'll comply with that and be happy with that. As part of our breakthrough therapy designation, we're actually obligated to design the most efficient program. So the pressure's on us as well as FDA. But what it does mean is that we can file certain sections of the NDA as they become ready and available. So nonclinical work, CMC and manufacturing pieces, clinical pharmacology and then, of course, the clinical outcomes from APPROACH and EMBRACE and EXTEND as well. So we hope that by doing that piecemeal, it kind of spreads out the work for us, but it also spreads out the review work for FDA as well. And it means that we should overall speed up the review process. But we'll also learn things along the way, that continuous communication with FDA means if any issues arise, we can address them in real time and not wait until the end for like one big review at the end. So that's certainly our goal, and we hope that FDA will agree with that.

Great. So at the end of the third quarter of this year, your balance sheet, Cybin's balance sheet carried about -- carried CAD 154 million, which is today's rates, I guess, is around USD 110 million. So you have in cash, you have no debt. So how far does that take you with respect to funding the Phase III program?

Yes. We expect current cash availability to get us through the top line Phase III data for CYB003 in 2026. We know everyone is excited about seeing this data. We just started the program. As Amir said, we kicked this off just about a week ago, and we are already screening patients. So we'll have the first patient dose I think pretty quickly. With 36 sites recruiting 220 patients, 6, 7 patients per site, we think that's a pretty manageable number. And we hope it's a reasonable screening goal so we should get to the finish of that top line data pretty quickly.

Great. So in the first quarter of next year, you're expecting to release Phase II data readout for CYB004, which is your deuterated DMT program for generalized anxiety disorder. So let me ask you a few. Does the company have the capacity both operationally and financially to manage 2 Phase III programs at the same time?

Well, listen. Let's not get ahead of ourselves. First of all, we have to see what the data shows. We are very excited about CYB004 and the profile that we're seeing. But this is our first test of this formulation in patients. So we have to always be a little bit cautious, not get ahead of ourselves. But we're already starting to see in this study the kind of PK/PD profile that we would expect. So a rapid onset of effects within 2 or 3 minutes, a treatment duration of around 90 minutes with patients spending most of the time in the tail of the experience post peak, which is what we were aiming for. So things are looking good, and we'll see when the data comes available. I mean, financially, our priorities lie absolutely with completing the CYB003 program and getting that through, that program to an approval. And I think when it comes to CYB004, we'll see what the data shows. And we have a number of options to think about how we move that to that next phase.

Great. So Cybin, I think, has delivered really a chain of positive news flow for some time, which does not seem, in my view, to be reflected in the share price. So what do you think the investment community is missing?

I think there's still a lot of skepticism around the sector as a whole, not just Cybin. I don't think we're being singled out in any way. When I look at our market cap, $220 million or so, an enterprise value of what, $70 million or so. It's kind of ridiculous based on the data we've shared and the fact that we're a Phase III company now. But that said, the market caps of our peers are not that much better either. And I think it's a level of skepticism with psychedelics as a whole. I think we've seen fairly small data sets so far. And I think the market is always looking for a larger, more robust data sets. But you also have to remember that we've been told for decades that psychedelics are bad. And now we're coming out with data and telling folks that, actually these treatments are really quite good for you if they're used in an appropriate way. And that message is going to take some time to get across. We're also in a period here post-election where there's a lot of other news going on. It's pretty hard to get attention. It's pretty hard to get eyeballs at this particular point in time. But we are heads down, continuing to execute clinically and of course, continuing to work hard to get our story out there and share the data that we just released more broadly.

Okay. So a final question here. We're going to have a new administration installed in the U.S. on January 20 next year. And there's been a lot of positive noise around the impact for medicinal psychedelics, particularly surrounding the Trump nominee for Health and Human Services Secretary RFK Jr. What are your expectations of the new administration with respect to its approach to psychedelics? And do you have any plans to engage with RFK Jr. before January 20?

First of all, I think we can agree that mental health issues, the mental health challenges that we're having in our country are a bipartisan issue, not -- and both sides of the aisle have been supportive of new treatments and actually, both sides of the aisle are supportive of psychedelic research. So that's good. Look, I'm kind of excited to see the level of enthusiasm and energy around this incoming administration and the apparent desire of these new incoming leaders of the health care part of government to make change and to bring improvements and to bring efficiencies. So that, I think, is a good thing. You don't create efficiencies and you don't speed up drug development by slashing resources, right? So I don't see that there's going to be some big cutting of FDA, which would have a negative effect than a positive one. And also encouraged to hear RFK's comments that he sees -- he's positive around psychedelics. His own family has had benefits from psychedelics. But he doesn't see -- he said publicly, he doesn't see these compounds being available in a retail store. He sees a regulatory framework around them to make them safely available to patients, which is exactly aligned with what we're doing as well. So I'm not seeing any negatives, perhaps slightly positive, and certainly no new hurdles coming with this administration, I think.

All right. Well, I think we'll wrap it up there. Thank you, Doug and Amir, for providing us with such detail about the progression and the plans for Cybin in the period ahead. If you have any other questions for either of them, please send them to me and I'll pass them on. For our analysis of the company, please refer to our open access website at www.watertowerresearch.com. The views expressed at this fireside chat may not necessarily reflect the reviews of Water Tower Research and are provided for informational purposes only. Finally, I'd just thank everyone for joining us, and have a great day.

Thank you, Robert.

Thank you.