Good morning, ladies and gentlemen, and thank you for standing by. Welcome to Cybin's Conference Call. At this time, all participants are in a listen-only mode. Following the prepared remarks, we will conduct a question and answer session open to financial analysts. Instructions will be provided at that time for you to queue up for questions. I would also like to remind everyone that this conference call is being recorded today, Wednesday, November 1st, 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. 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 grow 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 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 onset of effects aimed at short ened 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 for the FDA. We have the largest IP portfolio in the psychedelic drug development sector, with over 33 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. 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.
We plan to have four clinical trials upcoming in 2024, including a planned global phase III trial of CYB003 in MDD, and a phase II proof of concept study of CYB004 in generalized anxiety disorder, each beginning in early 2024. Additionally, we'll be running two formulation studies, a subcutaneous study for CYB004 and an intramuscular formulation study for SPL028, each with the goal of creating more convenient 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 a 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 antidepressant treatments, and suicide risk is 20 times higher for an individual with depression versus a person without. While SSRIs are the most common first-line pharmacologic treatment for depression, up to two-thirds of patients do not remit with initial antidepressant 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 option. 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 II-A MDD study, SPL026 delivered rapid onset of effects with a 7.4-point reduction in MADRS score at the two-week primary endpoint.
To put that into context, that's approximately four times what is typically seen from SSRI therapy. And impressively, 40% of MDD patients were deemed to be in remission at six months following one or two doses of SPL026, providing tremendous proof of concept for our deuterated DMT program. And when added to SSRI therapy, SPL026 was well tolerated, and with 92% of the SSRI group in remission at four weeks after a single dose. Just remarkable. These, these data sets are clearly impressive, and they go a long way in de-risking our deuterated DMT program. Today, we're showcasing the unprecedented positive phase II interim data for CYB003, with a focus on cohorts four and five, which each received a single dose of 12 mg of CYB003 or matching placebo.
The purpose of this phase II clinical trial was to evaluate safety and also efficacy using the MADRS scale or the Montgomery-Åsberg Depression Rating Scale. The primary efficacy endpoint was a reduction in depression symptoms and change from baseline in MADRS at week three 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 symptoms three weeks following a single 12 mg dose of CYB003 compared to placebo. Remarkably, 53.3% of patients responded, and 20% of patients went into remission, meaning they no longer met the clinical definition of depression. This compares to 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 25-65 years old, and it was an ascending dose cohort design. So the MDD 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 antidepressant medication, so this was an add-on treatment. The intent for cohorts one to three was basically to assess pharmacokinetics and safety and identify a dose at which strong psychedelic effects could be seen.
These were therefore smaller cohorts with four participants each, and two doses were administered in each of these cohorts. Cohort one was MDD patients, but we soon realized after cohort one that we needed to pivot to healthy volunteers for cohorts two and three. 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 receive either active drug, CYB003, or placebo in a nine to three 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 three-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 a regimen of two administrations three weeks apart, 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 three weeks. At the six-week time point, we have a further 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 one. 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'll see efficacy data for cohorts four and five at 12 mg, which we're showing you today. While we started seeing psychedelic effects at 3 mg and robust effects that were consistent with therapeutic efficacy, we already started seeing those at 8 mg
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 lasted for about two 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 two cohorts. The cohorts were fairly balanced in terms of age and gender. 18 were randomized to an active first dose, and six to the placebo. As you can see, they had comparable baseline MADRS scores, which was just about in the severe category.
Due to the fact that we administered two doses to each participant, we are eventually going to get about 78 exposures by the end of cohort six, even though we enroll only 48 participants. 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 indicates improvement, placebo being represented by the black line and CYB003 being represented by the teal colored line. The vertical lines or whiskers represent standard deviation, which is 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 three-week primary endpoint, 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'll appreciate is very large. And actually, maximal improvement was already evident as early as 10 days after dosing and was sustained up to the three-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 four to six 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 33, it's almost a 15-point reduction. Within three weeks, 20% of the participants went into remission. Remission was defined as single-digit MADRS scores, so scores 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, increase 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 three and far superior in magnitude to what is typically seen with other antidepressants, meaning we have a large effect size of 2.15. In contrast with the SSRIs, which are the standard of care, effect sizes are traditionally very small in decimals. 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 mg, 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 so 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 head comparison. However, if we look at 232 clinical studies of SSRIs since 1979, we see a mean reduction in depression score of less than two 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 II-B 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 psychedelic 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, were 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 depressive symptoms with a single dose, we're moving ever closer to delivering on our mission to improve the treatment landscape across a 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 with 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 one.
We also intend to initiate a U.S. phase II study in generalized anxiety disorder for our CYB004 DMT program, and with two 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.
At this time, if you would like to ask a question, please press star one on your telephone keypad. You may remove yourself from the queue at any time by pressing star two. Once again, that is star one to ask a question. We will pause for a moment to allow questions to queue. Our first question comes from Charles Duncan with Cantor Fitzgerald. Please go ahead.
Yeah. Hi, good morning, Doug and Amir. First of all, congrats on the interim results and also recent progress, and thank you for taking our questions. I had a couple on CYB003. 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, you know, 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 team-colored line. The vertical lines of whiskers represent standard deviation, which is representative of the sample size. As you can see, a single dose.
Sure. Amir, do you want to take this one?
Yeah. Yeah. 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 one or two. So the intention was we wanted to exclude habitual or frequent users of psychedelics. Now, so it was, in other words, a relatively psychedelic naive population. The other question, I think, was about background SSRIs, background antidepressant treatment, and yes, these patients were allowed to remain on their antidepressant treatments, which actually, putting that into context with the results, probably makes the results more impressive because it's always more difficult to show an incremental benefit over an existing therapy.
They, they stayed on their therapy. They probably also benefited from taking the antidepressant, their ongoing antidepressant, but importantly, that happened in the placebo group as well. So any advantage due to taking an antidepressant would have been negated by, in the placebo group, if that makes sense.
Yeah, it does. Really what I'm asking is whether or not background SSRI or SNRI-
Mm-hmm.
therapy impacted the effect size, like in patients-
Uh.
who were less experienced may have had a higher impact effect.
Yeah.
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 kind of results.
Yeah. Yeah. So first, the background treatment question. We didn't really anticipate any interaction in the sense of a pharmacodynamic or a 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 a 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 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 antidepressant.
This was 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 DMT data that Doug shared earlier, those people who remained 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 psychedelic. 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 tried to guess, in all honesty, and we got it wrong.
When you look at the visual analog scale scores, when you see scores around six, seven, you're thinking, out of ten, you're thinking, "Hmm, this patient probably is on an active drug." And we tried 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 received the drug, in a blinded manner, they had some effects mimicking psychedelic effect. So yeah, there's a risk of functional unblinding, but it seems that placebo really did its job as a comparator.
Okay. 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, you know, it seems to me that you could have less heterogeneity in terms of absorption, you know, maybe. I guess I'm wondering if you believe that could drive a relatively capital efficient, you know, phase II-B or phase III study, you know, in terms of perhaps fewer patients needed to define the effect size. And then thinking about this 12 mg effect size, pretty notable, versus one that you may see with 16, I guess, what—if you had to guess what your go-forward dose would be, do you, do you have a favorite?
So maybe I'll take this. Charles, thank you. Look, I mean, it's very clear from this data that 12 mg is an effective dose. You know, our goal with 16 mg was to see if we could get a few more patients across the line. As with any treatment, not everyone responds. While also trying to make sure we keep the, you know, the side effect profile in check. So we'll take a call on that once we see the full top line data, and we look at the two sets of data side by side, both efficacy and safety profile.
To answer your question about phase III design, yes, I think we can achieve a fairly efficient phase III study very similar to the phase II design, in that we'll be providing two doses of CYB003 three weeks apart, but no crossover in the studies. Just both of those doses compared to a pure placebo. That study at the moment, obviously, we will have to convene on this with FDA at the phase II, in the phase II meeting. But that study at the moment is intended to be around 220 patients. So a decent size, but not massive. So manageable, should be relatively efficient. Randomized 1:1.
So that study in our current draft design is has an 80% power to show a five. Even though we're 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 peer review, and we'll put the final draft in front of the FDA when we meet with them in quarter one of next year.
Can I clarify a point? 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 patient is on?
Yeah, thanks for the question and the clarification. So the population rate is anticipated to be the same. So moderate to severe patients with MDD that are also taking an SSRI or an SNRI. So you're right, both groups, both the active group and the placebo group, will be on background therapy, which we believe is representative of the real world.
Okay. Thanks for taking my question. Look forward to further updates. Thank you, Charles. Thank you.
The next question comes from Patrick Trucchio with H.C. Wainwright. Please go ahead.
Hi, everyone. This is Luis for Patrick. Thank you for taking our questions. How does CYB003 differ from other first-generation psychedelics? So is there any particular beneficial attribute that is coming from this specific generation relative to the older compounds? Is there anything on the mechanistic side that you can speak to?
Yeah. So we've been careful here, and thanks for the question, Luis. We've been careful not to modify the active parts of the compound. We don't want to change receptor binding profile. We don't want to impact efficacy necessarily adversely or side effect profile adversely. 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 with deuterium in a very specific way. Preclinically, we saw an increase in brain to plasma ratio, so higher concentrations in the brain and in the plasma when compared to psilocybin.
So, when we compared the two, we saw about a 40% increase in, brain to plasma ratio with CYB003 compared to regular psilocybin, and, and an increase in bioavailability. So it does appear that maybe those characteristics, the changes in PK, are driving an increase in potency. As Amir, as Amir said, we, we've seen really robust psychedelic effects at doses as low as 8 mg. So, compared to, say, a typical dose of psilocybin, which might be 25 mg. So although we haven't done that direct head-to-head in terms of, efficacy or potency, it's clear we're seeing effects at lower doses. And the same is true also with, with DMT.
And the benefits of other DMT is that we're able to put the dose into a very small volume, maybe a subcutaneous or injection or an intramuscular injection, and remove the need for expensive and technical equipment like an IV infusion pump, which most psychiatrists and psychologist therapists just don't have in their offices. So the deuteration is helping. It seems to be helping the potency here, and it's going to be helping with more convenient dose forms with DMT.
And a 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 treatments? So since you are using this on top of background therapies, I'll 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 and remission rates?
Yeah. So, yeah, I think it's clear when you look at the historical development in depression, it's really quite difficult to show incremental benefits on top of existing treatments. And most drugs approved are monotherapies for that reason. You know, I think that the last drug I can think of that was shown benefit as an incremental treatments and adjunctive treatments, SSRIs, for MDD was perhaps Abilify or aripiprazole. I believe peak sales of that product were around $6 billion-$7 billion annually. So there's a massive unmet need for patients that are not getting all the benefit they would need or like from their SSRIs. And we know that SSRIs don't work for everyone.
They do work for some people, don't work for everyone, and often people have breakthrough depressive episodes while they're still on the SSRI. So having another option on top of an SSRI, and to get a 53% response rate out of adjunctive therapy is pretty remarkable.
If I'm allowed 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 outline the phase II design in the short time. But once we have had that locked down, you know, it'll be a compared to placebo proof of concept study. You know, 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, we know that DMT is efficacious in MDD, then there's a high probability, we believe in showing efficacy in this group of GAD patients that have depression. And of course, when you look at anxiety disorders overall, they affect about 18% of the U.S. population. It's really a very large group of folks where current treatments are really, really, really not very satisfactory.
Great. Thank you so much.
The next question comes from François Brisebois with Oppenheimer. Please go ahead.
Hi. Thanks for taking the questions. Just so firstly, I was just wondering if you could comment about your placebo arm, one in the remission, and relapse, the 0%. And then also just in terms of, you know, the chart, in terms of the maybe the lack of variability or the, you know, very positive, you know, for your trial-looking placebo arm. Is there anything that you did hear, or do you think keeping them on SSRIs might have, you know, help explain it? Or is this just a small N number, and it's very hard to say why the placebo had quite a bit less variability, I guess?
Yeah. Amir, do you want to take this one?
Yeah. Yeah. 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. It's so high at three 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 that's due to small numbers, because with small numbers, you should actually have more variability. It's simply that people realize that they are not on the drug. And as you 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 you, the responder of 50% or greater in the treatment arm or the 0% in the placebo arm?
Well, clearly, responders, I would say. At three weeks, 50%+ responders is quite remarkable. We don't really see that with conventional treatments. It takes at least about six weeks to even assess, four to six weeks to start seeing some effects, and responders is like a 50% reduction in symptoms. That's quite remarkable.
Okay. And so-
Yeah, I'll just add to that.
Go ahead.
I'll just add to 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 and placebo groups of around 33, so in the 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 N number. Were there any dropouts here or anything to note?
Yeah.
Amir, do you want to take it?
Yeah, yeah. Between the two cohorts, we actually enrolled 24 patients. So, that was 18 on active and six on placebo, but we had three 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, per protocol completers, and on placebo it was six. 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 as regular psilocybin, or did the duration help reduce the time of therapy?
We're certainly seeing a fast onset. So, as we've reported before, onset of effects in about 15 minutes. So that does mean the patient's not waiting around and potentially having a bit of anxiety or even remorse that they've just taken something that's quite powerful. So that fast onset, we think, is good for patients. The peak effects last about two hours, so the peak therapeutic time is about two hours, so relatively short. And then the patients start to come down and start to recover. We haven't strictly measured the time from beginning to end because generally, you're trying not to disturb the patients, you know, during the session.
But we believe that based on anecdotal feedback from the facilitators, that we're in the 4-4.5-hour range, end to end, beginning to end. So, substantially shorter than some of the anecdotal times we've heard regarding, you know, psilocybin sessions, which could be six or eight hours, I believe.
Okay. If I could just sneak in a, a last one here. Would you, in terms of phase III, you talked about 220, 1:1. Could there be multiple phase IIIs, and would you ever look at-- You know, I know you, you said it'd be similar patients here on SSRIs, to a previous question, but would you ever look at, you know, weaning off patients of SSRIs or just going after a true placebo just to see if we can totally get rid of SSRIs? Thank you.
Yeah. So currently, we're sticking with patients that are taking their SSRIs. We think that that's a lower hurdle for patients and a lower hurdle for practitioners. You know, titration is difficult. It's quite challenging. The dose titration down is not linear. Many patients often go too far and have to take a step back. And then there are the reported rebound effects from titration coming off of SSRIs that may last up to a year. And those rebound effects may compound the study gap 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 FDA has made it fairly clear in their draft guidelines that they would like to see both a pure placebo, as we've used in this phase II study, and as we are planning for our first phase III. They also want to see a low dose or medium dose or some kind of dose ranging as well, to perhaps remove some of the nocebo effects. They tend to look at the complete data set from two phase III studies.
Thank you.
Thanks. Thanks for your question, Frank.
The next question comes from Sumant Kulkarni with Canaccord. Please go ahead.
Morning. Thanks for taking my questions. I have three. The first, did the compliance rate of background SSRI or SNRI therapy in either the placebo or the active group change over the three-week period in the phase II study? And going forward, how do you, how do you ensure that does not change?
Yeah, that's one for you, Amir.
Yeah. So, we're still to dig into those data, Suman. That will be out when we share the top line data in November, early December. But from reports from this, we have no reports from 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 it, 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 medications on time.
Often it's very, very difficult to make sure they take medications, same medication at the same time every day. 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'll collect those data and we'll 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 one or two doses of or three, three weeks apart as we wait for this phase II data set here?
Yes, we-
Yeah.
We will see. We will see. You know, we've worked here to try to design a treatment and a treatment protocol that is designed to do just what you're asking, Sumant, that is to extend the durability of effect. And 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 60 mg, and we're also, as you say, applying a second dose, you know, three weeks after the first dose. I would hope and expect that we might see an increase in response or remission rates with the second dose.
You know, some patients just don't get across the line the first time with psilocybin. It's a bit of a wavy experience. It's a very technical term. And some patients resist or are fearful or anxious and don't 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?
Yeah. So, we reported last June and ended the quarter $80 million on the balance sheet. Small Pharma, of course, reported about the same time $13 million on the balance sheet. We've also, since then, it's been publicly reported, had an investment from Point72 Asset Management. That investment came in on our ATM. So, that was very, very helpful, obviously, for the balance sheet. So we're, we're in good shape at the moment with a 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 at adding, adding more to the balance sheet at that time.
Thanks.
Thanks, Sumant.
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 for Cybin, and 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 watch out for those. We'll give you an update at the appropriate time. So thanks for joining, everyone, and have a great day.
Thank you.
This does conclude today's program. Thank you for your participation. You may disconnect at any time.