Good morning, ladies and gentlemen, and thank you for standing by. Welcome to Cybin's conference call and webcast. At this time, all participants are in a listen-only mode. Following the prepared remarks, we will conduct a question-and-answer session. Instructions will be provided at that time for you to queue up for questions. I would also like to remind everyone that this conference call is being recorded today, Monday, November 18th, 2024, at 8:00 A.M. Eastern Time. I will now turn the call over to Cybin's Chief Executive Officer, Doug Drysdale. Mr. Drysdale, please go ahead.
Thank you, Todd. Good morning, everyone. Thanks for joining the call today. This morning we shared what we consider to be truly remarkable 12-month efficacy data from the Phase 2 study of our lead program, CYB003, our proprietary deuterated psilocybin program in development for the adjunctive treatment of major depressive disorder, or MDD. Before we begin, please take a moment to note the cautionary statement language on Slide 2. This morning, I'll start by providing an overview of Cybin's innovative neuropsychiatry pipeline, the latest data from our CYB003 program, the ever-growing unmet needs for improved therapeutics to treat mental health disorders, and why our new data is nothing short of groundbreaking. Next, our Chief Medical Officer, Dr. Amir Inamdar, will discuss in full detail the 12-month efficacy durability measures that were observed and why this is such a significant achievement.
Amir will then share more detail about our recently initiated Phase 3 pivotal program evaluating CYB003, which we have named Paradigm. Following some closing remarks and a look ahead, we'll then open up the floor for questions. At Cybin, we continue to drive forward our clinical stage pipeline of serotonin receptor agonists with the aim of transforming the mental health treatment landscape. While our focus this morning is on CYB003, let me just say a few words about CYB4, the second lead program in our innovative neuropsychiatry pipeline. CYB004 is our deuterated dimethyltryptamine in intramuscular, or IM, form, being developed for the treatment of generalized anxiety disorder, or GAD. GAD is a life-threatening condition which we believe has the potential for breakthrough therapy status. We are progressing our Phase 2 study of CYB4, a short-duration treatment, and dosing is underway in a 36-patient study.
CYB4 has been designed to have a rapid onset of effects, around two to three minutes, and a short treatment time of around 90 minutes, which fits well within the current interventional psychiatry infrastructure. We believe CYB4 has the potential to provide rapid and sustained benefits, and we expect to share top-line safety and efficacy data in the first quarter of 2025. These next few months are shaping up to be an exciting and transformational period for both programs. Just a quick word here on why we're so focused on these two disorders. From the beginning, we have been thoughtful and intentional about our target indications. On this Slide, we summarize the large addressable markets for MDD and GAD, as well as the health impact and need for improved treatment options. MDD and GAD are indications with high unmet needs.
When you consider the staggering number of people who face one or more of these often devastating disorders, with more than 300 million people worldwide suffering from depression alone, it's clear why the need for improved therapeutic options is so dire. In MDD, two-thirds of patients don't experience relief with initial antidepressant treatment. And similarly, with GAD, 50% of patients do not respond to first-line treatment with SSRIs and SNRIs. And this is why we do what we do. Beyond MDD and GAD, we believe that there are additional indications in neuropsychiatry and CNS disorders that our pipeline has the potential to make a difference in. Studies have suggested that these tryptamine-based therapeutics could have potential clinical benefits across indications, not limited to depression and anxiety, but also bipolar disorders, addiction, eating disorders, for example.
We believe that our pipeline could potentially address indications that affect over 200 million people in the U.S. alone. Now, let's, let's turn to the really exciting data highlights. The headline here is that we're on the precipice of moving away from daily treatment of signs and symptoms of depression and toward intermittent and durable treatments like CYB003 that perhaps have the potential to change the course of disease. I don't think it's an exaggeration to say that we're quite possibly witnessing a pivot point in mental healthcare treatment paradigms and practices. It is nothing, nothing short of remarkable that 100% of participants receiving two 16-milligram doses were still responsive to treatment at 12 months. We're clearly seeing the potential for large and durable reductions in depressive symptoms with rapid onsets of effects.
This represents meaningful clinical benefits for patients, as well as the fact that CYB003 is an adjunctive treatment, meaning that patients do not have to titrate off of their foundational antidepressant medications before beginning treatment. In line with the positive four-month data we presented in March, we are thrilled that the effects are indeed durable up to 12 months. In short, our Phase 2 results have confirmed our hopes and our expectations that two 16-milligram doses of CYB003, administered three weeks apart, provides remission from depression symptoms for 12 months for the majority of patients. This shift is profound and exciting. We're moving away from the treatment of the symptoms of disease to changing the course of disease. As you will recall, CYB003 received breakthrough therapy designation from the U.S. FDA earlier this year.
Notably, this is the first known breakthrough therapy designation by the FDA for an adjunctive tryptamine-based therapy for the treatment of MDD. There are numerous benefits of breakthrough therapy designation. It provides an expedited review pathway, as well as increased access to FDA guidance on trial design, and has the potential to significantly reduce drug development timelines. Importantly, the designation acknowledges the urgent unmet medical need for more effective treatments of MDD and supports CYB003's potential for significant improvements over existing therapies. Our engagement with the FDA as we commence our Phase 3 Paradigm program has been invaluable. We believe that our Paradigm program incorporates appropriate protocols that proactively address some of the challenges encountered by peers developing molecules with similar mechanisms of action.
We feel confident that we are aligned on trial design, including measures to address functional unblinding and expectancy bias, and we see a clear path to a new drug application or NDA submission. Amir will have more to say about this shortly. Let me provide a little context here that I think will really illustrate how powerful these findings are. As you may know, we use the Montgomery-Åsberg Depression Rating Scale, or MADRS, as a clinical tool to assess the severity of depression. The MADRS scale is a widely used and FDA-trusted tool that's been around for some 50 years. Patients are rated before and after dosing by independent remote and blinded raters who have no knowledge of the treatment itself. Typically, with SSRIs, you see about a two-point improvement over placebo in reduction in depression scores.
With CYB003, we saw approximately a 14-point reduction in MADRS scores at the three-week primary endpoint from a single dose of CYB003 versus placebo. And at 12 months, we saw a mean change from baseline in MADRS of about 23 points for the 16-milligram patients who received two doses. Also on this chart, you can see the maximum effects of MADRS seen in pivotal studies used for comparators: SSRIs, atypical antipsychotics, and ketamine also shown here. We believe that our two-dose paradigm, which appears to further reduce depressive symptoms and improve both response and remission rates, is the right design to achieve durable effects. And we plan to continue to study this protocol in our Phase 3 paradigm program. Psychiatric care in the US today is overburdened, and access is significantly constrained.
Sadly, less than one-fifth of psychiatrists are available to see new patients, while average wait times for an in-person appointment exceed two months. Established intermittent treatments like TMS and esketamine can require up to 36 visits per year and sometimes more, which is taxing both the patients and to the treatment centers. A treatment with the potential to deliver both rapid onset and durable relief for up to 12 months after just two doses, like CYB003, has the potential not only to help existing patients but also to free up capacity to see new patients, thus lowering barriers to urgently needed care. Cybin has assembled a highly experienced leadership team that is focused and committed to achieving our mission of redefining the standard of care in mental health. Thank you.
As we progress our clinical programs, we have also expanded our R&D team with the addition of exceptional drug development leaders who bring a wealth of big pharma and CNS experience, including overseeing large, complex, global Phase 3 trials. We're lucky to have them on board while we advance our programs at this pivotal time, and we believe that we have the right team in place to pursue and deliver life-changing medications for mental health conditions. I'll now turn over the call to Amir, who will provide you with more details about these groundbreaking findings from our 12-month data. Amir?
Yeah, thank you, Doug. Good morning, everyone. It is, indeed a pleasure to share these extraordinary findings.
The sustained improvement in symptoms of depression at the 12-month mark after just two doses of CYB003 is truly remarkable, and it's a testament to the potential of CYB003 as a transformative treatment that can change the treatment paradigm for patients suffering from depression. As a refresher, or for any of you who are new to this program, let me provide some background. Our Phase 1-2 study was designed to evaluate the safety and efficacy of CCYB003 in healthy volunteers and in patients with MDD in a double-blind randomized placebo-controlled design in participants aged 21 to 65 years. In Phase 1, we assessed pharmacokinetics and safety of a range of CYB003 doses, and we identified a dose at which strong pharmacodynamic effects that could translate into a therapeutic benefit were observed.
Having identified a potentially therapeutic dose, in Phase 2 part of the study, we enrolled participants across three cohorts of 12 each, randomized in a 9:3 ratio, active to placebo at baseline. In each cohort, participants received two administrations of the study drug three weeks apart, and all participants received the active drug at three weeks, week three. Patients with MDD were at least moderately depressed, with a score of at least 21 on the MADRS scale. Patients were also required to be on a stable dose of antidepressant medication but were inadequately responding to treatment. Importantly, though, these were not treatment-resistant patients but perhaps representative of a larger portion of the MDD population. What we saw in the CYB003 study was the mean baseline score on the MADRS placed patients in the moderate to severe depressed range.
During the study, participants were provided with education, informed consent, and psychological support pre-dose, during dosing, and post-dose, consistent with good medical practice. After receiving the first dose on day one, participants were discharged from the clinical unit and came back three weeks later to receive a second dose, at which time point the primary efficacy of a single dose of CYB003 was assessed. We conducted a second assessment for incremental efficacy three weeks after the second dose. So this was done at day 42 or week six. We then assessed the durability of treatment effects at four months, which we announced previously, and at 12 months, which I am pleased to share with you today. This Slide shows improvement in depression as assessed using a change from baseline in MADRS total score at various time points after dosing.
We have previously shared this data from the four-month follow-up, which demonstrated a large and sustained reduction in symptoms of depression of approximately 22 points on the MADRS total score, with 75% of the participants in remission. Today, I am pleased to share with you data from the 12-month follow-up. At the 12-month endpoint, two doses of 16 milligrams resulted in an improvement in total MADRS scores of approximately 23 points, while this improvement was about 18 points for the 12-milligram group and just after two doses. We had initially not planned to follow up our patients for 12 months, but seeing the exceptional results at the four-month time point, we prepared a protocol amendment which followed up patients who were available and consented up to a year.
So by the time we were able to get the protocol approved and implemented, some of the 12-milligram cohort patients were already beyond their nine-month time point, and that is why you see some missing data here. What we did observe at the 12-month time point, however, is sustained improvement in symptoms with both the 12 and the 16-milligram dose. This translated into exceptional response and remission rate, and as a reminder, response conventionally is defined as a 50% more improvement in symptoms, and remission is defined as a MADRS score of 10 or less. At the 12-month time point, the vast majority of patients on both the 12 and 16-milligram groups had sustained improvement in symptoms. With two doses of 12 milligrams, 60% of the patients were still responders at 12 months, while 50% of them were in remission.
As you know, we are going to progress the 16-milligram dose in our Phase 3 studies, and we can look at the numbers with 16 milligram on the next Slide in a bit more detail. This Slide shows the response and remission rates for patients receiving two doses of 16 milligram, and what you can see is a consistent and sustained improvement in symptoms over time. Patients who received two doses of 16 milligram, 100% of them responded to treatment, and 71% were in remission at 12 months. The two patients that did not meet criteria for remission at 12 months had a score of 11, so basically just missed remission by a point on the MADRS. While these are small numbers, and we should interpret the results with caution, the significance of such large effects is huge despite the numbers.
And if these hold true in the larger Phase 3 studies, it would be truly transformative, as we have not seen these kinds of results with MDD treatments in the past. What is reassuring is that all of this has been in the context of a favorable safety profile. At the 12-month time point, no adverse events were reported. In the past, there have been some concerns with respect to treatment emergent suicidality with some drugs in this class. So I'm pleased to say that we did not have any reports of suicidality in our 12-month follow-up or at any point following dosing, as assessed using a validated assessment measure, the Columbia-Suicide Severity Rating Scale. We also did not see any adverse long-term sequelae of treatment.
We have previously reported a benign side effect profile in the six-week short-term study, so it is comforting to know that CYB003 is well tolerated in the long term, up to a year. We now look ahead to Phase 3. Following a productive type meeting with the FDA earlier this year, we have now initiated Paradigm, our multinational Phase 3 pivotal program. Our breakthrough therapy designation status has enabled a highly collaborative and thorough design and review process with the FDA at two separate meetings. We are thrilled to commence our Phase 3 program, Paradigm, which is meant to signify the potential paradigm shift in the treatment of mental health conditions with CYB003. This Paradigm program consists of two international multicentric short-term Phase 3 pivotal trials, Approach and Embrace, and a long-term extension study, Extend.
Each of the two short-term studies will have primary endpoints at six weeks and secondary endpoints at 12 weeks, at which time all patients that are eligible and willing will roll over into the extension study, where we will follow them for a year. During that year, we will allow for redosing either for patients who did not respond in the first two studies or who relapsed at some point. We've incorporated a number of features in our studies to mitigate some of the methodological issues in the conduct of studies with this class of drugs, including measures to address potential for functional unblinding. In addition to using remote, independent, and blinded raters to assess primary efficacy endpoints, we're going to include a dose-response study, Embrace, in our program. This approach has been recommended by the FDA to partly address the issue of functional unblinding.
We will also follow up our patients for a year, which is the time point that will outlast any potential expectancy effects. We are also firewalling our investigators from the effects seen in the acute dosing session. This will ensure that the investigator is not functionally unblinded to the study drug. We believe that Paradigm incorporates appropriate protocols that proactively address some of the challenges encountered conducting trials of this nature, so these include recruiting from a larger unrestricted MDD population, administering CYB003 as an adjunctive and not requiring patients to titrate out their existing antidepressants, and utilizing a 12-week blinded period to maximize the number of patients that remain in the study throughout the blinded stage. The next Slide depicts in detail our Phase 3 pivotal studies. As we said, Paradigm comprises two 12-week randomized placebo-controlled studies named Approach and Embrace, and a long-term study named Extend.
Approach is a Phase 3 randomized double-blind placebo-controlled international multicenter trial of oral doses of CYB003 to assess combined safety and efficacy in MDD. Last week, we announced that this study has been initiated, and top-line results are expected in 2026. This will be a two-arm study comparing two doses of CYB003 to two doses of placebo administered three weeks apart. The study will enroll approximately 220 patients across 36 clinical sites in the United States and Europe, so roughly about six to seven patients per site. This is worth noting that for the most part, these patients are psychedelic-naïve, meaning that they have little or no experience with psychedelics and therefore would not know what to expect.
The second study, Embrace, is an efficacy and safety study, again a Phase 3 multicenter double-blind randomized placebo-controlled study which compares two different active oral doses of CYB003 and one inactive placebo in eligible participants with MDD. This study is expected to begin in the first half of next year. Extend is a Phase 3 long-term extension with optional additional doses of CYB003 to assess the safety and long-term efficacy in participants with MDD. This study is expected to begin 12 weeks after commencement of Approach and will enroll patients from both the short-term studies. The Cybin clinical team has accomplished an extraordinary amount in a short time, and we are eager to continue investigating CYB003's potential to provide long-lasting relief from depressive symptoms.
As you can see, we are incredibly passionate about what we do and eager to continue advancing CYB003 towards regulatory approval and ultimately commercialization to give MDD sufferers a more patient-friendly and longer-lasting regimen for treating their symptoms of depression. I'll now turn the call back to Doug for some closing remarks. Thank you.
Thank you, Amir. I think you'll all agree that these findings are pretty transformational and truly validate the potential of CYB003 to disrupt the current standard of care paradigm in MDD. To summarize what you've heard today, improvements in depression symptoms were robust and sustained, with a mean 23-point reduction in MADRS scores from baseline at 12 months. Response and remission rates were durable. 100% of 16-milligram patients receiving two doses were responders at 12 months, and 71% of them were still in remission 12 months after just two doses of CYB003.
This is the most impressive remission rates we've seen so far in the sector, and all with a favorable safety profile. We believe these to be truly remarkable results, especially when compared to the current standard of care. At this 12-month mark, we have clear and compelling data that CYB003 has the potential to be an effective and safe adjunctive therapy, delivering durable remission and providing a clear clinical benefit with very infrequent dosing. With this positive data in hand, we are thrilled to have initiated our Phase 3 program as we work toward making a significant difference in patients' lives, so we've looked at this positive data through the lens of how patients can benefit. Now, I'd like to take a few minutes to focus on the healthcare provider perspective.
A recent survey of more than 430 healthcare providers around the world who had treated a patient for a mental health condition during the past year found that 79% noticed increasing patient interest in this class as a treatment option. 89% believe that this class has unique therapeutic potential compared with traditional medications, and a whopping 94% indicated their openness to integrating these treatments into their practice if approved. Now, this support is both exciting but also validates all of the work that we have done to date. As with any new treatment paradigm, there's a lot of necessary groundwork to lay the foundation for ultimate commercialization. Our engagement with the various stakeholders, healthcare practitioners, patients, clinics, and payers is already well underway. For healthcare providers and patients, preparation and education are keys to acceptance.
For clinics, site-specific education and training are critical, as are risk evaluation and mitigation strategies, or REMS, preparedness. Payers will need to see data and understand the pharmacoeconomics involved. We've been spending time with all of these stakeholders in preparation for Phase 3 to ensure we develop the necessary data sets from both a regulatory as well as a commercialization perspective. We've also been studying different models of care delivery for CYB003 if approved and how they can be streamlined for efficiency and scale to enhance patient access. This is based on both the interventional psychiatry centers that already exist today, more than 4,500 of them for esketamine alone in the U.S., as well as potential new channels that could develop between now and launch if approved. We hope to share more information about these efforts as we progress through our Phase 3 program.
There's more work to be done here, and as our clinical programs progress through Phase 3, we're working in parallel to create a commercial roadmap to ensure convenient access for patients. So let's put it all together. As an advanced clinical stage neuropsychiatry company, we continue to make solid progress. CYB003's phenomenal 12-month data, together with breakthrough therapy designation and the initiation of our Phase 3 program, make us even more excited about that progress. For our DMT program, five early studies completed with DMT and deuterated DMT have provided us with a good understanding of dosing and PK/PD relationships, so we have a solid proof of concept there, and we're now dosing in our Phase 2 CYB4 program. In addition, our pipeline product candidates address a huge unmet need in depression and anxiety, and our robust patent portfolio around these assets is among the strongest in the sector.
With cash on hand of CAD 154 million as of September 30th, 2024, we're also well capitalized to advance our programs, and as an industry, we continue to chip away at some of the stigma attached to these treatments. It's important that companies like Cybin continue to generate data and are perceived as legitimate, longer investable options with the potential to change the treatment landscape. To summarize, we're looking at important value-driving milestones across our pipeline in early 2025. We look forward to updating you on the progress of our Paradigm Phase 3 program and the initiation of the Embrace and Extend studies, as well as sharing top-line efficacy data from our Phase 2 CYB4 study in GAD in the first quarter of 2025. Thank you all again for your attention this morning, and I'll now open up the floor for questions. Operator Todd, please go ahead. Thank you.
The floor is now open for questions. If you would like to ask a question at this time, please press Star 1 on your telephone keypad. Keep in mind, you may remove yourself at any time by pressing Star 2. Again, if you would like to ask a question, please press Star 1 at this time. Our first question will come from Charles Duncan with Cantor Fitzgerald. Please go ahead.
Hey, good morning, Doug and Amir. First of all, congratulations on these very compelling data, and secondly, thanks for taking our question. The first question, though, that I had, you referred to the sample size. When you consider the types of patients that were enrolled in this study, how do you feel about being able to enroll a similar type of patient?
Are there any phenotypic, if you will, metrics that you'll be looking at to really make sure that the predictive value of these earlier data is strong for the conduct of the Phase 3 program? Thanks.
I can take that, Doug.
Morning, Charles. Thank you for the question, so you're right, and as I pointed out, the numbers are small, but when you have data that are so dramatic, even such small numbers, they tend to have a big impact, and it's like having, I give the example of adverse events. If you have something like, let's say, dizziness, you get that reported with your drug, you probably need a good 50, 100 cases to actually say that there is a signal. But if you have an allergic reaction, even one allergic reaction or one liver failure makes you stand up, and it becomes highly impactful.
I think these results are similar as in they are so dramatic that even small numbers make you stand up and take notice. Now, how do we replicate this in Phase 3? One thing is certain. Well, I think it is certain based on prior experiences that you tend to lose some of the effect when you move into Phase 3. That's natural. But when you have an effect size of two and a half, then you've got a pretty large effect, a pretty big margin. Even if you cut that down by half in your Phase 3, you're still looking at one-plus effect size, which is not what you traditionally see in the present study with the only 0.2, 0.3. The other thing we've done is not change the winning formula, as in our inclusion-exclusion criteria are exactly the same in our Phase 3.
So the population that we are looking for in Phase 3 will be exactly the same as Phase 2, and hopefully, that will help us replicate our data from Phase 2.
Very good. And with regard to the couple of meetings that you had with the agency, I mentioned those were relatively recent meetings, yes or no? And then the second question is, when you consider some of the elements, including remote raters as well as dose response for mitigating functional unblinding, what was it that the agency was most responsive to, if you could say just one, or is it the overall design?
So, response to your question one, yes, recent meetings. In terms of what the agency appreciated, at least meeting they appreciated because they agreed to our Phase 3 program, was the combination of the studies and aligning with their guidance, which they had published last year.
Our studies are exactly in line with what the FDA have recommended. We're listening to their advice and have designed a Phase 3 program accordingly.
I'll just add to that. Go ahead. Hey, Charles. I'll just add to that that I know that a lot was made about functional unblinding at the MDMA ADCOM session, but this is not a new thing for FDA. All CNS drugs have functional unblinding. If you're taking a benzodiazepine, you know. If you're taking an antipsychotic, you know. This is not new to FDA, nor a surprise. I think they've incorporated this study design into their guidance for some time now, so it wasn't really a surprise to us or to them.
Makes sense to me. Last question is regarding the capital that you have.
If no additional capital was available to the company, would the CAD 154 million that you have on hand be sufficient to at least operationalize and complete this Phase 3 program, if not just one of these studies? Thanks.
Yeah, that's correct, Charles. We expect this to be able to bring us through to top-line data readouts, exactly.
Great. Good deal. Thanks for taking the questions. Congrats.
Thank you, Charles. Thank you.
Thank you. Our next question will come from Sumant Kulkarni with Canaccord Genuity. Please go ahead.
Morning. Great to see these results, and thanks for taking our questions. I have a few here. First one, were there any changes in background treatment regimen or other variables for the patients in the 16-mg dose cohort from the 4 to 12-month time point? And did any patients feel so good that they decided to stop their background antidepressant therapy?
Yeah.
Exactly the question we are asking ourselves. But as I pointed out, Sumant, we put together a protocol amendment when we saw the remarkable results at four months, and it was an observational protocol only. So we have limited data. What we advised patients was to stay on their stable dose of antidepressant medication, and we'll, of course, collect these data in a more robust manner in Phase 3. Now, what we do know is on the 16-mg cohort, none of their patients switched their antidepressant medication. We don't know if they stopped, but we know they did not start any new medication. We had some patients in the 12-mg group, I think about four patients who switched their antidepressants, but of these, two were non-responders. One was a relapsed patient, and one was in remission.
Yeah, we've got some mixed picture there with 12 milligrams, but with 16, none of them switched to a different antidepressant medication.
Understood. You alluded to this a bit with effect sizes, but could you give us any early quantitative benchmarks for what you might consider to be clinically relevant on 6- or 12-month durability for your larger Phase 3 trials or even real-world experience-wise?
Yeah. Well, typically, a clinically relevant improvement in the MADRS is about three points. As you know, in the double-blinded portion of our study, we saw an approximately 14-point difference from placebo on the MADRS. Now, in Phase 3, with scaling this study up, more centers, likely more variability, we're likely to see that drop. The minimum acceptable would be about a 5- to 6-point difference. That's what we've powered our studies on.
And if we see that, we'll have shown statistically significant results in our Phase 3. Got it. And final one for now, it's remarkable that there were no adverse events at 12 months, but would you characterize anyone's treatment or dosing experience, to use a layperson's term, as unpleasant despite a solid response or even remission on MADRS? Not unpleasant, but intense. The experience was intense at 16 milligrams. Yeah.
Thanks.
Thank you. Our next question will come from Patrick Tuccio with H.C. Wainwright. Please go ahead.
Thanks. Good morning and congrats on the data. I have a couple of follow-up questions. The first is just, can you remind us the role of psychological support in Phase 2 and 3 trials for both CYB003 and CYB004, and how you see this role impacting clinical outcomes, discussions during potential advisory committees, and if approved, the commercialization of these compounds?
And then secondly, I appreciate these details around aspects of the design to address questions for functional unblinding. I'm wondering if you could also tell us what proportion of patients would be expected to have experience with psychedelics in these Phase 2 and 3 trials. And then lastly, just if you can tell us how you envision the Phase 3 program enrolling and whether you need data from all of these trials, the Approach, Embrace, and Extend before you could submit a New Drug Application.
Those were quite a few questions. I've already forgotten number one, Patrick. Thank you. But I can start from question two and three. In terms of limiting prior experience of psychedelics, we want the data that we generate from our Phase 3 to be generalized. And we know that patients out there are trying new therapies because clearly there is a significant unmet need.
They will be trying this class of drugs as well in an unapproved setting. What we want to do is limit that as much as possible, but keep it consistent with what is seen in the general population. So roughly about 16%-18%, that's what we know in the general population people take psychedelics.
I believe we have lost Doctor. Just one moment while I reconnect.
Patrick, maybe while we're waiting, I can answer the question about enrollment. The first study Approach has already initiated. We have 36 sites. All right. Thank you. 36 sites selected for that study, 26 of those in the US. We'll be adding an additional 40-plus sites for Embrace with very little overlap, maybe five or six sites max overlap between the two studies to maintain some independence, and so those studies aren't competing with each other.
So as you said, Approach has started. Embrace will begin as soon as practically possible after Approach, so a few months. And we expect both of those to read out in 2026. And when it comes to submission, obviously, we're still in the early days of preparing that. And obviously, with discussions with NDA, we would hope to submit a rolling submission with some of the extended long-term data available to us at that NDA submission time point. Maybe, Patrick, you can repeat the first question. Yeah. Maybe, Patrick, you can repeat the first question, and we could try and answer that one as well. Yeah. So the first one was just if you could remind us the role of psychological support in the Phase 2 and 3 trials for.
Yeah.
So well, the psychological support, firstly, I'll remind that this is not psychological psychedelic-assisted psychotherapy.
In fact, what you do see is when patients receive these drugs, they are in a state which is incompatible with any form of psychotherapy. They are in that state quite uninstructable. They do need some support, and we do give them psychological support that is largely to help them ground themselves. If they are getting anxious, for example, during the dosing session, then there is some reassurance. Of course, the clinicians are there at hand to make sure that anything that is needed from a safety point of view, they can address it immediately. What we follow in terms of psychological support is what I describe as good medical practice, which is what we will do with any medical or clinical condition.
I think we've given this example before where if you have a knee replacement, then you just don't go in cold and have a knee replacement. You have a pre-operative period where you're told what it's going to be, how long it will take, what are the side effects, what's the benefit to be expected. During the procedure, you get support, and post-procedure, you get some rehabilitation, physical therapy, and that's exactly what we do. In the pre-dose period, we will have some psychoeducational sessions where they build rapport, assess suitability for treatment, and basically tell them what to expect with treatment and teach them some strategies. In the post-dose period, it's designed to consolidate treatment gains, but no structured psychotherapy as you traditionally know it, like CBT or IPT or therapy.
In the event that this is ultimately approved, we can expect the FDA to suggest some generic requirements in terms of psychological support. It's not unprecedented. There are other classes, other psychiatric medications that the FDA have required on the label to be administered with some form of psychological support, but that is unlikely to be prescriptive in the sense it won't say what the support should be, how many sessions, how long those sessions should be, etc., but one can expect a requirement to administer these medications in conjunction with psychological support, and that's right. That's what we expect to see as well. That's what we would like to do as well.
Great. Thank you so much.
Thank you. Our next question will come from James Malloy with Alliance Global Partners. Please go ahead. Hey, guys. Good morning. Congratulations on the excellent data. Thank you for taking my questions.
I had a question. Can you walk through what the most common AEs were? I know there were no SAEs. It's excellent to see. Walk through the most common AEs. And then maybe a couple of my questions are already answered, but maybe on a bigger picture, there's been some talk with the macro events and the election of cannabis potentially being rescheduled to a three. And on a macro perspective, how do you see the bigger environment for psychedelic? Thank you.
And maybe I'll take the second one and hand it back to Amir for the AEs. Yeah. Look, Amir, I think we're in an interesting time. We've got some nominees for the in-health sector who may be a little controversial, but are certainly very enthusiastic about improving the nation's health and seem to be pro these types of treatments.
So yeah, I think we've seen for a long time that mental health and these treatments are pretty bipartisan issues. So good to see that there's not any real, there's certainly not a negative sentiment from the new administration. In fact, we might actually get some tailwinds. Amir?
Yeah. So in terms of most common adverse events, it was quite benign. We saw some headache, nausea, vomiting, and some dizziness. And we did also see some transient elevation in blood pressure and heart rate. Everything resolved on the day of dosing and once the acute effects had worn off. So nothing beyond the acute dosing period.
Great. And one quick follow-up on Peter's question as well. I think, Doug, you hit up on it. You anticipate having data for both these three Phase 3 trials in 2026, so potentially an NDA filing in 2026, early 2027? Yeah.
Ballpark, that's what we're expecting. Obviously, we're just getting things started here with the first study, and we can be more granular as we start the second study. But that sounds about right from what we're considering today, 2026 readouts, 2027 approximately for a submission from where we sit today. Great. Thank you for taking the questions. Thanks, Jim.
Thank you. Our next question will come from Robert Sassoon with Water Tower Research. Please go ahead.
Hi. Thanks for bringing excellent 12-month data. I was just wondering, I have a couple of questions. Firstly, I noticed on one of the charts, Slides you had, you had a nine-month data for the 16 milligram, and it went down to 57. So what happened there? And then it sort of bounced back to 71% remission. Yeah.
So those data kind of are representative of the disease course, as in there are typically fluctuations in symptoms over time. What we do see is that patients do bounce back. And at the 12-month time point, we see the response and remission rates going up quite significantly on any given day. When you do an assessment, when you do a rating scale, it could be affected by what happened in the morning, on your way to the clinic if you've had something in terms of transportation challenges, etc. So nothing out of the ordinary in terms of the data that we've seen, but just general fluctuations.
Okay. I was just wondering whether at that time, some people were taking, going off their meds, the traditional meds, the background meds, and there was some sort of change.
Yeah. Right. Yeah. Robert, we didn't see any patients coming off their medication.
Okay. Great. On the Phase 3, have you actually enrolled anybody yet across the sites for the first for the APPROACH study ?
We just announced this week that we've initiated. So sites have begun to be activated, and we expect screening to start imminently and enrollment shortly after that. So it's on the way.
Okay. Just one more question. I noticed that, well, you mentioned the survey, which would seem to be very encouraging for health providers because they're going to be a major factor in getting payers to cover. Plus the fact that you have Spravato, that seems to be fairly well established now and getting increasing payer coverage. So does that give you some encouragement that when you should your CYB003 get approved in '27, maybe, that you can actually get payer coverage for that from the get-go?
We've had very positive responses to our treatment profile with both clinics and with payers, and in clinics, these interventional psychiatry centers are growing in number, so that's excellent for us. I'm sure there'll be even more of them by the time we come to market, but one thing that they're running into is these clinics with a limited number of rooms, maybe it's six, eight, 10 rooms, ultimately end up running out of space because their TMS and their esketamine patients are coming back every couple of weeks, so it's hard for them to add, after a period of time, it's hard for them to add new patients, and so the concept of bringing in a patient for just two dosing sessions per year is very attractive to them, so that's a very positive, so we can leverage that infrastructure and actually help those clinics be more efficient.
On the payer side, payers are not particularly focused on the cost of antidepressants based upon our research. These patients are pretty inexpensive compared to, say, oncology patients. But they also come at some risk. So patients that progress past first, second-line treatments are then sort of on a pathway to being hospitalized or admitted potentially. And that's just something that payers will want to stop because as soon as patients progress to that level, they become very expensive and things tend to spiral. So they seem very eager and very supportive of CYB003 as a potential third-line treatment. And at the moment, we don't see any particular hurdles to coverage.
Well, that's great. Okay. Well, anyway, congratulations again on the data.
Thanks for that.
Thank you. At this time, we have no further questions in queue. This will conclude today's Cybin's Conference Call and Webcast.
Thank you for your participation. You may disconnect your line at this time and have a wonderful day.