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spk04: Good afternoon ladies and gentlemen and thank you for standing by welcome to SIBIN's second quarter fiscal year 2022 earnings call at this time all participants are in a listen-only mode following the prepared remarks we will conduct a question and answer session open to financial analysts instructions will be provided at that time for you to queue up for your questions i would also like to remind everyone that this conference call is being recorded today Monday, November 15, 2021, at 4.30 p.m. Eastern Time. I will now turn the call over to CYBIN's Vice President of Investor Relations, Leah Gibson. Ms. Gibson, please go ahead.
spk01: Thank you, Nadia, and welcome to CYBIN's second quarter conference call. This is Leah Gibson, Vice President of Investor Relations for CYBIN. With me on today's call is Doug Drysdale, Chief Executive Officer of CYBIN. And we will also be joined by our COO, Aaron Bartolone, Chief R&D Officer, Mike Palferman, CFO, Greg Cavers, and Co-Founder, Executive Chairman, and President, Eric So, for the Q&A session following Doug's remarks. Before we get started today, I would like to remind everyone that certain statements made on today's call relating to the company are forward-looking statements and are perspective in nature. In preparing these forward-looking statements, Several assumptions were made by Siben, and there are risks that actual results obtained by the company will differ materially from those statements. As a result, the company cannot guarantee that any forward-looking statement will materialize, and you are cautioned not to place undue reliance on them. Siben refers current and potential investors to the forward-looking information sections of its Management, Discussion, and Analysis available at CEDAR.com and on EDGAR at SEC.gov. Forward-looking statements represent SIBAN's expectations as of November 15, 2021. Except for that which is required by securities laws, SIBAN does not undertake any obligation to update any forward-looking statement, whether as a result of new information, future events, or otherwise. With that, I'll turn the call over to Doug.
spk08: Thanks, Leah. Good afternoon, everyone. And thank you for joining our business update call today. The past 12 months has been a period of rapid scientific exploration and progress for us. And we're thrilled to share our accomplishments with you today. At Cybin, we're on a mission to transform psychedelics into therapeutics. The need for safe and effective mental health treatments has never been greater. The pandemic has exacerbated the mental health crisis around the world, and we are dedicated to researching and developing transformative psychedelic therapeutics to improve treatments for all those who suffer. To achieve this, we have assembled a team comprised of world-class scientists, industry leaders, and external partners so that together we can push the boundaries. We are taking what we already know about classical psychedelics and engineering them with a goal of creating safe, effective, and commercially viable therapeutics for all those in need. We have evolved since our founding into a leading company in the psychedelic industry because we have and continue to evolve our entire ecosystem. By this, I mean we are focused on engineering proprietary drug discovery platforms, innovative drug delivery systems, novel formulation approaches, and treatment regimens for mental health disorders. I'll describe these in more detail in a few moments. Over the past 12 months, we have intentionally built out an ecosystem to optimize psilocybin therapy, always with patients in mind. We are working hard to create an infrastructure to support the scientific exploration and push the boundaries. Let me touch on some of our recent achievements. To date, we have developed a portfolio of over 50 novel compounds and have expanded our intellectual property to 15 patent filings across three patent families. This is a major differentiator for the company, and we anticipate that we will continue to add to our patent portfolio in 2022. Additionally, we have completed 74 preclinical studies, supporting the advancement of CYB3 and CYB4 toward clinical development, showing key dosing and bioavailability advantages over classical psychedelic molecules, with significant progress made in drug preparation with our partners. First in human studies are expected to begin in early 2022, subject to receipt of all necessary approvals. As a company, we have grown from five employees to 55 and now have a presence in Canada, the US, UK, and Ireland. And we are extremely proud of the fact that we are the first and only company in this sector to be listed on a New York Stock Exchange. Partnerships are also critical to accomplishing our goals. And in the past year, we have established 50 such partnerships with world-class scientists, and advisors, and clinical research organizations. Just recently, the U.S. Drug Enforcement Agency granted us a Schedule I manufacturing license for our Boston area research lab, allowing us to expand our internal research and development capability. And more recently, we received FDA authorization for our sponsored first-of-its-kind feasibility study using Kernel's quantitative neuroimaging technology, Kernel Flow, to evaluate ketamine's effect on brain hemodynamics using a wearable headgear device. We hope that this may allow for quantification of brain activity during a psychedelic experience. We also launched the Embark Psychedelic Facilitator Training Program in collaboration with the University of Washington. in preparation for the first clinical trial of psilocybin-assisted psychotherapy. We are co-sponsoring the study, which addresses COVID-19-related distress in frontline healthcare professionals. We're awaiting final approval in order to begin to initiate this study imminently. We're passionate about helping these healthcare workers, many of whom have suffered tremendously in caring for those gravely ill with COVID-19. and we created our EMBARQ psychotherapy program to support both therapists and patients. And lastly, we recently welcomed Dr. Amir Enamdar as Chief Medical Officer, Dr. Jeff Barton as Head of Research and Development, and Leah Gibson as Vice President of Investor Relations. The SIBIN team has done an extraordinary job advancing our promising approaches to developing safe and effective therapeutics for patients with mental health disorders. Today, I'd also like to share the meaningful advances we are making in our preclinical programs, notably CYB3. Our comparative preclinical data shows multiple potential advantages over classical psychedelic molecules, which we believe may have wide-reaching implications for the treatment of mental health. This work is especially urgent today, as nearly 700 million people globally are affected by some form of depression, addiction, or eating disorder, according to the World Health Organization. Some estimates indicate that anxiety disorders affect up to 12% of the US population. And that's why we're so committed to what we do. Turning now to our drug development program. We have made important scientific progress thus far and continue to add to that progress every day. In order to improve on existing therapeutics, we had to identify the challenges of the molecule itself so that we could address them. There is no doubt that academic studies and a recent phase two study have shown efficacy with psilocybin. Yet our goal is to transform these molecules into potentially useful and practical therapeutics that may ultimately receive regulatory approval, and with the aim of improving the safety profile and treatment protocols to benefit providers, payers, and most importantly, patients. We have had three parallel programs working on psilocybin for the past 12 months, two programs CYB1 and CYB2, looked at formulation approaches. And the third is built around our proprietary psilocybin analog, CYB3. The goal, of course, is to identify the best candidate at the lowest cost to take forward into clinical studies. All of this work is centered around addressing the known challenges of all psilocybin as a therapeutic. And these limitations include three issues. One, high variability in plasma levels, which means the potential for unpredictable patient outcomes, adverse events, and side effects. Two, slow time to onset, meaning patients often have to wait up to an hour and a half to achieve peak effects. And three, long duration of treatment, with some patients experiencing eight-hour clinic days resulting in limited scalability due to the increased time and resource burdens on payers, patients, and providers. We at Cybin believe that we can do better, and we're aiming to do so. We've learned a great deal through our extensive work on CYB1 and CYB2. In the case of CYB1, we selected a lead formulation prototype and made study supplies but the psilocybin release from the sublingual film was still greater than 10 minutes, resolving in the potential for more of an oral release profile than a sublingual release profile. CYB2, on the other hand, is a fast-dissolving oral formulation designed to improve the rate of psilocybin release. And while the dispersion occurred in just seconds, so a vast improvement, the oral nature of the formulation would still resolve in a long duration of action. As you can see, we've taken different approaches to try to overcome some of the challenges of psilocybin and to optimize where we make our development investment. Which brings us to CYB3, a proprietary deuterated psilocybin analog with improved properties. And in our view, cybin is the strongest candidate with which to move forward. We believe that we have a positive obligation from the patient perspective and in terms of delivering value to shareholders to advance only the most promising programs with the most efficient use of capital. CYB3 has been designed with the goal of achieving better patient outcomes, including less variability in plasma levels, faster onset of action, shorter duration of effect, and better brain penetration. We conducted many studies in multiple species with models of psychedelic action, studying pharmacokinetic profiling and following FDA safety requirements for the eventual advancement towards clinical use. All of this was done in order to predict a safe and efficacious human dose. What we found was that CYB3 has the potential to offer three main benefits. One, patient clinic days that are cut in half as a result of 50% reduction in both time to onset and total duration of treatment with CYB3 compared to oral psilocybin, providing for potentially greater access and scalability for providers and payers and patients. Two, approximately half the dose of oral psilocybin to achieve psychedelic effects due to almost two times brain penetration. This could result in less drug in the peripheral circulation and the potential for reduced side effects, such as nausea and headaches, which are commonly seen with psilocybin. And three, more predictable patient responses due to a 50% reduction in variability compared to all psilocybin, resulting in a safer therapeutic profile and the potential for reduced serious adverse events. All in all, CYB3 has been designed with the aim to retain all of the therapeutic potential of oral psilocybin while cutting the duration and the potential for negative effects in half. Importantly, and for the reasons I shared a few minutes ago, we also see this as an opportunity to combine MDD and AUD that is major depressive disorder and alcohol use disorder, into a single program with patent protection from a family of nine file patents. That lends itself to cost savings and efficiencies, and we believe has the greatest potential to deliver positive outcomes for patients. As for next steps with the program, we believe we have built a highly capable internal scientific team and have procured the external partnerships necessary to rapidly advance CYB3 through development. Our plan is to complete the full array of 32 preclinical studies by Q1 2022. Also in Q1 2022, we anticipate completing chemistry, manufacturing and controls, or CMC development, including the production of clinical materials. IMD, or investigational new drug, and CTA, or clinical trial application filings, are expected to be made with the U.S. FDA and the U.K. MHRA, respectively, in quarter two of 2022. Then, early phase clinical trials leveraging our innovative Embark psychotherapy program are expected to subsequently commence in the U.S. and the U.K. following regulatory approvals that quarter. We are very excited by these findings and are well prepared to advance the CYB3 program through these development phases, subject to receiving all necessary approval. And we look forward to keeping you apprised on our progress. The psychedelics industry is rightfully garnering a lot of attention for the groundbreaking work that is underway. The success of last week's Wonderland Conference in Miami is indicative of the promise and the passion in our industry and i believe we all came out of that conference even more confident that as an industry we can research potentially safe effective and accessible psychedelic treatments to patients we believe this is strongly supported by our expectations for cyb3 as well as a look into the first clinical data that has been reported on oral psilocybin from one of our peers we welcome and are excited for about the advancements being made in our industry. Yet we are all too aware of the improvements that still need to be achieved to evolve psychedelics into therapeutics. And that's why we are so excited about the potential for CYB3. Turning now to our financials. As of September 30th, 2021, our cash and cash equivalents totaled $75.2 million. Our net loss was $17.6 million for the quarter ended September 30th, 2021, of which non-cash expenses totaled $6 million and cash-based operating expenses totaled $11.6 million. Thank you for your time and attention today. As we continue to experience the lingering effects of the COVID-19 pandemic, it's absolutely urgent that we work to address the devastating impact of mental health disorders in an ethical and safe way. I'm proud of all that Cybin has accomplished towards its end, and I'm optimistic about our ability to move the needle and work towards researching and developing safer, more effective treatments to all who can benefit. We'll now open up the call for questions from our analysts on the line. Thank you. Operator?
spk04: Of course, if you would like to ask a question, please press star followed by one on your telephone keypad. If you choose to withdraw your question, please press star followed by two. When preparing to ask your question, please ensure that your phone is unmuted locally. And our first question today comes from Charles Duncan of Cantor Fitzgerald. Charles, please go ahead. Your line is open.
spk11: Super. Thanks. Good afternoon, Doug and team. Thanks for taking our question. And congratulations on the good progress recently. I had a couple of questions about the recent data that came out of Compass. And I guess I'm wondering, you know, you've described a target product profile that looks pretty compelling, but the data came after your design of CYB003. So as you parse the recent data release, and I know it hasn't been presented yet, but If you consider that data and think about not only a next-in-class but perhaps best-in-class profile, as you've described with 003, what gives you confidence in terms of the preclinical profile that 003 can really fit the bill? And are there any particular observations in that recent data that make you really intrigued with the profile of 003?
spk08: Hey, thanks, Charles. Appreciate the question. That's good to hear from you. You're absolutely right. The data that came from the COMP360 study was compelling. But no real surprises, I have to say. We've known a lot about psilocybin for quite some time. We've known and thought that it had great potential for efficacy, but with some limitations. And I think the study confirms that. It confirms that psilocybin is clearly effective in depression, and I think that's good for all of us. But when we look through the data, I think there's a number of things that are confirmatory of our strategy with CYP3. The first is when we look at side effects. About 30% of patients in this study experience nausea or headache. We've known this about psilocybin for some time, and we're hopeful that an ability to dose half of the drug level with CYB3 might lead to a reduction in those side effects. We saw, and I think this was noted much in the press, some concerning serious adverse events, including suicidality or self-injury. And while those may be associated with the patient group, there's also potential that it could be associated with the wide degree of variability that is seen in plasma levels with psilocybin. And so the ability to reduce that variability significantly, at least if nothing else, goes a long way, I think, to try to address some of those potential serious adverse events. And then I think the third aspect from the study is when we look at the data, I've seen these comments that perhaps the durability of the effect was not as robust as some were expecting. And that may mean a need for repeat dosing. It may not be a one dose and done. It may be that patients need two doses or three doses. And we'll see as we get through more clinical studies. But one thing we do know is that if repeat dosing is necessary, then having less time in the clinic, half the time in the clinic, is certainly more conducive to that kind of dosing measurement. So I think that what we're seeing from the data is really encouraging. I think it gives us great confidence in terms of efficacy. And what we're seeing in the properties of CYB3 is an improved pharmacokinetic profile. And the good news is that pharmacokinetic profile that we've taken through multiple species, we believe have high confidence will translate directly into a similar PK profile in man. Thanks for your question, Charles.
spk11: Yeah, that's super. One quick question in terms of this path forward and then an add-on in terms of IP. With regard to... given the target profile that you mentioned and given the data that you've seen out of the top 360 program, as you think about the path forward, would you imagine it to be capital efficient and perhaps more capital efficient than perhaps you would have assumed maybe even a week or so ago? especially given the profile of 003 and an ability to move quickly from, you know, first-in-man studies to efficacy to registration?
spk08: Yeah, you know, I think in terms of drug development, we couldn't be in a better place in that the core of the molecule, you know, of our analog, you know, psilocybin, has just been shown to be efficacious in a Phase II study. So what a great place to be starting from. often that is overhanging and there's a rush to proof of concept. We're fortunate that we can optimize the molecule. So I think we can move quickly now once we get through the IND process to some quick PK studies to confirm the PK profile and then quickly into dose escalation studies in patients with MDD. I think it gives us a fairly rapid path to move to proof of concept quickly after that. And then you had a question on IP.
spk11: Yeah, just quickly, Doug, and appreciate you taking all the questions. It seems like, well, pretty interesting that you could deuterate a compound and get rapid absorption and less variability. And so my question is, do you think that you're able to make non-obvious observations about the profile that could result in new chemical entity type IPs?
spk08: Yeah, we definitely think that this molecule is a new chemical entity. So far, we've filed nine patents in this family around this substratumine space, and so we expect some strong protection and more patents to add to that. I will say that the deuteration provides quite a lot of benefits. In addition to creating some metabolic stability, which helps to remove some of that variability, Dehydration also significantly enhances oral bioavailability and helps improve brain penetration. So all those factors contribute to the lower dosing and the quick onset of CYP3 that we see.
spk11: Appreciate the added color. I'll hop back in the queue.
spk08: Thank you, Giles.
spk04: Thank you. Our next question comes from Suman Kulkarni of Canaccord. Suman, please go ahead. Your line is open.
spk10: Good afternoon. Thanks for taking my questions. First, it's a clarification question. Is there anything else that needs to be gleaned out in preclinical trials before you can say that you're 100% taking 03 into clinical trials, or has that decision already been made?
spk08: Hi, Suman. It's good to hear from you. Yes, we're confident at this point that CYB3 is our lead candidate to move to clinical studies. We have about 10 preclinical studies that are ongoing to be completed, materials in place and CROs in place. So we're confident around the timing. We expect to complete those in the first quarter and then move to an IAD filing shortly thereafter.
spk10: Good to hear that. So on any preclinical comparisons that you could make on the intensity of the psychedelic effect of zero three versus oral psilocybin and how that might translate to a therapeutic effect in clinicals.
spk08: That's the question beyond my technical capability. I don't see if Mike is on the line. Mike, are you available to answer the question about animal models and psychedelic action? I think we're missing Mike, Suman. So maybe we can take it offline and we can follow up on there and we can look into some of the studies that we perform.
spk10: And then I have a last one. Given that 03 is a new chemical entity and will require the full clinical trial pathway, any kind of comments you could make on spending outlook behind that? Thank you for the question.
spk08: Go ahead, Doug. I will say that as we've combined NDD and AUD under a single program, then that leads itself to efficiency. We don't know precisely yet from regulators what the total safety exposure numbers will be, but clearly by combining two indications under one molecule, that's ultimately going to lead to some savings. I'm also hopeful and expectant that As we move through the program, we will be taking advantage of every option we can to accelerate development through breakthrough therapy designations or fast-track designations in other jurisdictions. And that, of course, ultimately leads to faster, more efficient development. So I do think that combining the programs and the nature of these programs leads to fairly efficient drug development compared to some product-based treatments.
spk10: Got it. Thank you.
spk07: This is Mike and I apologize. I had a technical challenge to answer the question with regard to comparison between psilocybin and the CYB003 on its potential psychedelic properties and therefore therapeutic properties. There is an animal model that one can use in mice and there you can compare the efficacy of both compounds and then relate that to the blood levels of the compound and that model has been shown to be translational in the sense that it correlates well with the psychedelic response to what you would see in humans for a variety of different psychedelics. That data confirms that the efficacy is similar, meaning it's got the same peak height, but the dose response is in favor of the more active compound in terms of its pharmacokinetic properties being more suitable, as we've described, for therapeutic benefits. So again, it's an animal model, but it is known to correlate with a clinical response. Thank you.
spk04: Perfect. Our next question comes from Patrick Truccio of HACI Wainwright. Patrick, please go ahead. Your line is open.
spk05: Thanks. Good evening. I have a few questions. I guess the first follow-up question I have is just based on, you know, if everything goes to plan, when would you expect to have the phase one data reported? And to what extent would you expect the animal data you've generated to translate to humans in the phase one trial? just in terms of the potential points of differentiation you've pointed out versus other psilocybin-like compounds.
spk08: Hey, Patrick. Thanks for the questions. I think in terms of the phase one data reporting, assuming we start to dose around the end of the second quarter next year, I expect that we'll have some good dosing data, so PK and escalating dose data around the end of 2021, early 2022, most likely. So fairly, fairly quickly. And in terms of the animal data, I think one thing that's really unique about the situation that we're in is that you'd be waiting on proof of concept to sort of confirm efficacy, which is the hardest thing to translate, right? And from animal models, from man, from CNS and psychiatric disorders. Here we have that sort of analogous data in the recent Phase II study. So what we're looking for is to translate pharmacokinetic properties, which we've already seen with a consistent pattern across three species already. And so we're pretty confident that that will translate into men.
spk05: Yeah, that's helpful. And then just based on the preclinical data that's been generated to date, do you have an idea of what doses you could evaluate in the CYB3 clinical development program And would you anticipate perhaps having a cohort in the phase two portion that may evaluate multiple doses of CYB3 perhaps spread one or two weeks apart along with the single dose cohorts?
spk08: Great question. So right now, we haven't decided the final range of doses that we will study. We'll lock that down in the very near future here. But it's likely from the data, preclinical data that we've seen, that the dose of CYB3 is around the half of what you'd see with psilocybin. And that's the range. But of course, that's the approximate range. We'll have to test that range, obviously, if you go through the dosing escalation studies. Sorry, what was the second question, Patrick?
spk05: Just in terms of, you know, maybe having a cohort with multiple doses in addition to having a single dose. Yeah.
spk08: Yeah, no, we think that's useful to investigate that. And as we're looking at phase two designs, that's certainly something that we're contemplating And one of the benefits of having, let's say, recent Phase II data out there is we've got some kind of leading indicators of what to expect. And so our team is already evaluating the potential by looking at multiple doses. I think it makes a lot of sense here.
spk05: Yeah. Yeah, I agree. And then just one last one, just a clarification on the IND to be filed, should we anticipate that the The program, the way it will be designed would be for CYB3. Would this be a study, the trial design, would it be a phase 1, 2A design where maybe you can move seamlessly from healthy volunteers into subjects in a phase 2A portion? Or would these be completely separate? And I guess, what are the advantages of maybe combining it in that way?
spk08: Yeah, you're absolutely right. And some of the benefits of working in two jurisdictions, both the US and the UK, is that we've built a supply chain in both jurisdictions, enabling us to work in parallel without having to ship Schedule 1 products across the Atlantic. And that enables us to work both in the U.S., where it's necessary for FDA, but also take advantage of some of the regulations in the U.K. that are a little easier. So it does mean that we can potentially create a nested study like that. and move through healthy volunteers into MDT patients fairly seamlessly. You're correct.
spk05: Terrific. Thank you very much.
spk08: Thanks, Patrick.
spk04: Thank you. Our next question comes from Francois Brisbois of Oppenheimer. Francois, please go ahead. Your line is open.
spk02: Hi. Thanks for taking the questions. I was just wondering, you know, maybe a difference between recent data from another company Can you just help us understand why the choice of NDD versus TRD and maybe expectations there in terms of the placebo effect and the treatment effect in NDD versus TRD?
spk08: Hi, Frank. Thanks for the question. You know, we've been committed to NDD from the beginning. And it's more of a clinical trial strategy than maybe. ultimate use. But as we think about the least risky path to proof of concept, NDD patients, I think, provide that, whereas some TRD patients might be quite resistant to any kind of therapy. And I think there's a bit of a misunderstanding or sometimes differential understanding of what TRD really is. And in some cases, these patients are Those that have just tried two or three SSRIs and maybe don't tolerate them. In other cases, it may be patients that really have tried many treatments and just don't have an effect and are resistant to treatment. So there's a difference, I think, between trying multiple doses and being truly resistant. Either way, I think to start out the first proof of concept efficacy study with the most resistant patients doesn't make a lot of sense. So we're starting with MDD. It's a larger population. We've seen, you know, if you look at the STAR-D study and other studies of SSRIs, that SSRIs have shown to be not much better than placebo over the long term in patients with mild to moderate depression. So this is a large population of patients that really need help, and that's where we would start. There's always an option to look at TRD somewhere down the line once we've got through the concept. In terms of placebo, you're right, I mean, Sorry, I was going to answer a second question. That's okay. In terms of placebo, you're right. There is a placebo effect in every depression study. And we've been working to evaluate how to best address that. Some of that comes from study design, but some of it also comes from the tools that are used to screen patients. And we've been working with group at Mass General Harvard Medical School on designing a using a tool that is a secondary screen so once the patients have been recruited by the investigator screened by the investigative team this second group on an arm's length basis would perform a further screen to make sure that absolutely right patients they get into they get into the study I think That's just an extra kind of belt and suspenders to make sure that the right patients are doing that.
spk02: Okay. Now, that's very helpful. And just on that note, on the placebo note, I think the placebo arm in these trials is always very interesting. Is it fair to assume that, you know, because you might be able to get similar efficacy, if not better, with a lower dose, can you share any thoughts that you might have on the placebo arm? Would there be danger of using a one milligram dose of the psilocybin analog if the efficacy might be larger here?
spk08: So the placebo debate is a significant one within our scientific group, and it's one of the major questions that we expect we'll have for regulators as we go into those pre-IND or scientific advisory meetings in the first quarter of next year. I think that's important to get their views on. I think one benefit of CYB3 over CYB1 is that we could potentially use a low dose. I'm not saying it's one milligram. It might be something lower than that, half a milligram, which was challenging with CYB1 because of the formulation. But that's certainly a potential that we'll evaluate, along with other options prior to this event.
spk02: Okay. And then if I could sneak just the last one in. There's just a lot of interest in the field right now. On the scalability front, you know, potential advantages with a quicker acting treatment, are you mostly trying to have an advantage on the scalability side based on the administration? Or is there, with the EMBARQ program, is there potential for scalability advantages on the PrEP and the integration phases of the psychotherapy?
spk08: Yeah, you know, I think the challenges to scalability are multiple fold, you know, The first is one challenge might be just adoption by clinic. At the end of the day, these treatments have to be administered somewhere in a clinical setting under supervision. And if you can't get depression clinics and addiction clinics to adopt treatments because they're too burdensome, then patients can't get access. Another aspect is reimbursement. If the supporting care around the molecule is... too expensive, like eight-hour sessions, then there's a hurdle there to reimbursement, which might limit access to some patients. So it's really about ensuring patient access. The Embark program, what we're doing there is making that program open source for therapists. We want to make sure that therapists are trained if they want to be trained in the Embark program and have access to the tools. So it's combining the the clinical networks with the training program and the molecule, bringing those together to form an infrastructure and ecosystem that can support patients.
spk02: Okay, that's it from me. Thank you very much. Thank you, Frank.
spk04: Thank you. Our next question comes from Andrew Parthino of Stifle. Andrew, please go ahead. Your line is open.
spk03: Hi, good evening. Thank you for taking my questions. Maybe first starting off with your CYV003 program. For your IND or CTA applications, could you walk us through how that's going to work with MDD and AUD? I imagine you mentioned that you could combine the program for two indications, one molecule, but at what point? Does it make sense to have two separate tracks of clinical trials if there is a point where it makes sense?
spk08: Yeah, thanks, Andrew, for the questions. Yeah, I think there's a lot of, there's a couple of different areas where it makes sense to combine under one molecule. First, obviously, is in the preclinical work where you're just doing one molecule. The second is in early safety and dosing work where we're looking to find the optimal dose. it's likely then that we would separate the MDD and AUD populations given the different needs that they have and maybe even different approaches to psychotherapy. For example, in alcohol use, perhaps group therapy would be a benefit. And then in terms of the overall exposure, the overall safety database, our open label exposure studies can contribute to both indications. So we see that there's synergies across the board, and we'll be looking to leverage data wherever we can for both indications.
spk03: Okay, thank you for that, Culler. And just sticking with CYB003 for a moment, you know, what's your, I realize it's early, but what's your expectation for repeat dosing with the data that you have thus far, or is it Is it similar to what we've seen with other players in the industry and other data that we've seen published? Or do you think that your molecule could be a little different here?
spk08: I think it's very hard to tell at this point in time. When you look at different academic studies with psilocybin, we've seen quite durable effects. The recent phase two study had perhaps less durability than was expected. So we certainly plan to incorporate multiple dosing into our future clinical programs. And the good news is if multiple dosing is required to have long durability effects, then we have a molecule that potentially has half the clinic time. So it makes that repeat dosing really a practical reality.
spk03: And on that train of thought, do you have any data or any indications on how CYB003 is an agonism for the 5H2B receptor? And any color on that given we've seen that receptor potentially having some negative effects on heart valves?
spk08: It's a good question. And I'm going to ask Dr. Palfreyman to talk about maybe the 5-HT panels that we've done.
spk07: Yes, that's a very good question. When we talk about repeat dosing, I wanted to stress that we don't anticipate this to be essentially a daily dosing. This is single doses at suitable intervals between them. And what we do know about the 5-HT2B receptor is and the valvopathy is that it's only really seen as a problem when you have repeat dosing to stimulate that change in the structure of the heart valves. So there's a mechanistic difference. And then what we do know is that this class of compounds do have some affinity for the receptor. So we are obviously going to, we do include in our preclinical studies and our safety studies looking at those types of risks. What we've seen and what we are very confident about is that the way we've designed our preclinical safety studies corresponds to this concept of repeat dosing, but not repeat every day, but with suitable periods between, if you like, individual single dosing. And there we essentially have, I won't say we've eliminated the risk, but the risk is certainly not appeared in the approach we've taken. So if we keep that in mind going forward, I think this is a risk factor that we all are very conscious of from historical data with compounds that do affect the 5-HT2B receptor. but we don't believe this with CYB003 and the way we use this compound, that that's going to be a deterrent to the type of dosing I've just described to you.
spk03: Thanks for that great color. And maybe just the last one for me, if I can fit it in here, maybe transitioning to CYB004. Do you have any color on that? realize that you haven't really talked about it as much as CYB003 thus far, but is there anything that you can share that could point to potentially this drug candidate being more suited to treat anxiety disorders versus what's existing on the market?
spk08: Yes, I can say, Andrew, that there's some relation between the work we've been doing on CYB3 and CYB4 in that they're both so some similarities in the work and some consistencies in the results that we've seen. In terms of progress, CYB4 is perhaps a quarter or so behind CYB3. We're prioritizing CYB3, but CYB4 is working its way through the preclinical program. It's always good to do these things in a slightly staggered way so you can take learnings from one program and apply it to the other. What I will say about current treatments for anxiety disorders, is that SSRIs are not particularly well-suited for anxiety disorders. You know, they're quite slow to have an effect, you know, six weeks or more in some cases for the patients. I mean, as much as a third of patients respond in maybe 12 weeks for SSRIs in general. And for anxiety disorders, that's a very long, long wait for someone whose life is disrupted by their anxiety. Also, some of the side effects of SSRIs, like weight gain and sexual dysfunction, again, particularly unsuitable for patients that are suffering from anxiety disorders. So what we're hoping with CYB4, given what we know about this tryptamine, is an opportunity to have a very rapid onset, a very quick onset of action and a robust and durable effect. But we'll share more on CYB4 as we as we work our way through preclinical program.
spk03: Thanks for that, Keller, and I'll get back in the queue.
spk08: Thanks, Andrew.
spk04: Thank you. Our next question comes from Elema Pyro of Roth Capital Partners. Elema, please go ahead. Your line is open.
spk06: Yes, thank you so much. Hi, Doug. So just to confirm, CYB4 is an inhaled formulation that you're working on, correct?
spk08: Well, CYB4 is a deuterated cryptamine that we're working on in the preclinical work, of course. We're not using an inhaled version of it. And in early, in first demand studies, we may not use an inhaled version of it. But that's our intention. It's just a great inhaled version of CYB4 to overcome some of the bioavailability challenges and deliver it very rapidly into the bloodstream. That's the plan.
spk06: Okay. And I probably didn't hear you correctly or clearly. You were talking about the first responder trial, and I think it was mentioned that in the Netherlands. Is this program with CYB3, or would you please clarify that a little bit?
spk08: Yeah, the first responder, I should say it's not first responders. It's frontline COVID health care workers. So those practitioners, those professionals that have been working to To battle COVID-19 for the last 18 months or so, they're facing burnout, distress, kind of a form of PTSD, I guess, as a result of that. The study is in collaboration with the University of Washington in Seattle. And this will be a psilocybin study. But of course, as you now know, that CYB3 is a psilocybin analog, we would see results to have a good correlation with the work that we're doing with CIDC.
spk06: Okay, okay. I think it's much clearer. Thank you. And last question is when you look at the Comp360 design and especially the relatively skimpy integration protocol that they had, I think they had two sessions, Do you think you can improve upon that, especially since you have or are thinking of multiple dosing?
spk08: Yeah, I will say this is something we feel quite strongly about internally. And as we've looked at other studies, academic studies, that have either omitted psychotherapy or reduced it significantly, the effects are less impressive. And the fact that only one prep session was used in the COM360 study may have contributed to the sort of lower than expected durability of effects. So our EMBARQ psychotherapy program uses three prep sessions, and we think it's important to get patients very well prepared for their treatment so that the treatment has the most impact.
spk06: Thank you so much, though. Thank you very much.
spk04: Thank you. Our next question comes from Sep Monetary of 8 Capital. Sep, please go ahead. Your line is open.
spk09: Thanks, and good evening, Doug. Congrats on the continued expansion of your footprint in the space. Obviously, you guys just got the D8 manufacturing license. I just want to get some color on what that opens you up to and if there's other labs that you have that you expect would also need to get that or if that's really the one license you need.
spk08: Yeah, thanks for the question, Tep. So we've been working with, as you've heard, many, many partners across North America and Europe over the last year or more, and across a range of different activities from synthesis to preclinical work to getting ready for clinical studies. And so we've been able to tap into this ecosystem of 50 or so partners that where necessary, have the right scheduled control substance licenses. So it hasn't slowed us down at all. But the benefit of having our own internal Schedule 1 license from the VA means that we can do much of the early discovery work internally. And that means a far more rapid turnaround from results to next iteration. and it also means reduced costs as well. It's just a more efficient way to do that work at that particular stage. So that's exciting that our internal team can push ahead and not have to rely on external partners to do some of that other work.
spk09: Got it, got it. So that kind of high-quality CGMP API you need for the trial, will that be kind of acquired at your own facilities, or is that more down the line?
spk08: So this is small scale laboratory and it's called manufacturing, but it's really for small scale use. We've already secured our supplies of CGMP level materials. As I mentioned, supply chain in the UK and US has been established that will be able to supply our clinical studies. So we've given ourselves the flexibility to work in multiple jurisdictions, but also importantly, having backup supplies so that we have options going forward for clinical supplies and for commercial supplies.
spk09: Awesome, awesome. Just one last question from me speaking in the multiple jurisdictions. I heard some mention of the potential for a pre-IND discussion. Do you plan to have similar discussions with the MHRA in terms of like an advisory panel? And do you think that there'll be a potential update to the market around your development plans and maybe the trial design and things like that coming to the back of that sort of discussion early next year?
spk08: Yeah, that's a good question. So we expect to reach out for scientific advice from the MHRA very shortly, actually, and hoping we can have discussions with them and with FDA in the first quarter. I think if those conversations, I expect they will, if they inform our decisions around clinical trial design then we can certainly provide an update to the market on that. Perfect. Well, thanks for the call today. Take care. Thank you very much, and thank you to everyone for all the questions. At this point, it's 5.30, and we all have to run to other meetings, so I want to thank you all very much for your time today. Take the time to listen to the business update and the questions. Thank you very much, and have a good night.
spk04: Thank you, ladies and gentlemen. This concludes today's call. Thank you all for joining. You may now disconnect your lines.
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