Cybin Inc. (HELP) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and thank you for standing by. Welcome to Cybin's conference call. [Operator Instructions]. I would also like to remind everyone that this conference call is being recorded today, Wednesday, November 1, 2023 at 11:00 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, operator. Good morning, everyone, and welcome to our call today. I'm joined today by our Chief Medical Officer, Dr. Amir Inamdar. Yes. We appreciate this opportunity. This exciting opportunity to share with you some truly compelling data from our Phase II study of CYB003 being developed to treat major depressive disorder, or MDD. We'll get into the details in just a moment. But first, I'd like to reflect on the significance of this progress not only for Cybin, but for the whole psychedelic sector. This is truly a transformational time. And with the unprecedented positive data we'll share today, we grew more confident in our ability to develop and deliver more effective treatments to address the mental health care crisis we face today. For those new to the Cybin's 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 a talented 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 also there were other flags aimed at short end clinic times, intermittent dosing versus existing chronic daily treatment, convenient dosage forms, oral subcutaneous intramuscular. And importantly, rapid and sustained therapeutic effects with positive safety and tolerability. Our experienced management team has a proven track record of bringing multiple drugs to market, having collectively managed 60 INDs in the FDA. We have the largest IP portfolio in the psychodelic drug development sector with over 33 patents granted and more than 170 patents pending. We have the industry's most advanced and well protected generated DMT program and 2 proprietary advanced clinical programs in development for depression and anxiety disorders. Each now we've proven and demonstrated safety and efficacy. Over the course of the next few months, we foresee a number of near-term value-driving catalysts across our leading clinical programs. Including for CYB003 Phase II top line efficacy data expected by the end of the year. For CYB004 and SPL028 Phase I top line safety, dosing, PK/PD data also by year-end. And we plan to have 4 clinical trials upcoming in 2024. Including a planned global Phase III trial of CYB003 in NDD and a Phase II proof-of-concept study of CYB004 in generalized anxiety disorder each beginning in early 2024. Additionally, we'll be running 2 formulation studies a subcutaneous study for CYB004 and an intramuscular formulation study with SPL028, each with the goal of creating more convenience and less invasive dosage forms for patients. To understand why we're so passionate about all of this you just have to look at the staggering statistics around mental health conditions. To share just a few, almost 1 billion people globally suffer from a mental health disorder with 280 million people worldwide suffering from depression. Up to 30% of people with depression do not respond to traditional and depressant treatments. And suicide risk is 20x higher for an individual with depression versus a person without. And while SSRIs are the most common first-line [ pharmacy ] treatment for depression, up to 2/3 of patients do not remit with initial antidepression therapies and antidepressants often have dose-limiting adverse effects, including weight gain, sexual dysfunction and insomnia. We aim to change all that by adding a new, safe and effective opting. Before we get into the CYB003 results, I'd like to remind you all of our extensive DMT program, which includes impressive efficacy data in MDD from SPL026. In a Phase IIa MDD study, SPL026 delivered rapid onset of effects with a 7.4 point reduction in matter score at the 2-week primary endpoint. To put that into context, that's approximately 4x what is typically seen from SSRI therapy. And impressively, 40% of MDD patients were deemed to be in remission at 6 months following 1 or 2 doses of SPL026, providing tremendous proof of concept for our derated DMT program. And when added to SSRI therapy, SPL026 was well tolerated. And with 92% of the SSRI group in remission at 4 weeks after a single dose. Just remarkable. These data sets are clearly impressive, and they go a long way in derisking our deuterated DMT program. Today, we're showcasing the unprecedented positive Phase II interim data for CYB003, with a focus on Cohorts 4 and 5, which each received a single dose of 12 milligrams of CYB003 or matching placebo. The purpose of this Phase II clinical trial was to evaluate safety and also efficacy using the MADRS scale on the Montgomery-Asberg Depression Rating Scale. And the primary efficacy endpoint was a reduction in depression symptoms and change from baseline in MADRS at week 3, after a single administration of CYB003 versus placebo. I'm thrilled to share that we observed a rapid, robust and statistically significant reduction in depression systems. 3 weeks following a single 12-milligram dose of CYB003 compared to placebo. Remarkably, 53.3% of patients responded and 20% of patients were at the remission. Meaning, they no longer met the clinical definition of depression. This compares to the 0% for placebo for each of these measures. These overwhelmingly positive interim results hold enormous promise for improving patient outcomes and quality of life. I'll now hand the call over to Amir to walk you through the data.

Thank you, Doug, and good morning, everyone. If you could move to the next slide. This is basically an overview of the clinical trial design for those of you, who haven't seen this before. The study was a randomized double-blind design. It was conducted in adult patients with major depressive disorder. These were aged 25 to 65 years old. And it was an ascending dose cohort design. So the NDD patients we enrolled in the study were at least moderately depressed and we included patients, who were inadequate responders to their ongoing treatment. Importantly, we allowed all patients to remain on their ongoing anti-depressant medication. So this was an add-on treat. The intent for Cohorts 1 to 3 was basically to assess pharmacokinetics and safety and identify those at which strong psychedelic effects could be seen. These were, therefore, smaller cohorts with 4 participants each. And 2 doses were administered in each of these Cohorts. Cohort 1 was MDD patients, but we soon realized after Cohort 1 that we needed to pivot to healthy volunteers for cohorts 2 and 3. Firstly, to speed up recruitment. And secondly, because we knew that at the lower doses, there would not be any therapeutic benefit. The way cohorts were designed was that after screening, participants were randomized to the feeling either active drug, CYB003 or placebo in a 9:3 ratio, respectively. Once randomized at the dosing session, participants were administered the study drug. And during this session, they were supported by facilitators, who were trained in our EMBARK protocol. At the 3-week primary efficacy endpoint, we assessed the effect of a single dose of CYB003 by comparing a single dose of active versus placebo. We chose the regimen of 2 administrations 3-week support as we believe that will give us the best chance of demonstrating robust and durable efficacy. Therefore, in this study, all participants receive an active second dose after 3 weeks. At the 6-week time point of the assessment of efficacy, where we are able to evaluate the incremental benefit of a second dose in those patients, who received an active treatment on day 1. We also have an optional period of assessment that will help determine the durability of treatment, and this is out to 12 weeks. On the next few slides, you will see efficacy data for Cohorts 4 and 5 at 12 milligram, which we're showing you today. While we started seeing psychedelic effects at 3 milligrams, and robust effects that were consistent with therapeutic efficacy, we already started seeing those at 8 milligrams. The onset of psychedelic effects was rapid with noticeable effects being observed and reported at 15 minutes post oral dose, maximal or peak effects were seen in 90 minutes and these lasts for about 2 hours. With majority of the participants reporting the maximum score on the visual analog scale, which is 100. So next, please. We enrolled 24 participants with major depressive disorder across the 2 cohorts. The cohorts were fairly balanced in terms of age and gender. 18 were randomized to an active first dose and 6 to an active -- 6 to the placebo. As you can see, we had comparable baseline matters scores, which was just about in the severe category due to the fact that we administered 2 doses to each participant, we are eventually going to get about 78 exposures by the end of Cohort 6 even though we enroll only 48 participants. And the table on the right shows you how many were enrolled and exposed in each cohort. On the next slide, you will see the results that Doug referred to earlier. A single dose of CYB003 resulted in rapid and robust improvement in symptoms of depression. This change in symptoms of depression was assessed using the MADRS total score in change from baseline. The downward direction of the lines indicate improvement, placebo being represented by the black line and CYB003 being represented by the pink colored line. The vertical lines of whiskers represent standard deviation, which is the representative of the sample size. As you can see, a single dose resulted in a rapid and large reduction in symptoms of depression at the 3-week primary endpoints, CYB003 was better than placebo by 14 points, with a p-value of 0.0005. This translated into an effect size of 2.15, which you will appreciate is very large. And actually, maximum improvement was already evident as early as 10 days after dosing and was sustained up to the 3-week time point. On the next slide are the response and remission rates. Typically, when you assess a response with conventional treatments like SSRIs, you assess those in about 4 to 6 weeks. But what you can see with CYB003 is that with a single dose, more than 50% of the participants responded, which means a 50% reduction in the MADRS score. So if they started at 30, 33, it's almost a 15-point reduction. And within 3 weeks, 20% of the participants went into remission. Remission was defined as single-digit MADRS score. So score is less than 10. That's incredible when you put that into context of how long it takes with conventional treatments to see any sort of response in symptoms of depression. On the next slide, you can see that this is all with a very favorable safety profile. CYB003 was very well tolerated. We didn't see any serious adverse events. We did not see any events of suicidality either. The most common side effects were nausea, increased in blood pressure, which was transient and headache. These are all as expected. Nothing was out of the ordinary. So to summarize on the next slide, a single dose of CYB003 resulted in rapid and large improvements in symptoms of depression. These improvements were highly statistically significant at week 3 and fast superior in magnitude to what is typically seen with other antidepressants, meaning we have a large effect size as 2.15, in contrast with the SSRIs, which are the standard of care, effect size are traditionally very small investments. This excellent efficacy is accompanied by an excellent safety profile as well, which has allowed us to progress into the higher dose cohort of 16 milligrams paving the way for our Phase III study in Q1 2024. With that, I'm going to hand back to Doug. Thank you.

Thank you, Amir. So as you just heard, there's an awful lot to be excited about here and a lot to be hopeful for. To put these results into context, let's take a look at the treatment landscape. I'm sharing here a range of data. Providing a cross trial analysis purely for context and illustrative purposes, not meant to be a direct ahead comparison. However, if we look at 232 clinical studies of SSRIs, since 1979, we see a mean reduction in depression score of less than 2 points versus placebo. If we look at the more modern antidepressants approved over the last decade or so, we certainly see improvements over SSRIs. And we're showing here on this chart the best score improvements from pivotal studies of these treatments. But still about twice the mean change seen with SSRIs. Then we look at the results of psychedelic studies, and we see a 6.6 point improvement in a Phase IIb study in TRD patients from COMP360. And impressively, a 7.4 point improvement in MADRS score versus placebo from SPL026 in MDD patients. It's easy to see why there is so much excitement for the potential therapeutic benefits of psychodelic molecules, when you look at these studies. So with that context, these interim results from CYB003 a 14-point reduction in depression symptoms compared to placebo are truly remarkable. And let's not forget that both groups in our study, including the placebo group, while also receiving SSRI treatment, meaning that the benefits of CYB003 are on top of those from SSRIs. And patients don't have to go through the challenging process of titrating off existing treatments. With these interim results showing a significant improvement in the depressing symptoms with a single dose, we're moving ever closer to delivering on our mission to improve the treatment landscape across the spectrum of mental health disorders. CYB003 is now close to being a Phase III-ready asset. And we're highly focused on the next steps along the regulatory pathway. Plans ahead include submission of top-line data this year to the FDA and requesting an end of Phase II meeting of the FDA to be held in early 2024. The goal there will be to align on the Phase III trial design and we're commencing dosing of a capsule formulation of CYB003 right now in a bioequivalence cohort and further manufacturing GMP materials that will be dose flexible, patient-friendly and commercially scalable and ready for recruitment of Phase III patients around the end of quarter 1. We also intend to initiate a U.S. Phase II study in generalized anxiety disorder for our generating DMT program and with 2 formulation studies planned in parallel, a subcutaneous formulation of CYB004 and an intramuscular formulation of SPL028, with the aim of creating less invasive and more convenient dosage forms for patients and for providers. So as you can see, there's quite a long list of potential value drivers ahead of us over the next few months. And with that, operator, I'll open the floor for questions, please.

[Operator Instructions] Our first question comes from Charles Duncan with Cantor Fitzgerald.

First of all, congrats on the interim results and also recent progress and thank you for taking our question. I had a couple on CYB003. Just -- I wondered if you could provide more color on the experience base of these patients? Did they have experience with psilocybin in the past? And you mentioned that they remain on current treatment I'm wondering if there was, call it, an interaction with background therapy in terms of the effect sizes that you're seeing, maybe a little bit too small of a cohort to be able to say, but what's your perspective on that?

Being represented by the pink colored line. The vertical lines of whiskers represent standard deviation, which is the representative of the sample size. As you can see a single dose.

Sure. Amir, do you want to take this one?

Yes. So your first question, Charles, and thank you for those questions. We excluded experienced patients. So basically, what that meant was we restricted the number of times people may have taken a psychedelic in the past for whatever reason. It was pretty strict over 10 years, I believe, we allowed only once or twice. So the intention was we wanted to exclude habitual or frequent users of psychedelics. So it -- in other words, a relatively psychedelic naive population. The other question, I think, was about background SSRIs, background anti-depressant treatment. And yes, where these patients were allowed to remain on their anti-depressant treatments, which actually putting that into context with the results it probably makes the results more impressive because it's always more difficult to show an incremental benefit over an existing therapy. The state on the therapy, they probably also benefited from taking the anti-depressants. They're ongoing anti-depressant. But importantly, that happened in the placebo group as well. So any advantage due to taking an anti-depressant would have been negated by -- in the placebo group, if that makes sense.

Yes. It does. Really, what I'm asking is whether or not background SSRI or SNRI therapy impacted the effects size like in patients, who were less experienced may have had a higher impact. And then regarding the experienced patients. I guess I'm wondering, could you address the concept of functional unblinding, any concern about that in terms of misguiding on the results.

Yes. So first, the background treatment question. We didn't really anticipate any interaction in the sense of a pharmacodynamic or pharmacokinetic interaction. I know in the past, there have been concerns around SSRIs blunting the effects of psychedelics. We did not see anything to that effect at all. From methodological point of view -- from a mechanistic point of view that wasn't something we were concerned about. On the other hand, we realized it would be really challenging to take people off their ongoing antidepressant treatment that would create a burden not just in a hurdle, not just in the clinical trial, but also eventually, when this is rolled out. So we made that call to allow people to stay on their anti-depressants. This is also in the background of some information coming out around SSRIs, making the experience more tolerable. In fact, if you look at some of the GMT data that Doug shared earlier, those people, who remain on SSRI and received DMT. And I know it's not apples-to-apples, but it's the same category, psychedelics. They did really, really well. Going back to your question of functional unblinding, yes, it's an interesting one because there really is no good comparator or active comparator for a psychodelic. The effects are very obvious. However, it's interesting how difficult it is to tell, which patient is on which drug active or placebo, when the results are blinded. We try to guess in all honesty, and we got it wrong. When you look at the visual analog scale scores -- when you see scores around 6, 7, you're thinking out of 10, you think including this patient probably is on an active drug. And we try to do that. It's difficult not to do it when you see the data come in. But once the analysis was done, we found out how wrong we were. And even patients, who were on placebo when they receive the drug in a blinded manner, they had some effects mimicking psychodelic effect. So yes, there's a risk of functional unblinding, but it seems that placebo really did its job as a comparator.

If I could ask one question in terms of forward looking, if you will, in terms of next study. I guess I'm wondering either for you, Amir or Doug, when you think about the target product profile of CYB003, it seems to me that you could have less heterogeneity in terms of absorption, maybe? And I guess I'm wondering if you believe that could drive a relatively capital-efficient Phase IIb or Phase III study in terms of perhaps peer patients needed to find the effect size. And then thinking about this 12-milligram effect size pretty notable versus one that you may see with 16 milligram. I guess what -- if you had to guess what your go-forward dose would be, do you have a favor?

Maybe I'll take those, Charles. Look, I mean, it's very clear from this data that 12 milligrams is an effective dose. Our goal with 16 milligrams, let's to see if we could get a few more patients across the line as with any improvement, not everyone responds. While also trying to make sure we keep the side effect profile in check. So we'll take a call on that, since we see the full top-line data, when we look at the queue sets of data side-by-side but efficacy and safety profile. To answer your question about Phase III design, yes, I think we can assume a fairly efficient Phase III study, very similar to the Phase II design in that we'll be providing 2 doses of CYB003, 3 weeks apart. But no crossover in this, at least could dispose that those doses compared to a pure placebo. And that study at the moment, obviously, we will have to convene on a little bit with FDA on the basis of any Phase II meeting. But I still, at the moment, we have intended to be around 220 patients. Sorry a decent size, but not massive, and so manageable, should be relatively efficient. Randomized 1 to 1. So that study, current draft design has an 80% power to share of 5. Even though we are -- we are seeing a 14-point improvement here, we're being obviously conservative in our Phase III design. So that study at the moment is going through a peer review. And we'll put that final draft in front of the FDA in quarter 1 and then share.

And can I clarify on -- you mentioned placebo, but these are patients not on placebo. They're on supposedly active background. So your Phase III would be against placebo or against whatever background therapy session was that?

Yes. Thanks for the question and the clarification. So the population is anticipated to be the same. So moderate to severe patients with MDD that are also taking an SSRI or SNRI. So you're right, both groups to be in the placebo group will be on background therapy, which we believe are a representative of the real world.

Next question comes from Patrick Trucchio with H.C. Wainright.

This is Luis for Patrick. How does CYB003 differ from other first-generation psychedelics. So is there any particular beneficial attribute that is coming from the specific generation relative to the older compounds? Is there anything on the mechanistic side that you can speak to?

Yes. So we've been careful here, and thanks for the question, Luis. We've been temporarily not to modify the active parts of the compound. We didn't want to change receptor binding profile. We don't want to impact efficacy necessarily adversely or side effect profile obviously. So the modifications that we've made have been designed to optimize the pharmacokinetics. What we were seeing, and we're doing that through deuteration, substitution of hydrogen atoms on the molecule we get in a very specific way. Preclinically, we saw an increase in brain-to-plasma ratio. So higher concentrations in the brain compared to the plasma, when compared to psilocybin. So when we compare the two, we saw about a 40% increase in brain-to-plasma ratio with CYB003 compared to brain-to-plasma with Cybin. And an increase in bioavailability. So it does appear that maybe those characteristics, the changes in PK are driving an increase in potency. And as Amir said, we've seen really robust psychedelic effects at doses as low as 8 milligrams. So compared to, say, a typical dose of the psilocybin, which might be 25 milligrams. So although we haven't done that direct head-to-head in terms of efficacy or potency, it's clear we're seeing effects of normal doses. And the same is true also with DMT and the benefits of the DMT is now we're able to put the dose into a very small volume. Maybe a subcutaneous or injection into muscular injection and remove the need for expensive and technical equipment driving infusion pump, which your psychiatrist, and psychologist, therapies just don't have in your offices. So the degration is helping it seems to be helping the potency here, and it's going to be helping with multiple dose forms with DMT.

And the follow-up on that. How should we think about the relapse remission rates that were generated in the Phase II trial with compared to other compounds that are approved or are in development as adjunctive treatment. So since you are using this on top of background therapies, I assume that other compounds on top of SSRIs will also have -- or potentially might also have an incremental effect. So the -- how should we think about this relapse in remission rates?

Yes. So I think it's clear, when you look at historical development in depression, it's really quite difficult to show incremental benefits on top of existing treatments and most drugs approved monotherapies for that reason. I think that, and last one, I would called that was to benefit as an incremental -- incremental treatments and adjunctive treatments for SSRIs for MDD was perhaps identified or [indiscernible]. I believe peak sales of that product or around $6 billion or $7 billion annually. So there's a massive unmet need for patients that are not getting all the benefits they would need or like from their SSRIs. And we know that SSRIs don't work for everyone. They do like for some people, don't work every one. And often, people have breakthrough depressive episodes, when they're still on the SSRIs. So having another option on top of their SSRIs. And to get a 53% response rate that are inventive therapies is pretty remarkable.

One last question. On the DMT program and your expectations in generalized anxiety disorder. How should we think about the design for that program and the goals of the Phase II trial. So we'll outland the Phase II design in the short time, once we had that locked down. It will be compared to placebo people concept study. If remember that GAD patients have a lot of similarity to MDD patients. There's about an 80% overlap in symptomology and diagnostic criteria. So I would say that given we know that SPL026 is efficacious in MDD. The DMT is efficacious in MDD. Then there's a high probability we believe in showing efficacy in this group that GAD patients that have depression. And of course, when you look at anxiety disorders overall, they affect about 18% of the U.S. population. So it's really a very large group of folks, where current treatments are really not very satisfactory.

The next question comes from Francois Brisebois with Oppenheimer.

Just -- so firstly, I was just wondering if you could comment about your placebo arm. One in the remission and relapse, there is a 0%. And then also just in terms of the chart in terms of maybe the lack of variability or the very positive for your trial looking placebo arm. Is there anything that you did here? Or do you think keeping them on SSRIs might help explain it? Or is it just a small end number, and it's very hard to say why the placebo had quite a bit less variability, I guess?

Yes. Amir, do you want to take this one?

Yes. Yes. No, actually, with the response and remission rates, that's really unbelievable isn't it? I guess that's why you're asking the question. So high at 3 weeks, 53% responders and 20% remitters, and we just didn't see anything at all in the placebo arm. I don't know -- I don't think it's that's due to small numbers because it's small numbers, you should actually have more variability. It's simply that people realize that they are not on the drug. And as we say, a background of either an SSRI or SNRI is making sure that there is no significant fluctuation in their symptoms and they kind of plateau out.

Okay. And if you were to pick like which is more impressive to the responder of 50% or greater in the treatment arm or the 0% in the placebo arm.

I'll clearly, responders, I would say. At 3 weeks, 50%-plus responders is quite remarkable. We don't really see that with the conventional treatments, it takes at least about 6 weeks to even assess -- 4 to 6 weeks to start seeing some effects. And responders is like a 50% reduction in symptoms, that's quite remarkable.

To answer that -- just to answer that, frank. Is that, recall, we although we were recruiting patients with MADRS scores about 20. So moderate to severe. We ended up with a baseline in each of the active placebo groups of around 33, so in a more severe end of the spectrum. So to still see this remission rate with that baseline starting point is pretty remarkable.

Understood. And then maybe can you just discuss a little bit the -- you talked about the end number. Were there any dropouts here? Or anything to note?

Yes. Yes, yes. On the -- between the 2 courts, we actually enrolled 24 patients. So that was 18 on active and 6 on placebo, but we had 3 dropouts from the active group. The dropouts were not due to any safety or tolerability issues. They were purely for logistic reasons, scheduling issues. And we decided to exclude those patients from our analysis. So when you see the numbers there on CYB003, we had 15 completers for protocol completed and on placebo, it was 6. So in total, 21 participants.

Okay. Great. And then maybe lastly, do you discuss anything about the duration of the treatment? Is this as long -- was this as long as regular psilocybin? Or does the de duration help reduce the time of therapy?

We're certainly seeing a fast onset. So as we've reported before, onset of effect in about 15 minutes. So that doesn't mean the patient is not waiting around and potentially having a bit of anxiety or even more. So they're just taking something that's quite powerful. So that passed on something is very good for patients. The peak effects last about 2 hours. So the peak therapeutic time is about 2 hours. So relatively short. And then the patients start to calm down as starts to recover. We haven't strictly measured the time from beginning to end because generally, you're trying not to disturb the patients. During the [indiscernible] session. But we believe that from -- based on antidoted feedback from the facilitators that in the 4 to 4.5 hours range end-to-end, beginning-to-end. So substantially shorter than some of the anecdotal time you've heard regarding in sort of Cybin sessions, which could be [ $600 ] I believe.

Okay. If I could just sneak in a last one here. Would you -- in terms of Phase III, you talked about 220, one-to-one could there be multiple Phase IIIs? And would you ever look at -- I know you said it'd be similar patients here on SSRI to a previous question, but would you ever look at weaning off patients of SSRIs or just going after a true placebo or just to see if we can totally get rid of SSRIs.

Yes. So currently, we're sticking new patients that are taking the SSRI. We think that's a lower hurdle for patients and a lower hurdle for practitioners. Titration is difficult. It's quite challenging. The dose titration down is not linear. Many patients often going too far and have to take a step back. And then the reported rebound effects from titration coming off of these SSRIs made us up to a year. And those rebound effects may compound the study drug at some point. So for now, we're sticking with the positioning CYB003 as an adjunctive therapy. And in terms of Phase III, I think the FDA has made it fairly clear they are in the draft guidelines that they would like to see both a pure placebo as we use in the Phase II study and as we are planning for our first Phase III. And they also want to see a low dose or medium dose or some kind of dose range in as well to perhaps move some of them don't the effects and they tend to look at the complete data set from 2 Phase III study.

The next question comes from Sumant Kulkarni with Canaccord.

I have 3. So first, did the compliance rate of background SSRI or SNRI has been either the placebo or the active group change over the 3-week period in this Phase II study. And going forward, how do you -- how would you ensure that does not change?

That's one for you, Amir.

Yes. So we're still to dig into those data, Sumant? That will be out when we share the top line data in November, early December. But from reports from these, we have no reports on this site that compliance was poor, if you like, in a clinical trial setting, as you can imagine, everything that goes into the patient's mouth is recorded. So we will have all those details with whether -- which drug it was, how long, which dose, et cetera. And we can share that with you once those data are available. Compliance is tricky even in clinical practice, you ask people to take a drug and people are lousy with taking their medication some time. And often it's very, very difficult to make sure they take medications, same medication at the same time every day. And I think that's one of the beauties of having a treatment, which only needs to be given once or twice in the clinic as with CYB003. So you don't really have to worry about compliance. When they go back home, take their SSRIs, you do expect some reduction or some level of poor compliance. In a clinical trial setting in a shorter clinical trial, I would expect it to be less than the typical 80%. But it remains to be seen. Again, we will collect those data in the report out on those as and when we have them.

Got it. And then my second question, now that you have these interim data in hand, could you share any hypothesis you might have on the durability of effect of 1 or 2 doses of over 3 weeks apart that we wait for this fullest Phase II data set yet.

Yes, we will see. We will see. We would say to try to design a treatment and a treatment protocol that is designed to do just what you are asking Sumant, that is to extend the durability of effect. I mean ultimately, that's the goal I think it's fairly clear now that these psychedelic molecules have efficacy, but durability is equally important, and that's why we're taking the time to modify the PK, the potency. We have pushed the dose ranging up to 16 milligram. And we're also, as you say, are applying a second dose 3 weeks after the first dose. I would hope to expect that we might see an increase in response or remission rates for the second dose. We have some patients just don't get across the line in the first time with psilocybin. It's a bit of a wavy experience, it's a very technical term. And some patients resists or are pitiful or anxious and then maybe get the full benefits the first time around. So we will see when we analyze the data, the difference between one dose and two dose and the impact of that on durability. And we'll have that towards the end of the year?

Got it. And then my last question is a financial one. So what are your latest thoughts on your cash runway and strategy to successfully fund the Phase III program here?

Yes. So we reported last June, in the quarter, $18 million on the balance sheet. Small pharma, of course, before that about the same time, $13 million on the balance sheet. We've also, since then there has been publicly reported had an investment from 0.72 Asset Management. That's -- basically came in on our ATM. So that was a very helpful pharmaceutical balance sheet. So we're in good shape at the moment. With good operating runway. And of course, as we get into Phase III, likely and these other studies as well, we'll likely have to look any more to the balance sheet at the [indiscernible].

It appears there are no further questions at this time. I will now turn the program back over to our presenters for any additional remarks.

That's wonderful. Thank you, operator, and thank you to all of our analysts for the great questions. Thanks to everyone for attending and paying attention today, and this is a very exciting time because Cybin, I think, it's a very exciting time for the sector. It's great to see the sector maturing and robust clinical data being published. And as I mentioned, several more readouts to come towards the end of the year and into early 2024. So I'll watch out for those, we'll give you an update at the appropriate time. So thanks for joining, everyone, and have a great day.

This does conclude today's program. Thank you for your participation. And you may disconnect at any time.