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 open to financial analysts. 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, Wednesday, March 13, 2024, at 8:30 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, and thank you for taking the time to join our call today. We have some incredibly exciting updates to share with you today about our lead program, CYB003, our proprietary deuterated psilocybin analog in development for the adjunctive treatment of major depressive disorder or MDD. While I'll speak in more depth later about the importance of the word adjunctive here, I, I want to point out that CYB003 is the only psychedelic in development as adjunctive therapy for MDD, which is a key differentiator. Before we begin, please take a moment to note the cautionary statement language on slide two, and also on our website. This morning, we announced two very meaningful achievements. First, CYB003 received breakthrough therapy designation from the FDA.
And second, our 4-month Phase 2 durability data showed a sustained reduction in depression symptoms at the 4-month mark after just two doses of CYB003. Notably, this is the first known Breakthrough Therapy Designation by the FDA for an adjunctive psychedelic-based therapy for the treatment of MDD. Following my introductory remarks, our Chief Medical Officer, Dr. Amir Inamdar, will walk you through the outstanding data in great detail and share our vision for the path forward in light of having been granted BTD. What you'll hear from Amir about our Phase 2 durability data is truly remarkable. At 4 months, participants experienced a sustained reduction and incremental improvement in depression symptoms, with a mean reduction from baseline in the MADRS total score of approximately 22 points, compared to a mean reduction of 14 points versus placebo and 17 points from baseline at three weeks.
This is highly encouraging, especially for patients who have not responded to existing treatment options. The benefits of breakthrough therapy designation are numerous. It provides an expedited review pathway as well as increased access to FDA guidance on trial design, with the potential to significantly reduce drug development timelines. The designation acknowledges the urgent unmet medical need for more effective treatment of MDD and supports CYB003's potential for significant improvements over existing therapies. Breakthrough therapy designation serves as validation of our progress to date, and looking ahead, we can see a clear path to NDA submission. This is truly remarkable. These two milestones both reflect and drive Cybin's rapid progress and serve to advance the broader psychedelic sector.
Importantly, the durability data we are sharing today confirm our earlier findings and make us even more confident in our ability to continue the rapid pace of clinical development and to deliver more effective treatments to address what can only be described as a mental health care crisis today. Before we get into the details on CYB003, I'll first share an overview of the company and provide some context around this inflection point, including how we see Cybin leading the way forward and revolutionizing the treatment landscape for multiple mental health disorders. For those of you who may be new to the Cybin story, we are a clinical-stage biopharmaceutical company with a straightforward mission: to create safe and effective psychedelic 2.0 therapeutics to address the large unmet need for new and innovative treatment options for people who suffer from mental health conditions.
To support this goal, we have an accomplished team of drug development experts, supported by a network of world-class partners and internationally recognized scientists who share our goals. We are applying deuteration to each of our programs, optimizing pharmacokinetics without adversely affecting the underlying pharmacology, all with the goal of delivering fast onset of effects aimed at shortening time in the clinic. Intermittent dosing versus existing chronic daily treatments and convenient dosage forms, including oral and intramuscular. Importantly, rapid and sustained therapeutic effects with positive safety and efficacy. Our experienced leadership and scientific teams have a proven track record of bringing multiple drugs to market, having collectively managed 60 INDs with the FDA. Cybin has the largest intellectual property portfolio in the psychedelic drug development sector, with over 50 patents granted and more than 170 patents pending....
We have the industry's most advanced and well-protected deuterated DMT program and two proprietary advanced clinical programs in development for depression and anxiety disorders. Each now with proven and demonstrated safety and efficacy in Phase 2 studies. During the past few months, we have made enormous strides and have critical near-term value-driving catalysts across our leading programs. First, we plan to initiate a Phase 2 study of CYB004 in generalized anxiety disorder, or GAD, in the next few weeks, with a top-line data readout around the end of this year. And second, we intend to commence our Phase 3 study of CYB003 in MDD around mid-year 2024. And just to reiterate the strength of our team and the depth of our collective real-world experience, this slide illustrates the deep-rooted psychedelic, pharmaceutical, regulatory, and academic research expertise behind our programs.
The global mental health crisis, and yes, it is a crisis, and it cannot be ignored. The numbers today are nothing short of staggering. This is what drives our commitment to developing safe, effective, and patient-friendly treatment options to bring relief to those suffering. Let me share just a few chilling statistics. Almost a billion people globally suffer from a mental health disorder, with 280 million people worldwide suffering from depression. Notably, up to 30% of people with depression do not respond to traditional antidepressant treatments, and the risk of suicide is 20 times higher for an individual with depression compared to a person without. Today, SSRIs are the most common first-line pharmacologic treatment for depression, even though up to two-thirds of patients do not remit with this initial antidepressant therapies.
Additionally, antidepressants often have dose-limiting adverse effects, including weight gain, sexual dysfunction, GI disturbances, and insomnia. As you can see, with each successive line of therapy, efficacy goes down, intolerance goes up, and the chance of relapse increases. When compared with existing therapies, including SSRIs, CYB003, the turquoise column here, has shown significantly greater improvements. Note the CYB003 effect for 12 mg and 16 mg pooled after a single dose, a 14-point reduction in MADRS depression scores, compared to over 200 SSRI studies, delivering on average around just 2 points reduction versus placebo. These CYB003 efficacy and durability results also outpace other psychedelic Phase 2 results that we have seen. As I mentioned up front, CYB003 is the only psychedelic being developed as an adjunctive treatment for MDD. This is really important for several reasons.
First and foremost, patients do not have to titrate off their background medications, which is a significant benefit to them. The titration process can be both challenging and nonlinear, as some patients experience withdrawal symptoms, which can be severe after years of antidepressant use. It also eliminates logistical hurdles and the potential anxiety caused by the prospect of having to go off one's medication, even if that medication has not been previously effective on its own. And as you can see, current approved adjunctive medications for MDD offer a minimal incremental benefit when compared to the magnitude of effect seen with CYB003. The treatment pattern data show that 18% of MDD patients take multiple antidepressants, 51% take one antidepressant, and 31% don't take any at all. And keep in mind, many patients have been on antidepressants for multiple years.
If they are not getting the desired response from that medication, they might be eager to try something else. So CYB003 will target the roughly 70% of the market, with patients currently taking one or more background medications. Now is the time for a paradigm shift in mental health care, and Cybin has the scientific drug development expertise and commitment to lead the way to new, safe, and effective options. Before I turn it over to Amir, I'll just highlight the full picture of our advancing pipeline. We are proud of how quickly we've advanced the programs to date and look forward to sharing our progress in coming months. In addition to the rapid headway we're making on CYB003, I'd like to quickly touch on the advancements we're making with CYB004.
Imagine with a simple IM administration, as simple as a flu shot, we can potentially deliver a 90-minute experience with CYB004. This is quite compelling, especially when compared with other long-acting psychedelics in development for GAD. We expect to have top-line data readout for CYB004 by year-end. Today, though, our focus is on showcasing two critical milestones that we've achieved quickly and efficiently.
... I'll now turn the call over to Amir to walk you through the impressive findings and implications for our next steps. Amir?
Thank you, Doug. Good morning, everyone. Really excited to be here to provide you with an update on two pivotal milestones in our development program for CYB003. As Doug mentioned, the FDA have granted breakthrough therapy designation, or BTD, to CYB003, as an adjunctive treatment in patients with MDD. We are beyond excited about this opportunity to be able to bring this groundbreaking treatment to patients as soon as possible. Now, this BTD highlights two very important things. First, that the current treatments for MDD are suboptimal, and there is a significant unmet need for newer treatments that act faster, are more efficacious, do not need to be taken daily, are not associated with dose-limiting side effects as seen with current treatments, and provide long-lasting efficacy.
Second, it acknowledges the significance of our results and the potential for CYB003 to demonstrate an advantage over currently available treatments, thus addressing the unmet need I highlighted above. This, of course, significantly de-risks our program and provides us with distinct advantages that will allow us to fast-track the development of CYB003. It gives us access to a rolling review of the NDA with the FDA, the ability to work under FDA guidance for our clinical development plan, and ultimately be able to benefit from priority review and accelerated approval. Our P hase I/II study design has been previously communicated, but very briefly, this study was designed to evaluate safety and efficacy of CYB003 in healthy volunteers and in patients with MDD, in a double-blind, randomized, placebo-controlled design. This was conducted in participants aged 21-65 years old.
In cohorts 1-3, we assessed pharmacokinetics and safety, and we identified the dose at which strong psychedelic effects could be seen. Each participant received two administrations of the study drug. Patients with MDD that were enrolled in the study were at least moderately depressed, and we confirmed their diagnosis using the MDD screen for interview. They had to score at least 21 on the Montgomery-Åsberg Depression Rating Scale, or the MADRS, which was assessed by remote and independent rater. MDD patients we enrolled in the study were inadequate respondents, which meant that they had failed to respond to the current antidepressant treatment. But importantly, these were not treatment-resistant patients. We allowed patients in this study to remain on a stable dose of their antidepressant medication.
Now, as Doug referred to earlier, about 70% of patients are on some form of treatment or the other for MDD, and developing CYB003 as an adjunctive, therefore, addresses an unmet need for a large proportion of these MDD patients. Within each MDD cohort, after screening, which lasted for up to four weeks, participants were randomized to receive either drug or inactive placebo in a 9-3 ratio, respectively. During the study, participants were provided psychological support by facilitators who were trained in our EMBARK protocol. After being discharged from the clinical unit, on day one, after the dosing, participants came back into the clinic to receive a second dose three weeks later, where the primary efficacy of a single dose of CYB003 was assessed as an improvement in symptoms of depression using the MADRS and comparing this to the placebo patients.
All participants, including those who received a placebo at baseline, came back to receive a second dose after … a second active dose after 3 weeks, and the same protocol as for the first dose was followed for the second dose also. We conducted a second assessment for incremental efficacy 3 weeks after the second dose, so this was at day 42 or week 6. We also had an optional period of assessment of about 4 months after the second dose to help us determine the durability of treatment effects. I'll share these data with you today. On this slide, you will see that the populations enrolled across the 6 cohorts were comparable in terms of their baseline characteristics. Most of them were in their 30s and 40s.
It was fairly balanced in terms of males and females, and had an average baseline MADRS score for MDD patients, which placed them into a moderate to severe depressed category. This despite being on an antidepressant medication, which we believe is representative of a large proportion of the MDD population. We previously shared our top-line data after a single dose of CYB003, but to briefly summarize, a single dose of 12 mg of CYB003 resulted in a rapid and large reduction in symptoms of depression. At the three-week primary endpoint, CYB003 was better than placebo by about 14 points. With a highly statistically significant P-value of 0.0001. This translated into an effect size of more than 2, which you will appreciate is a very large effect size.
Similar, large, and robust effects were also seen with a single dose of 16 mg, which resulted in an improvement in symptoms of depression as measured using the MADRS total score, again, by about 13 points when you compared it to placebo. Again, these results were highly statistically significant, and the effect size was more than 2. We have also previously shared our rationale to administer two doses instead of one, and our hypothesis that a second dose of CYB003 will result in additional improvements in symptoms, and that it will ensure benefits are sustained for a long period of time, and this has now been validated.
For both the 12- and 16-mg doses, with the second administration of CYB003 at 3 weeks, not only was the initial response to a single dose sustained up to the fixed time points, but it also resulted in an incremental benefit over and above the effect seen at 3 weeks, by approximately 6 points on the MADRS total score. We also have data from facilitator debriefs. These were the people who sat with the patients in the room when they were receiving the drug. These debriefs have told us that the second dose resulted in a more intense and a more immersive experience than the first dose. And in some ways, the first dose appeared to have prepared the patients to benefit fully from a second dose. Again, validating our hypothesis of two doses. This is also evident when we measure response and remission rates.
As a reminder, a response conventionally is defined as a 50% or more improvement in symptoms, and remission is defined as a MADRS score of 10 or less. With a single dose of CYB003, about 50% of the participants responded, and about 20% of the participants went into remission. And this was not only sustained but became even better at 6 weeks. At the 6-week assessment, more than half, more than 75% of the participants responded, and almost 80% went into remission with the 12 mg dose. That is, 8 out of 10 patients were no longer depressed by 6 weeks, with just 2 administrations of CYB003, 3 weeks apart. And that's not all. It gets even better, and I'm pleased to share with you now the results from our follow-up that has recently completed.
At the 4-month follow-up, this incredible improvement in symptoms was sustained for both the 12- and 16-mg doses, as seen on this graph. On average, the reduction in MADRS scores from baseline was about 22 points in each of these dose arms, and this was after 2 doses of CYB003. Of note, no psychological support was provided during the post-study follow-up period, which is after the 6-week endpoint, and no psychotherapy was administered during any part of the study. As you will recall, patients randomized to placebo at baseline received an active second dose. These patients were also followed up to the 4-month time point. What we saw was that these placebo patients who received an active second dose also maintained their improvement in symptoms, albeit the magnitude of improvement was smaller when compared to patients receiving 2 doses of CYB003.
Again, clearly supporting our hypothesis of two doses that we included in this protocol. As you will also undoubtedly note, the lines almost look flat towards the end, which means that if you follow the trajectory, one could speculate that these improvements will persist for at least several more weeks, indicating that the durable effects lasting up to six months can reasonably be expected after, after just two doses of CYB003. This is even more remarkable when you actually look at the response and remission rates. Using the same definitions of response and remission as previously, for both the 12- and 16-mg doses, response rates continued to be maintained through to four months after the second dose, with about three-quarters or 75% of the patients still maintaining their response.
Similarly, in terms of remission, 60% of patients at 12 mg and 75% at 16 mg were in remission or no longer depressed 4 months after 2 doses. As I pointed out on the previous slide, looking at trajectories of response, it may be reasonable to speculate that this trend could be maintained at least up to 6 months. All of this in the background of a favorable safety profile. We now have safety data out to the 4-month endpoint after the 2 doses, and it still remains compelling with the relatively benign side effect profile. We did not have any serious adverse events, and all adverse events that were reported in the study were mild to moderate in intensity.
We saw no evidence of increased suicidality after treatment with CYB003, and only a few cases of nausea or vomiting, which are also observed in the placebo group. Any increases in the heart rate or blood pressure were transient, and there was no effect on EKG or any of the laboratory parameters. So in summary, and I'm sure you will agree, this is incredibly positive news for CYB003 in particular, and for patients with MDD in general. We saw rapid improvement in symptoms after just a single dose of CYB003, and the improvement in symptoms was not just rapid, but also large and clinically significant, seen as 13-14 points difference from placebo in improvement in the MADRS total scores. These results were highly statistically significant, with large effect sizes, far superior than what has been traditionally reported with antidepressant treatments.
We also validated our approach of administering 2 doses, as we saw an incremental benefit of a second dose by approximately 6 points in the MADRS, and more than 75% response and remission rates with 12 mg after 2 doses. Equally importantly, we demonstrated that these results are not transient, but durable up to 4 months, with 60% of patients at 12 mg and 75% at 16 mg still in remission without requiring any further treatment with CYB003. All of this with the background of an excellent safety and tolerability profile, with only mild to moderate adverse effects and no reports of suicidality. And to top it all, we have recently had our end of Phase 2 meeting with the FDA and have aligned ourselves on the Phase 3 program, which we intend to get going imminently.
We shall be providing more details regarding this at a later date. I am extremely excited and invigorated with this development. With positive efficacy data demonstrating durable effects up to at least four months after the second dose, breakthrough therapy designation, and alignment with the FDA on our Phase 3 plan, we are poised to deliver a life-changing treatment to people who are desperately waiting. With that, I'll pass over to Doug for some concluding remarks.
Thank you, Amir. I think you'll agree, everyone, with me that what you've heard this morning is truly outstanding. We now have a clear and compelling data that show that CYB003 to be an acute adjunctive therapy with the potential to deliver durable remission and provide a clear clinical benefit. We are finally focused and have a lot of work to do, and as we look forward to advance toward a new drug application. We expect to initiate our Phase 3 MDD trial around mid-2024, having aligned with the FDA on trial design. 15 sites, all trained and experienced in running psychedelic trials, have already been selected in the U.S., and European sites will be added. Our clinical supplies have been manufactured and are ready for the trial to commence. So why Cybin and why now?
Well, 2024 is shaping up to be a breakout year for our programs. We're just weeks away from starting our Phase 2 study of CYB004 in generalized anxiety disorder, with top-line data expected in the fourth quarter. As you've heard, we expect to begin our Phase 3 multi-site global trial of CYB003 in MDD around midyear, and we promise to share more details on the trial design in due course. We now have important clarity on the path forward for our therapeutics. The combination of breakthrough therapy designation and the compelling durability data shared today for CYB003 validate our approach and offer great promise.
I'm grateful for the support of our many stakeholders and, as always, the tireless efforts of the Cybin team members, all of whom are deeply committed to developing differentiated next-generation therapeutics with the potential to improve clinical outcomes and address key unmet needs for people with mental health conditions. I'll now open up the call for questions.
At this time, if you have a question or comment, please press star one on your telephone keypad. You may remove yourself at any time by pressing star two. Once again, if you would like to ask a question at this time, please press star one. Our first question comes from Charles Duncan with Cantor Fitzgerald. Please go ahead.
Hi, this is Elaine Kim on for Charles Duncan. Thank you for taking our questions. So the response rates were largely comparable from day 42 to 4 months, but could you help us understand the larger shift in remission rates when comparing the 12 mg and the 16 mg doses at 4 months? At day 42, it's superior with the 12 mg, and we thought it was due to better tolerability, potentially. But we're trying to understand how the 16 mg, being the higher dose, drives that increase in remission at 4 months.
Amir, do you want to say more?
I can take that. Yeah, I can take that one. So, I think first thing we need to have to bear in mind is the numbers. It's a small data set, so, you know, you can see, you know, a range of results there. Tolerability-wise, we actually did not see any significant difference between 12 and the 16 mg doses. We initially thought actually to stop at 12 mg, but, we decided to go up to 16 only because not everybody with 12 mg would respond in clinical practice, and we wanted to have an option to be able to push the dose up in some patients. And therefore, we pushed it up to 16 mg to see whether there are any issues with tolerability. And we found none. It was comparable between the 12 and the 16 mg groups.
Even though you see some differences in the remission rates between 12 and 16, they, I think, are largely due to the differences in sample size. With 12, we've got almost twice the number of patients that we have with 16. So I wouldn't worry too much about it.
Okay. As a quick follow on, will you look at both 12 mg and 16 mg in the Phase 3?
We are going to share details of our Phase 3 design at a later date. As I mentioned earlier, we have had our discussion with the FDA. We have aligned on which dose trials to move ahead with. All I can tell you now is it's one of those 2 doses.
Mm-hmm.
Yeah, I think it's okay to share that we're gonna move forward with the 16-mg dose, and that was in discussion with FDA.
Okay. Thank you for taking our questions.
Thanks, Elaine.
Thank you. Our next question comes from Sumanth Kulkarni with Canaccord Genuity. Please go ahead.
Morning. Thanks for taking my questions. I have two. The first one, if you look at the 12 mg and the 16 mg doses over time, they seem to be around the same at the farthest time point. But what do you think it means for subsequent doses? Do you think you might need to go even higher than 16 mgs on a fresh, on a fresh dose once a patient has another episode of depression?
Hi, Sumanth. Yeah, I mean, currently, the belief is no. We don't believe we will need to go beyond 16 mg if a patient requires subsequent dosing. As you know, we had two doses, one at day 21. The first dose at day 21, and the second at day 42. There is some incremental benefit of that second dose in terms of absolute change in the MADRS. That's small, about 6 points. It's, of course, twice what you see with SSRIs or SNRIs. But the real utility of that second dose is in maintaining that response. Importantly, the dose of 16 mg, or even 12 mg in patients, results in a full psychedelic experience or a peak psychedelic experience, or what you call it, a full mystical experience.
And, I know there's data that's just been published very recently as well, about the relationship between achieving a full mystical or a psychedelic experience and the therapeutic efficacy. So both of those levels, in patients, achieve a full mystical experience, a full psychedelic experience, so I don't believe we will need to go beyond 16 at all for therapeutic efficacy.
Got it. And then did you see any changes in background use of antidepressant standard of care in the patients in this trial as you progressed from week 3 to 6 to further time points? And how do you expect to ensure consistency around this variable, if it, if it matters during the Phase 3 program?
Yeah. So we, in the, 4-month follow-up, we have actually not collected those data, but we are looking at, options to get those data, and analyze whether people and how people, you know, complied with their ongoing antidepressant medication. The instruction to people was, "You, you have to stay on a stable dose of antidepressant throughout, the study." So we would expect that they stayed on very stable doses of antidepressants. In the long run, this is something that we will, watch out very carefully in our Phase 3 studies. Our Phase 3 studies will be much longer, especially the long-term follow-up will be, much longer in line with the FDA guidance. And we will include specific, you know, forms in the study where we collect usage of, data on usage of antidepressants.
It may not be unreasonable to assume that if a patient is feeling better or in remission, let's say six months down the line, they may be tempted to stop their antidepressant medication. Patients get better, they stop their medication. That's quite well known in clinical practice. But we will collect those data, and when those are available, we will share.
Thank you.
Thanks, Sumanth.
Thank you. Our next question will come from Patrick Trucchio with H.C. Wainwright. Please go ahead.
Thanks. Good morning, and congrats on this data. I have a couple of follow-up questions. The first, I'm wondering if there are any learnings to emerge from the study regarding the patients who appear more likely to respond initially and then maintain that remission over time. Secondly, I'm wondering if you can discuss more specifically the product profile you see emerging for CYB003 based on this data. I'm assuming you're able to replicate the positive results in Phase 3. And then lastly, I'm wondering if you can talk about the role of psychological support in the Phase 2 trial, and how you envision this support in the Phase 3 protocol, and how you would envision that support in a potential commercialization of CYB003 in clinical practice. Thanks.
Maybe I'll take the product profile question and hand the rest over to Amir. So I think that that's a good question. You know, as Amir mentioned, we've seen robust durability data out to four months, and those lines look pretty flat. So that you can't see any real regression back to baseline at that time point. So it's reasonable to assume that we may continue to see benefits out past six months. You know, our view is, and we've had some discussions with FDA around this, that beyond six months, they might consider another episode of depression as an acute episode, another acute episode rather than a relapse/retreatment. And that's interesting, I think, from a development perspective in terms of streamlining studies and reducing safety database.
So if we could see this as a two-dose regimen, for an episode of depression, perhaps six monthly or so, and as an adjunctive treatment, to MDD. In terms of patients that responded and not responded, I think that's quite difficult to pull that information from this study size. We'll obviously have a lot larger sample size in Phase 3. I will say that it appears that when patients respond, they really respond. I mean, the changes are quite large. So clearly, there's a group that is not responding, a very small group here, but we'll have more info on that, I think, in Phase 3. And maybe, Amir, you want to comment on psychological support?
Yeah. Yeah, and very quickly on responders, as Doug said, the characteristics—the only feature in people who respond is that they have a pretty intense experience and a pretty immersive experience, which we kind of ensure by giving a second dose. First dose acting as a prep for the patient for the experience, and the second dose, they are able to fully experience the immersive nature of the psychedelic effects. And you see that in you know, incremental benefits over time. But going back to the question about psychological support, we used the standard clinical framework, which is basically when people enrolled into this study before they received any medication.
In the 3-dose period, they were provided with psychological support, which largely consisted of psychoeducation about what to expect from the treatment and the sort of rapport building with the patients, which is not unlike any other treatment. Most of it we did remotely. We've utilized telemedicine quite a bit in this study to deliver the psychological support element. The only time there is an actual requirement for the monitors or facilitators providing psychological support to be in the... It would be patient is during the dosing session, and that's largely handholding, reassuring, nothing else. And then post-treatment, again, in the post-dose period, they get provided with debriefing sessions. We expect to use the same approach in Phase 3 program.
What we've done though is, we've made that psychological support program, which is called EMBARK, and developed in-house. We've streamlined that a bit more into a program called EMBARK-CT or EMBARK for clinical trials, which basically is aimed towards scaling, helping scale that psychological support to large Phase 3 clinical trials, which will be hundreds of patients. So fundamentally, nothing changes in the psychological support program except that we've streamlined it for our later phase studies.
Terrific. That's very helpful. Thank you, and congrats again.
Thanks, Patrick.
Thanks, Patrick.
Thank you. Once again, if you have a question or comment at this time, please press star one. We'll go next to Jim Malloy with Alliance Global Partners.
Hi, guys. This is Matt Venezia on for Jim Malloy. First of all, congrats on the data readout, and thanks for taking the questions. My first question was, are you guys planning at all to include patients, that 30% of patients of MDD who are not on an SSRI? I know in the last R&D day, you had talked about only patients that are already on an SSRI for the Phase 3, but will you be including that 30% at all down the road, as like a monotherapy?
... Yeah. Right now, the indication is for adjunctive. We are only designing studies with CYB003 as an adjunctive to ongoing antidepressants, SSRI or SNRI. Maybe once we've completed this adjunctive program, there may be an opportunity to explore CYB003 as monotherapy as well. But the current indication in the plan is as an adjunctive to SSRIs or antidepressants.
Yeah, I'll add to that. You know, that, clearly, this is unlikely, we think, in the current sort of, environment for de novo patients that are not on any background treatment, just to jump straight to, you know, a psychedelic treatment. It's more likely that they'll go through their primary care physician, receive, you know, a few tries of SSRIs or SNRIs before making it to a specialist, and that's, you know, where we see these treatments being positioned. So it might be interesting to study patients on no background medication, but it seems that in the real world, that's an unlikely scenario.
Got it. So just to follow up, you, you guys mainly see, the psychedelics, being prescribed by specialists exclusively?
Yes.
Okay. Got it. And then I just wanted to ask a little bit about the Small Pharma assets and how the clinical development for those is going currently.
Yeah, sure. Thanks, thanks for asking that question. So we're very excited about this, these CYB003 results, but also we're excited about CYB004. You know, what we achieved with the Small Pharma combination, which has gone very smoothly and very efficiently. We've combined our various data sets, a total of 5 trials now, around deuterated DMT. A lot of Phase 1 PK/PD data that really helps us understand the dosing dynamics of DMT and deuterated DMT. And of course, we also have Phase 2 results from non-deuterated DMT in depression, and the impact on anxiety scores. So we have a terrific proof of concept.
and between psilocybin and Small Pharma, the work was all adjacent, not overlapping, and has enabled us to jump right into a Phase 2 study with CYB004, and move from an intravenous infusion to a simple intramuscular injection, just like a flu shot. And that was possible because of the combination of the datasets and, of course, importantly, the combination of all of the collective IP between the two companies. So we are focused on CYB004 now and moving into Phase 2. That IND has been cleared by FDA for an intramuscular study, and we're just a few weeks away here from kicking that off.
All right. Thanks again for taking the questions, and congrats once again.
Thank you, Matt.
Thank you. Our next question will come from Francois Brisebois with Oppenheimer. Please go ahead.
Hi, can you guys hear me okay?
Hey, Frank.
Yep.
Good morning.
Yep. Hi. Sorry, I've been having issues with the star one button. Thanks for taking the question. So just, how do you guys... Just can you touch on the commercial potential here and just thoughts around duration? It seems like, you know, the angle has been to do maybe a shorter duration treatment, even with CYB003. Now it seems like repeat doses is probably the angle you're taking. I'm just trying to understand, you know, if CYB004 is a 90-minute kind of procedure, how does CYB003 look in terms of duration? And any thoughts about the scalability aspect of the commercial side for a shorter duration here versus a longer duration? Thank you.
Yeah. I think duration is important, but so is the protocol and the redosing timeline and schedule. You know, it's encouraging now to see Spravato doing very well. I think it's change, it's fastest growing product at this point. And that's with a treatment that requires patients to go to a clinic for treatment 8 times in the first 4 weeks, and then multiple times thereafter. So 8 visits to the clinic. They have to be driven back by a third party because they can't drive afterwards. Not meant to drive for the rest of the day. So basically, those days are shot for those patients. So 8 of those visits in 4 weeks.
We see here, with both CYB003 and CYB004, much reduced overall timelines and a dosing schedule, at least for CYB003 here, that might be two visits at a minimum, every six months or maybe longer. So a far less onerous and burdensome schedule and protocol for the patient. As we've said before, with CYB003, we see a very rapid onset of effects, you know, because of the pharmacokinetics that we've modified. Effects begin in about 15 minutes, and the peak PK is at about 1 hour. The peak psychedelic effects last about two hours. So that's really the therapeutic window, that two-hour point. And then patients come down into the sort of tail of the PK curve, if you like, and then a bit of an afterglow.
So on average, we allowed the patients to sit as long as they wanted in the Phase 2 trial. And the facilitator used their judgment on when the patients were ready to go. But on average, the sessions lasted 4-6 hours, something like that. So a little shorter than you might expect with traditional psilocybin, which is around 6-8 hours, and certainly a lot shorter than you might see with other long-acting psychedelics like LSD.
... Have you guys done work on kind of the health economics to these clinics and the centers and the benefits of a shorter acting or more patients in the chairs? Any work there on the commercial front yet?
Yeah, we have done some initial work, and, but our initial view was that once you start to see durability beyond about eight weeks or so, so fairly short, economically, this starts to look very interesting for, for payers. And of course, now we have durability data out to, to four months or so. We're continuing to do work with payers and doing some primary research, and we will share some of those thoughts another day.
Thanks.
Thanks, Frank. Thank you. We do have a follow-up question from Sumanth Kulkarni with Canaccord Genuity. Please go ahead.
Thanks so much for taking the follow-up questions. A couple. First, as an organization, from a commercial point of view, what do you think a sweet spot is for durability of your treatment? And second, when do you expect to have meeting minutes for the end of Phase 2 meeting from the FDA in hand? And in broad strokes, can you give us any details on what the FDA was most focused on during that meeting?
Our goal has always been from the outset to maximize durability. That's why we went with the two-dose regimen in the study. Where we hypothesized that with the more intense second experience, the efficacy results would be sustained for longer. And you know, in our own hypothesis and the discussions with FDA, you know, we are trying to aim for a point of at least six months before retreatment. Also, aiming for a label that is acute treatment of a depressive episode of MDD, rather than having to establish a sort of more personalized redosing schedule. Of course, when you have a more acute label, then the safety required database requirements are reduced as well.
So that's part of our ongoing thinking as we look to repeat some of this data in Phase 3. And then in terms of FDA discussion, I can say that it was a very collaborative meeting. We had more than 20 or so folks from FDA participate. There seems to be a very wide interest across all departments at FDA in these treatments and learning about them. Very collaborative discussion. Minor tweaks to our Phase 3 proposal that are no surprises. I'll just say, you know, we have a clear path to Phase 3, and no hurdles now, we believe, to beginning our first study around midyear.
That's very helpful. Thanks, Dan.
Thanks.
Thank you. At this time, I would like to turn the call back to Mr. Drysdale for any additional or closing remarks.
Yeah, thank you, Todd. So that concludes our call today. Thank you all for your interest in Cybin and for joining the call. And we look forward to doing this all again for CYB004 in a matter of months. So, thanks very much for joining. Have a great day.
This does conclude Cybin's conference call and webcast. You may disconnect your line at this time, and have a wonderful day.