Earnings Call Transcript
COMPASS Pathways plc (CMPS)
Earnings Call Transcript - CMPS Q3 2021
Stephen Schultz, Senior Vice President of Investor Relations
Thank you, operator. Welcome all of you, and thank you for joining us today for our conference call today, which will combine both the third quarter 2021 results and the much-anticipated COMP360 Phase IIb top line results. We're able to combine these two events as they coincided from this timing standpoint. Again, my name is Steve Schultz. I'm the Senior Vice President of Investor Relations at COMPASS Pathways. And today, I'm joined by George Goldsmith, Chairman and Chief Executive Officer; Dr. Guy Goodwin, our Chief Medical Officer; and Piers Morgan, our Chief Financial Officer. The call is being recorded, and it will be available on the COMPASS Pathways' Investor Relations website shortly after the conclusion of the call. We hope you've had a chance to view the two press releases issued earlier today, one on the Phase IIb clinical result and the other covering our third quarter results. We've also posted a presentation to the Investors section of our website in the Events section that supports the top line Phase IIb data presented in this webcast, so you can follow along. Additionally, there’s an excellent COMP 001 Phase IIb hub on our website in the Clinical section, and I encourage you to check that out as well. Before we begin, let me remind everyone that during the call today, the team will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as amended. You should not place undue reliance on these forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those risks and uncertainties described under the heading Risk Factors in our annual report on Form 20-F filed with the U.S. Securities and Exchange Commission earlier today and in the subsequent filings made by COMPASS with the SEC. Additionally, these forward-looking statements represent our views only as of today and should not be relied upon as representing our views at any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements.
George Goldsmith, Chairman and CEO
Thank you, Steve, and welcome, everyone. I'm pleased to be here today to present both the top line results of our Phase IIb clinical trial of investigational COMP360 psilocybin therapy and our third quarter results in one webcast, which I hope makes it more convenient for all of you. Before going into the Phase IIb result, which I know is the star of the show today, let me first begin today's call with a business update on our recent progress. I will then ask Guy Goodwin, our Chief Medical Officer, to discuss the top line results of the COMP360 trial; and Piers Morgan, our Chief Financial Officer, to provide a financial review. We will then open the call to questions. This has been an exciting quarter. We’ve made great progress on numerous fronts. Last month, we presented positive data from an open-label investigator-sponsored study from the Maryland Oncology Hematology Group at the Aquilino Cancer Center in Rockville, Maryland. In this study, the team also pioneered simultaneous group administration with two to four participants being given psilocybin at the same time with one-to-one therapist support. This tested the value of group support for cancer patients with moderate major depressive disorder as well as the potential for increased scalability in providing psilocybin therapy in real-world settings. Most importantly, some participants benefited from this study while expanding our knowledge on how to improve future research for this population of special interest in MDD. In our goal to continue to expand our development pipeline, last week, we announced the launch of a study in post-traumatic stress disorder, or PTSD. This will be a COMP-sponsored Phase II program and should begin in the next month or so. Over 350 million people worldwide suffer from PTSD with an individual lifetime prevalence of 7.3%. In addition to the COMP360 development programs that include our academic programs, we continue to expand our leadership in preclinical research, exploring new psychedelic compounds through the COMPASS Discovery Center, a network of leading scientists from the University of the Sciences in Philadelphia, UC San Diego School of Medicine, and the Medical College of Wisconsin. Notably, we have engaged Hamilton Morris, the research scientist and filmmaker, as a full-time consultant who will be working primarily at the COMPASS Discovery Center. Hamilton will be advising COMPASS on research related to new psychedelic compounds that could be developed into therapies in areas of unmet mental health need. This early-stage work will enable us to broaden our portfolio beyond COMP360 psilocybin therapy. In September, we announced the acquisition of an intellectual property portfolio, including patent applications, covering a variety of psychedelic and pathogenic substances, some of which are prodrugs, pharmacologically inactive compounds that are metabolized inside the body to produce an active drug. The IP was developed together with inventor Dr. Matthias Grill who will be working with COMPASS on an exclusive research project to develop new product candidates. We plan to move some of these compounds into clinical development within the next two years, further expanding our leadership in this area of science. We also continue to grow our capabilities in digital and clinical innovation. Our digital team now comprises over 20 data scientists, engineers, developers, and designers. They are working on developing tools to improve the patient experience, train and support therapists, and explore digital behavioral markers. Some of these tools will be incorporated into future clinical trials. Our clinical innovation team is also growing to refine our psychological support model across indications and prepare for the increased therapist training requirements across our expanding portfolio of studies. Before I hand the call to Guy to talk about our Phase IIb data, let me say on behalf of the COMPASS Pathways' founders, Ekaterina Malievskaia, Lars Wilde, and myself, we applaud the extended team of so many people who worked on this trial, including clinicians, COMPASS employees and our clinical research organization partner, Worldwide Clinical Trials. Most importantly, we want to thank the patients who participated in the trial, enabling us to advance the understanding of how we can help others. I want to especially recognize Sue Stansfield, COMPASS's SVP of Clinical Operations, for her incredible contribution. This was a complicated and novel trial, and it was expertly managed in the midst of a global pandemic across 22 sites, 10 countries, and 7 languages. It's an extraordinary accomplishment and creates a foundation for the expansion of our clinical development program across indications of significant unmet need. Thank you, Sue. This achievement would not have been possible had it not been for those who were exploring psilocybin therapy before COMPASS. And we want to recognize those researchers, our new shoulders we stand upon today. These include Robin Carhart-Harris, David Nutt, Roland Griffiths, George Greer, Charles Grob, and Dave Nichols, among others. I also want to personally recognize Anna for her leadership in the design of our program and training protocol. Without her insight and determination, COMPASS would not be here today. With that, let me now hand over to Guy, who will provide a more detailed view of these results.
Guy Goodwin, Chief Medical Officer
Thank you, George. It's a pleasure to speak to everyone today and review the positive data generated from the COMP360 Phase IIb clinical trial, COMP 001. I'll be referring to the slides on our website that Steve referred to earlier, and Slide 2 is where I'll start, our COMP360 psilocybin therapy. Our COMP360 psilocybin therapy consists of two components. The first is the investigational drug itself, which is presented in oral capsules. And the second is the psychological support which consists of the preparation phase, support during psilocybin administration, and the subsequent integration. This, in total, is the psilocybin therapy that is being tested in this study. It is important to point out that this approach is developed as an integrated therapy, and the results from this trial can only be interpreted in this context. Other forms of psilocybin on their own or with some alternative support therapy protocol are unlikely to be comparable. Slide 3 is the COMP 001 study design and endpoints. Looking at the trial design and endpoints, you will see that all patients were screened and subsequently entered into the study within 3 to 6 weeks. This preparatory period was to allow the managed withdrawal of antidepressants, which the patients may have been taking. Bear in mind that these patients were all resistant to treatment with previously administered antidepressants and, therefore, had to be washed out before COMP360 could be administered. The randomization was to one of three doses, which were either 1 milligram, 10 milligrams, or 25 milligrams of COMP360 and were administered as you can see here on day 1. The effects of the treatment intervention were measured on day 2 at week 2, week 3, week 6, week 9, and week 12. The primary endpoint was designated to change in the MADRS score, the gold standard rating scale for depression at week 3, with a further important outcome at week 12 for the same measure to assess durability of effect. Randomization was equal to three arms of the study. Importantly, the MADRS score was assessed by independent raters who were remote from the trial site and blind to intervention and study design, effectively creating a triple-blind. Slide 4 shows participant disposition and demographics. In all, 233 patients were randomized, and they were allocated to the three arms of the study as shown on the slide. The numbers in each arm were as follows: for the high dose, 25 milligrams, 79 patients; for the intermediate dose, 10 milligrams, 75 patients; and to the low dose, 1 milligram, 79 patients. Of these patients, the majority completed the study, and a few discontinued in each of the arms; 5 in the 25-milligram arm, 9 in the 10-milligram arm, and 10 in the 1-milligram arm. So we know that there were more withdrawals in the arms with lower dose treatment, and the reasons for the withdrawals are shown on the slide. In all, there were 131 patients from Europe and 102 from North America. We were delighted to see that 94% of the patients had no prior psilocybin experience. So this confirms that there is generally a psilocybin-naive patient population, and this is a percentage which reflects community surveys in Western countries. The participant demographics, that is age, gender, race, weight, and baseline depression severity were all well-balanced across the three groups. Patients were moderately or severely depressed and, of course, met criteria for treatment-resistant depression. Slide 5 shows the primary endpoint change from baseline in MADRS total score. Again, the primary endpoint in this trial is the change from baseline in the MADRS total score at 3 weeks. We are pleased to report a statistically significant primary endpoint at 3 weeks. That is the comparison between 25-milligrams with 1-milligram as a magnitude of 6.6 points in the MADRS and a p-value of less than 0.001. Additionally, there was a rapid onset of actions seen as early as day 2 and the effects were sustained with statistically significant treatment differences between the 25-milligram and the 1-milligram group apparent from day 2 through to 6 weeks. In contrast, the 10-milligram dose showed an intermediate response of 2.5 points on the MADRS and was not statistically distinguishable from the 1-milligram dose at 3 weeks or subsequently. Slide 6 shows the key secondary endpoint, MADRS responders. Looking at the key secondary endpoints, the first chose MADRS responders. MADRS responders were defined as patients that experience a 50% or more reduction in symptoms at any particular time point. You can see the results presented for day 2, week 1, week 3, week 6, week 9, and week 12 across this graph. In every case, the color code remains the same, with the 25-milligram dose showing as the blue columns, 10-milligram as the green, and 1 milligram as the gray. It is evident from this plot that there is an important numerical difference between the 25-milligram and the 10-milligram and 1-milligram doses at all time points, the most important being week 3, where 36.7%, that is, 29 of 79 patients had shown a response at that time point in the 25-milligram group. This compares with about half the response rate in the other two groups. At week 12, there were 26 of 79 patients or 32.9% of the 25-milligram group that continued to show a response at this time point. Again, this was twice the number shown for the patients in the 10-milligram and 1-milligram groups. We believe this is evidence for the durability of response to the 25-milligram dose of COMP360 psilocybin therapy. Slide 7 shows the key secondary endpoint as MADRS remitters. Looking at MADRS remitters, those were defined as patients that in any particular visit shows a MADRS score of 10 or less. This is of particular clinical interest because it is evidence of beneficial reduction of symptoms to normal levels. You can see here with the same color coding for the results from different days that the rate for remission in the 25-milligram group at 3 weeks was 29.1%, and at 12 weeks, the rate was 26.6%. Bear in mind, this represents 23 and 21 patients, respectively, who remained without additional treatment and were in remission at weeks 3 and 12. By contrast, the numbers in the other treatment groups are lower. Slide 8, titled MADRS sustained responders. A further way of evaluating durability of response is to look at patients who individually met response criteria at a minimum of three visits. So both week 3 and week 12 together with at least one other visit at week 6 or week 9. When you select that patient group, they represent 24.1% or 19 of the 79 patients entering the treatment arm with 25 milligrams. As you can see, less than half that number in the 10-milligram and 1-milligram arms. Slide 9 shows safety. These are treatment-emergent adverse events. Looking at the safety profile and the treatment-emergent adverse events recorded in the study, which in over 90% of cases, were of mild or moderate severity. The patients reporting serious treatment-emergent adverse events were 5 patients in the 25-milligram, 6 in the 10-milligram, and 1 in the 1-milligram arm. As expected, the total number of adverse events were slightly higher in the 25-milligram group than either of the other groups. Further analysis on the onset and duration of the treatment-emergent adverse event is underway. Of particular interest will, of course, be the onset and duration because we are showing here treatment-emergent events over the whole duration of the study at 12 weeks. This total includes all events that are likely to be related to the psychedelic experience on the dosing day. We know from our healthy volunteer studies and from the literature, we should expect adverse events on that day. They have to be taken into consideration in evaluating the results of this trial. Slide 10 shows the most frequent treatment-emergent adverse events ordered by the 25-milligram arm and at least 5% in any treatment group. The most frequent adverse effects are shown here ordered by the 25-milligram arm. We’re showing all those adverse events that were shown by at least 5% in any treatment group. The most prevalent are headache, nausea, and fatigue, together with insomnia and then a variety of other adverse effects, which may well be related to mood. These are regularly observed in many clinical trials in depression. Next slide, Slide 11, shows treatment-emergent serious adverse events ordered by the 25-milligram arm. When looking at treatment-emergent serious adverse events, this is ordered again by the 25-milligram arm. There were relatively few events reported. As you can see, a number of them relate to suicidal behavior, suicidal ideation, drug withdrawal, and self-injury. These can all be common in patients with treatment-resistant depression. The number of events includes some cases in an individual patient and essentially part of the same episode, which are nevertheless classified as separate events for complete clarity. The conclusion is shown on Slide 12. In conclusion, this is the largest randomized, controlled double-blind psilocybin therapy trial ever conducted and it showed rapid and sustained response for the 25-milligram dose level of COMP360 psilocybin therapy. It's also worth noting that it is a multicenter study. It involves multiple patient populations recruited through conventional medical care systems, and very few of the patients had prior psilocybin experience in contrast to previous investor-initiated studies. We expect the top line data with secondary analysis will provide the springboard for Phase III development. The study achieved its primary endpoint with 25 milligrams achieving a significant treatment difference of minus 6.6% on change from baseline from MADRS scores when compared with the 1-milligram dose at week 3. The p-value for this effect was less than 0.001. The 10-milligram, interestingly, did not show a statistically significant difference at week 3 compared with the 1-milligram dose, the numerical difference being minus 2.5 points. The 25-milligram group demonstrated a significant decrease from baseline in the MADRS total score, the day after COMP360 administration. At week 3, the 25-milligram group showed a 12-point reduction from baseline in the MADRS total score. Secondary endpoints suggested at least double the number of MADRS responders and sustained responders was seen with the 25-milligram dose compared with the 1-milligram and there was a rapid development of remission from day 2 to week 3. The number of patients who showed a response was 29 of 79 patients in the 25-milligram arm, and 23 of 79 patients were still in remission at week 3. 19 patients of the 79 patients from the 25-milligram group were sustained responders at week 12. Regarding safety, COMP360 is generally well tolerated, and the majority of the treatment-emergent adverse events were mild to moderate in severity. We are particularly interested in understanding the reports of suicidality and suicide behavior in treatment groups. Finally, let me echo George's thanks to the team, our clinicians, and especially our patients who were involved in this trial. This result brings us one very important step closer to our goal of providing TRD patients with a novel and potentially life-changing option for many individuals who currently have very few options.
Piers Morgan, Chief Financial Officer
Thank you, Guy. The company continues to maintain a strong financial position with cash and cash equivalents of $294 million at September 30, 2021, compared with $190.3 million at December 31, 2020. This is expected to fund our operations into 2024. I will now recap our financial results for the three and nine months ended September 30, 2021. The loss from operations for the three months ended September 30, 2021, amounted to $21.8 million compared with $13.5 million for the prior year period. The loss from operations included non-cash share-based compensation expense of $2.3 million for the three months ended September 30, 2021, compared with $5.2 million non-cash share-based compensation in the prior period. The net loss was $15.8 million or $0.38 loss per share for the three months ended September 30, 2021, compared with a net loss of $16.7 million or $1.30 loss per share during the same period in 2020. The loss from operations for the nine months ended September 30, 2021, amounted to $54.9 million compared with $39.9 million for the prior year period. The loss from operations included non-cash share-based compensation expense of $5.9 million for the nine months ended September 30, 2021, compared with $16.6 million non-cash share-based compensation in the prior period. Research and development expenses for the nine months ended September 30, 2021, amounted to $30.4 million, an increase of $11.6 million compared with the nine months ended September 30, 2020. This increase in research and development expenses compared with the prior year period was primarily attributable to an increase in development, personnel, and consulting expenses as the company continues to expand its activities, including launching a new trial in PTSD, preparing for Phase III trials in TRD, and expanding our digital activities. General and administrative expenses were $24.5 million for the nine months ended September 30, 2021, compared with $21.1 million for the same period in 2020. The increase of $3.4 million in general and administrative expenses compared to the prior year period was primarily attributable to increases in personnel costs to support our growth initiatives, including our transition to a public company, increased insurance and other costs of operating as a listed company, partially offset by a decrease in non-cash share-based payments. The net loss was $46.1 million or $1.17 loss per share for the nine months ended September 30, 2021, compared with a net loss of $41.5 million or $3.90 loss per share during the corresponding period in 2020.
George Goldsmith, Chairman and CEO
Thank you, both. We're now working to schedule an end of Phase II meeting with the FDA as quickly as possible. I remind you that we have breakthrough therapy designation, which can provide us with a more rapid and open dialogue with the FDA. Our immediate goal is to present these data to the FDA and gain agreement on a Phase III program design. We will report on our progress in future communications. In addition, we expect the SSRI drug interaction study to be completed by the end of this year, which will provide important information about the potential influence of concomitant SSRI use with our COMP360 psilocybin therapy. You will recall that our Phase IIb study did wean patients off of their SSRI therapy prior to the COMP360 psilocybin administration session. Overall, this trial's result is consistent with the data we saw coming from the Imperial College London study in April and the recent Aquilino Cancer Center data, which is to say the patients saw a rapid and sustained effect with a generally well-tolerated safety profile. We believe this consistently supports our assertion that COMP360 therapy can potentially bring a new approach on how we may be able to treat patients for whom a few options exist today, and today's result continues to bolster our leadership in this field. To be clear, all of our efforts are aligned with our commitment to think differently about mental health and to follow up those thoughts with well-executed actions. The need is great. Patients are suffering. We have to provide them with new tools in the most responsible way. That means we must understand who can benefit from our work and who cannot at this point. We are working day and night to ensure we expand our understanding.
Ritu Baral, Analyst
Congratulations on the entire data set, not just the top line, but especially that remitters analysis. My first question, and I'll keep the second one really tight. My first question is Slide 11, the TEAEs, the venture preferred terms; can you go into a little more detail about what was seen around the individual behaviors, like when did they occur? Were these patients responders or remitters? And were they on rescue meds, especially suicidal behavior, self-injury, and ideation, I think are the most concerning to investors?
George Goldsmith, Chairman and CEO
Great, Guy?
Guy Goodwin, Chief Medical Officer
So the suicidal behaviors were really reported at least one month after the administration of treatment, and they occurred in patients who were essentially nonresponding. The suicidal ideation was a little different, and that was at least in one case was quite early on in the treatment process. Of course, these numbers are very small. Our plan is to look at them in as much detail as we can. But in addition, in the secondary analysis to look at the Columbia suicide scales that were collected on every patient at every visit, that will give us, I think, a much more accurate understanding of the relationship between treatments in suicidal ideation and suicidal action.
Ritu Baral, Analyst
The intention of self-injury, is that, I guess, an aspect that is overlapping with the suicidal behavior and suicidal ideation?
Guy Goodwin, Chief Medical Officer
We actually don't believe it does. It's classified in that way, but it represents really quite trivial self-harm. It means scratching or banging the head or very simple things that really don't carry any suicidal threat or intent, but they are quite common in depressive populations. They're well described and I'm afraid they're just part of the picture for these patients in part of that suffering.
Ritu Baral, Analyst
Got it. And a very quick follow-up, George and Guy, do you have your dose now? And do you think that a Phase III with the dose or powering a Phase III for durability, whether it's week 8 or week 12 would make sense for Phase III from a reimbursement perspective?
George Goldsmith, Chairman and CEO
Yes, we think we conclusively have our dose. In speaking with payers and others, we have included even in our Phase IIb trial health economic-related measures, quality of life measures. And we'll be discussing all of this as we go into our Phase III side with those who advise us on payer metrics, et cetera. We've been working with payers and health technology assessors here in Europe since 2016. So we’re well aware of their requirements, and we expect to be able to address that in a well-powered study. But obviously, our Phase III program will have to be agreed and discussed, which we've been discussing already with regulators on both sides of the Atlantic. We look forward now to bringing these data to then agree on that program and swiftly move into its execution.
Joshua Schimmer, Analyst
How are you thinking about ways to preserve effect beyond the first few weeks, either with the use of adjuvant therapies or patient selection to optimize for durable effect?
George Goldsmith, Chairman and CEO
Josh, I'll start to answer and hand off to Guy. I think it's a really important question. When we started this whole program, our whole goal was to identify who responds and who doesn't and who responds longer and who needs additional support. To that end, what we've done is actually recorded every therapy interaction. So we have machine learning out looking at transcripts across the site to look at trial participants really starting to understand the deeper level of patterns, including changes to patient narrative and therapist actions that are then correlated with particular outcomes. This is unprecedented data and we'll be digging deep into that to look at how we can, in fact, optimize therapy and develop, as we've said from the beginning, a more precise and predictive model of care with psilocybin therapy. So we're looking deeply at these data. But keep in mind, we just received the data about 48 hours ago. So there’s a lot of work to do. We're just reporting top line today.
Guy Goodwin, Chief Medical Officer
I think I’d just underline that the way in which this study was designed is that the psychological support is essentially safety around the administration of the medication. So this is a test of the medication in isolation. It’s pretty remarkable that we get these effects after a single dose after 12 weeks. Clearly, if we are working with colleagues within the company to look at digital support mechanisms and monitoring, which may very well have to carry the promise that we can improve outcomes through that sort of approach, then we’ll certainly be considering that in the future.
George Goldsmith, Chairman and CEO
I should just also say that this is the data set that we developed in close collaboration with payers and regulators, again, on both sides of the Atlantic in over 10 countries to answer the fundamental questions, and we couldn't do that unless we really looked at the dose finding and a single dose of its durability. Only then can we look at how we can identify the patients who have different experiences and look at how to optimize that experience to maximize the outcome and the duration.
Joshua Schimmer, Analyst
Got it. And when do you expect to have some of the additional analysis completed in the full data presentation?
George Goldsmith, Chairman and CEO
We'll be working on that part and doing it as soon as possible. We don't have a date, but you know us; we're going to be at an intensity and vigor.
Charles Duncan, Analyst
Okay, George and team, congratulations on a rigorously conducted trial. It's clearly a seminal event for the field. My first question is regarding next steps on sizing and timing, and I know you need to discuss this with the agency. But could you imagine being able to outline a protocol or even operationalize a next step, maybe a Phase III by roughly mid-'22?
George Goldsmith, Chairman and CEO
We can certainly imagine many things, and that's one we're focused on imagining, to use your term. We are very heavily recruiting sites and looking at preparing our Phase III infrastructure to build on our really robust Phase II infrastructure. That work is all in process. But again, we can't anticipate what the agency, the FDA and the EMA and HRA will say as we review these data. So we are ready to hit the go-fast button as we do whenever we get the word from the agencies. But we will be reviewing this very rapidly with them.
Charles Duncan, Analyst
Okay. That's good, George. Second question is regarding any phenotypic factors. I understand that this is fresh data, so probably haven't done the analysis. But is there anything that you're in particular interested in, such as prior lines or time since their diagnosis that may have driven responses in terms of either the primary endpoint or durability? Anything that you're particularly interested in looking at where you've seen?
George Goldsmith, Chairman and CEO
Again, I will start that and then hand off to Guy. I think a few things were really important to us. One was that this study actually used patients who were referred based on medical records. So we have a validated background, and that background information will be used in future analyses, obviously. One of the things that was really important to us was to be able to demonstrate that these benefits could happen to people who had no prior experience or 94% of our sample had no prior psilocybin experience, quite unlike the prior studies. The majority of our therapists in all of our centers also had no prior psychedelic experience. This was so important for us to generalize in all of the population, which is approximately the same in our study, about 90-plus percent who haven't had these experiences. So to be able to demonstrate that this works in that environment, it's really important for scalability and, more importantly, to help the most patients possible.
Guy Goodwin, Chief Medical Officer
Yes. Just to say that, obviously, we're aware of existing data that suggests that one can, to a limited extent, predict treatment response from baseline measures, and we have those baseline measures. There’s also, of course, emerging interest in biomarkers, and we'll be looking at the measures that we have in that category as well. But as you rightly said at the beginning, we're not yet in a position to comment on that. We're just going to be very excited to follow up and look at those questions and answer them for you.
Charles Duncan, Analyst
Okay. Last quick question, then I'll hop back in the queue. Referring to Slide 6 and 7 in terms of remitters or responders and remitters. It looks like weeks 6 and 9 numerically are a little bit less than week 12. I guess I'm wondering if you think that's an artifact of the remote visit or if there's something else going on there with the drug. It's hard to imagine what that might be. But tell us about that and tell us how you would use those learnings in the future trial designs.
Guy Goodwin, Chief Medical Officer
Well, I think in general, we feel that the data from weeks 6 to 9 and 6 to 12 gets slightly more difficult to interpret because there is additional treatment going on in the three treatment arms with some of the patients. So that's a factor that we've had to consider, and we're going to have to analyze more closely. So I think we feel very confident about the statistical differences up to 6 weeks that we're encouraged by the group to receive no treatment. But we need to understand the whole data set. We're going to have to take into account the fact that antidepressants were available for use and in some cases were used in all three arms of the study.
George Goldsmith, Chairman and CEO
I should also add that one other thing where we need to look at, this study was conducted through the very depths of the pandemic with people being in lockdown, and we'll be also looking at are there any effects of when the lockdown is occurring on patient populations, et cetera, because that's quite an unusual event; it very likely had many mental health sequelae for people. So we are going to be looking at that. It's an unusual thing to have to consider in a trial that’s quite meaningful. So standby.
Esther Hong, Analyst
Congratulations on the data, really impressive. Wanted to ask about patients who had to discontinue antidepressants prior to the administration of COMP360. Any additional details on these patients and perhaps regarding washout periods and response rates and remitter rates? And then I've got a follow-up.
Guy Goodwin, Chief Medical Officer
Yes. All the patients were taken off antidepressants, and we will provide more details on how long the washout took and the delays between starting that process and the actual dosing day. You raised a very interesting question. There is significant interest in the effects of discontinuation. We think that stopping treatment in patients who were highly symptomatic and treatment-resistant was fairly straightforward to generalize, and generally successful and acceptable to patients. Many of them remained off antidepressants for the next 12 weeks as well.
Esther Hong, Analyst
Right. Got it. And then just quickly, can you remind us what biomarkers you're looking at?
Guy Goodwin, Chief Medical Officer
We have polymorphism in the 5HT2A receptor that may be of interest to the drug action. We're also interested in an inflammatory biomarker, which will be informative as well.
Patrick Trucchio, Analyst
Congrats on the results. I have a follow-up question on the suicidal behaviors. I'm just wondering, what was the protocol definition in terms of how far out post the exploratory session? Could this be considered attributable to the treatment? Is there a limit to that? Is it within the 12 weeks? And is that something that's consistent across TRD studies? Or was this unique to the Phase IIb trial for COMP360?
Guy Goodwin, Chief Medical Officer
At any point during the 12 weeks, any occurrences of suicidal thoughts or behaviors were noted, along with the timing of those events. Although the numbers are very low, making the estimates uncertain, they are similar to most studies conducted on depression. A recent meta-analysis indicated that the average rate of suicidal events among actively treated patients was around 3%. Therefore, our figures seem to be roughly consistent with that rate. It's important to remember that this group is expected to have a risk of emerging suicidality due to their background.
Patrick Trucchio, Analyst
Got it. That's helpful. And then I'm just wondering if there was any learnings that have heard from the study or some of the others that have read out recently in terms of feasibility of simultaneous treatment or therapy. I'm also wondering if you think you would need a separate Phase II trial to assess the feasibility of simultaneous therapy? Or could this potentially be a step for treatment arm in the Phase III program?
Guy Goodwin, Chief Medical Officer
I don't believe we're at a point where we can provide an answer to that. We will have experience administering 25 milligrams of psilocybin therapy to patients still on SSRIs in a small open-label study, which will be reporting soon. After that, we will be better positioned to make an informed judgment regarding your question.
George Goldsmith, Chairman and CEO
I would like to add that as we explore areas with significant unmet needs across various indications, our goal is to become a learning organization and continuously apply our insights in real time. This approach will enable us to advance our clinical studies and maximize benefits for patients. We are focused on constructing a pathway that connects smaller studies to larger ones to facilitate learning.
Sumant Kulkarni, Analyst
Thank you for all the company's work on what must be an exciting day for patients who might see another treatment option for TRD. I have three questions. I'll ask them individually. First, based on what you now know with your Phase IIb data in hand, are there any specific variables that you instantly see in terms of needing adjustment for your upcoming Phase III program?
George Goldsmith, Chairman and CEO
Guy, do you want to start with that?
Guy Goodwin, Chief Medical Officer
I don't think instantly, we see anything we need to adjust. But obviously, we're reflecting on a whole series of issues that are raised particularly when we look at the secondary analysis. What is your reaction, George? That's mine.
George Goldsmith, Chairman and CEO
Yes, it's mine as well. Again, these are very, very fresh results. We have the largest data set ever created in this area. We have an incredible team, statisticians, and data scientists. We're really looking at all of that and taking that into discussions with regulators and devising the path forward.
Sumant Kulkarni, Analyst
Got it. My second question is, sorry, go ahead.
Guy Goodwin, Chief Medical Officer
No, it’s fine. No, I was just going to say that you appreciate the top line results are all driven by a very, very strict and conservative analysis plan. So that’s a sort of limitation on how far one can immediately react to differences.
Sumant Kulkarni, Analyst
Understood. So second question. Given your work with patients, physicians, payers, and other components of the supply chain so far, what do you think would be the sweet spot for durability and COMP360 that in the real world?
George Goldsmith, Chairman and CEO
Well, I think that everyone's dream is to actually look at how we can predict and prevent relapse. We're hard at work looking at new tools that might help with that and digital phenotyping. But I think that people understand today that this is an incredibly difficult patient population to support and serve. It was a single administration of monotherapy. We see great promise at 3 weeks as well as 12 weeks, considering the lives of these people. So we'll be in lots of discussions, and I think we'll come back to that question with more information in the not-too-distant future as we start finalizing our Phase III plans.
Sumant Kulkarni, Analyst
And my last question is, should we expect to see any difference in response to COMP360 based on the specific antidepressant used or failed by patients in the past?
George Goldsmith, Chairman and CEO
We have no idea what to expect because it's an empirical question. Fortunately, we have data to be able to answer it.
Robert Hazlett, Analyst
Congratulations on a well-conducted and important study. I have a couple of questions to better understand the patient characterization of this study. Could you provide the baseline MADRS rates for either the study as a whole or any of the specific groups?
George Goldsmith, Chairman and CEO
Yes. Yes. I think it's on...
Guy Goodwin, Chief Medical Officer
Yes. It's on Slide 5 if you want to refer to it. It's written rather small and it's very easy to miss. All the data you requested is on Slide 5.
Robert Hazlett, Analyst
Okay. And then just with regard to geographical groups, are there any notable similarities or differences within the particular patient groups, either in North America or in the U.S? Or excuse me, in the U.S.?
Guy Goodwin, Chief Medical Officer
We'll be looking at that with great interest. So we haven't been on that.
George Goldsmith, Chairman and CEO
I was just going to say what's really remarkable about this is we've trained therapists in 7 languages, 10 countries and demonstrated these results across the board. It's going to be fascinating to look at all sorts of cuts in terms of demographics, countries, etc. But we were amazed and I think also amazed at the levels of recruiting and engagement we have in the Netherlands from our sites. And so I think that was also a very interesting characteristic, given the availability of other substances there. So this is clearly an unmet need and a high level of interest in the trial.
Robert Hazlett, Analyst
And then just one more for me. With regard to the serious treatment-emergent adverse events, do you have any more information at all with regard to the time course of those events, just in general characterization? Were they closer to the administration and maybe waned further on? Or just, again, any anecdotal characterization you might be able to make with regard to those?
Guy Goodwin, Chief Medical Officer
It wasn't simple. Every patient tends to have their own complexity, as you probably appreciate. The suicidal behaviors all occurred at least a month after the drug administration, so we can certainly say that from this data. Some of the ideation occurred closer in a couple of cases. But I want to emphasize again that we will get much more detailed data when we analyze the ratings of suicidality in the secondary analysis. We will certainly share that information with you as soon as we have it.
François Brisebois, Analyst
Just wanted to ask, in terms of the placebo effect, was that based on literature and your expectations, mostly in line just based on the potential negative placebo effect here and the triple blind that you mentioned?
Guy Goodwin, Chief Medical Officer
We didn't have much to rely on, aside from previous crossover studies. We carefully considered our approach when designing this study. All participants were informed that they would have a psychedelic experience. We believed there would be a significant nocebo effect in the group receiving 1 milligram. However, we also recognized that they were receiving extensive psychological support, which could influence the results positively. The purpose of conducting experiments is to understand the outcomes. This is what we found, and we will analyze it to the best of our ability.
Elemer Piros, Analyst
Yes. George, you mentioned that you think you have defined the 25-milligram dose. Would you exclude repeat dosing within the clinical trials?
George Goldsmith, Chairman and CEO
Right now, what we're doing is trying to understand, as we said, each patient's experience. I think that will help inform thoughts along that line. But I think what we really needed to do with this trial was to actually establish a level of understanding of durability up to 3 months of a single dose. That will help inform a tremendous amount of analytics moving forward. Then I think we'll step back and look at what's required. I do know that if we have in the 21st century the ability to predict relapse and to preempt it, that's really the goal for us. We're hard at work, looking at those kinds of things, and aren't ruling anything out at this point. Obviously, lots to do and lots to discuss with regulators.
Elemer Piros, Analyst
Yes. And the last question is, how many sessions were integrated per data for this protocol, George?
George Goldsmith, Chairman and CEO
There were two.
Elemer Piros, Analyst
Two. And do you think that number is sufficient?
George Goldsmith, Chairman and CEO
Again, we have an amazing team working on all the transcripts, all the interactions, and creating an empirical response to that question. I think that one of the things that's really important is that we look at a very fine range precision approach to this, patient by patient, so that we really develop a plan for everyone. I think this is where we're headed. We'll be doing all those analyses and sharing what we learn and then informing our future plans.
Neena Bitritto-Garg, Analyst
So I just wanted to ask about the use of rescue meds in the follow-up period. I guess can you talk a little bit more about when patients were allowed to start taking rescue meds? And then anything you can share at this point on the actual rates of use of rescue meds in the different arms, that would be great.
George Goldsmith, Chairman and CEO
Sure. I just think that Guy, when you talk, you should probably make a clarification or start with the clarification of rescue versus other medications.
Guy Goodwin, Chief Medical Officer
Yes. Our understanding of rescue would be the use of medications on the day of the study, the day of the dosing. If my memory serves, there was only a single example where that was necessary. That means we were successful at delivering the actual dosing day without having to rescue patients from the experience. We think that the therapist did a great job. The other sense in which there's rescue medications is that these patients have been withdrawn from antidepressants. We had to expect in advance that there would be a pressure for them to go back on to antidepressants if they showed no response or limited response to our treatment. That would apply in all three arms of the study, of course. However, we did encourage the clinicians entering the trial to give the treatment a fair trial after three weeks as far as they could. After that, they were free to use medication if they felt it was clinically indicated. So we've got a picture that we've not yet fully analyzed of the number of patients returning to antidepressant treatment. When we fully understand the patterns, we’ll publish them.
Michael Okunewitch, Analyst
So I wanted to ask if you could put the data in a bit of context because it seems like the magnitude of result is not as high as previous studies. Could this be somewhat owing to the fact this is a single-dose protocol? Considering that the patients and the clinicians were psychedelic-naive, should this be viewed as a more conservative study to establish that baseline for COMP360, which could be improved in a more optimized setting?
George Goldsmith, Chairman and CEO
That’s a challenging question to answer. We conducted this study primarily to address regulatory and payer concerns regarding the generalizability of the model. We believe this model is indeed generalizable and can be optimized in different ways that we are exploring. What sets this study apart is that it was multicenter and carried out with significant clinical and scientific balance, which is challenging to achieve in a single-site study. We employed a triple-blinded model, with an independent rater assessing each patient in their native language, fully blinded to the study. This aspect allows us to have confidence in the results, given the independent evaluation using the standard MADRS. We see this as a strong foundation to build upon, and we are definitely interested in further optimization.
Michael Okunewitch, Analyst
All right. And then I wanted to ask about how clinically meaningful the absolute reductions in MADRS and MADRS score, which were around, I think, minus 12 at week 3 and that stayed around minus 10 at week 12? And how does that compare to SSRIs?
Guy Goodwin, Chief Medical Officer
I believe the interpretation of the average change in the population is largely dependent on how clinical trials are viewed. I'm more concerned with individual patient experiences. When analyzing the data, the significant number of remitters after 12 weeks stands out to me as particularly relevant clinically. The comparisons between different deltas are intriguing, though they can be challenging to assess when the trials are not conducted in the same manner. I do acknowledge that our effects are noticeable from day 2, whereas SSRIs typically show their effects by week 6. They tend to measure only the time frame during which we demonstrate statistically significant results. From the data on Slide 5, you could observe that the difference between 25 milligrams and 1 milligram at that stage remains around 5 or 6 on the MADRS scale, while the average response in SSRI trials after 6 weeks is about 2 to 3. In terms of comparison, that is where I would place my assessment. However, we are addressing the TRD population, which has its own set of limitations, particularly those who do not respond at all to SSRIs and have, by definition, failed to respond to them.
Michael Okunewitch, Analyst
All right. And then just one more quick one, and I'll jump in the queue. For the suicidality, considering that, that was largely a month after, could that be related to a sense of hopelessness in patients that nothing worked for them so far and now they try psilocybin and they didn't respond to that either?
Guy Goodwin, Chief Medical Officer
Well, I think that's a consideration we'll certainly be taking into our deep dive into the data in the future. It's an interesting possibility, we agree.
George Goldsmith, Chairman and CEO
Yes. I think we will have to look also at the level of expectation that is set in the general press. I think this is something really important to take responsibility for that. There are no panaceas, and the study indicates that.
Stephen Schultz, Senior Vice President of Investor Relations
Sure. Let me hand it back to George for closing remarks. Please, George?
George Goldsmith, Chairman and CEO
I just want to thank everyone for their interest, participation, and support. This is something that is going to be the start of really developing what we view as a way to transform the patient experience and mental health. We're on it. We're working at how we can help reduce suffering at scale and appreciate all of your interest and support. Thank you very much.
Operator, Operator
That does conclude our conference for today. Thank you for participating. You may all disconnect.