Good day, ladies and gentlemen, and welcome to the COMPASS conference third quarter call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question- and- answer session. To ask a question during that session, you will need to press star one one on your phone. As a reminder, this call is being recorded, and I would now like to introduce your host for today's conference, Stephen Schultz. Sir, you may begin.
Welcome all of you, and thank you for joining us today for our third quarter 2022 results conference call. We hope you've had a chance to review the two press releases we issued earlier today summarizing our accomplishments this quarter and announcing the publication of the results of our phase II-B trial for treatment-resistant depression in the New England Journal of Medicine. Again, my name is Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways, and today I'm joined by George Goldsmith, our Co-founder and Executive Chairman, our Chief Executive Officer, Kabir Nath, Dr. Guy Goodwin, Chief Medical Officer, and Mike Falvey, our Chief Financial Officer. The call is being recorded and will be available on the COMPASS Pathways Investor Relations website shortly after the conclusion of the call.
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. Actually, 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 quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission and in subsequent filings made by COMPASS Pathways 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 as of any subsequent date.
We specifically disclaim any obligation to update or revise any forward-looking statement, even if our estimates or assumptions change. With that, I'll now hand the call over to George Goldsmith.
Thank you, Steve, and welcome everyone. It's with excitement and some sadness that I open this call as my final quarterly results call for COMPASS. I will serve as Executive Chairman through the end of this year to ensure a smooth transition and to continue to serve as chairman of the board thereafter. After my comments, I will hand the baton to Kabir, who will provide the business update. Guy will then cover our clinical progress, and Mike will provide a financial review. After our prepared comments, we will open the call to questions. I am pleased to report that we've made strong progress on our journey to create the future of mental health care. COMPASS has been a leader in developing innovative therapies, combining a powerful investigational drug candidate, psychological support and digital tools.
We're running groundbreaking trials, already delivering promising results for treatment-resistant depression, and we're exploring new indications and avenues where clear patient need exists. We're joining forces with patients, healthcare providers, researchers, and governments so we can forge new pathways to better mental health together. Together we have an enormous opportunity to make a difference in many people's lives. We created COMP360 psilocybin therapy, an investigational drug candidate combined with psychological support that could be developed into a regulatory-approved therapy that patients can rely on and have that therapy reimbursed by insurance. Our groundbreaking phase II-B trial with COMP360 psilocybin therapy in patients suffering with treatment-resistant depression provides a scientific rationale to announce a robust phase III program, which has now had several clinical sites initiated. This phase II-B trial received strong validation through today's publication in The New England Journal of Medicine.
We're honored to have the leading peer-reviewed medical journal publish not once, but twice on COMP360. I want to express my gratitude to those of you who have supported our work or will do so in the future. Everyone has a story. Working together, we can improve the outcomes of these stories. With that, I turn today's program over to Kabir Nath, COMPASS Pathways Chief Executive Officer, who will lead us through today's program. Kabir.
Thank you very much, George, and good day to everyone. It's now been just over three months since I took over as CEO of COMPASS Pathways, and it's certainly been an exhilarating learning experience. Even with my prior exposure to COMPASS through my work at Otsuka, including their investment in the series B round in 2020, I found the level of activity and accomplishment here extraordinarily high, particularly as we finalized the design of our phase III clinical program and presented it to you on October the twelfth during our Capital Markets Day. In that program, we covered not only the phase III design, but also several other important aspects of our work, including our approach to psychological support and digital tools, as well as the advanced work we're already doing to ensure successful commercialization.
I urge you to view the archive of that program if you've not already done so. One of the most striking things in preparing for that presentation was for me to understand the depth and breadth of experience that the executive leadership team here at COMPASS brings to our mission. These qualities, their passion and their commitment to the vision of COMPASS were all evident in the team's presentation on Capital Markets Day. As we look forward to the start this year of our phase III program for patients suffering with treatment-resistant depression, my main priority will be to move COMP360 psilocybin therapy successfully through the clinical trial, regulatory and reimbursement processes. We will also ensure that it's delivered into healthcare systems together with psychological and digital support to patients who urgently need it.
At Otsuka, I'd led the development and commercialization of pharmaceutical products and digital solutions addressing complex mental health needs, and so gained significant experience in integrating pharmaceutical products with digital support. I'm very happy to report that in this really complex area, the COMPASS team is executing very well and focused on the right areas to ensure success. I'm also pleased to report to you that during this quarter, COMPASS continued to make steady progress towards preparations for our phase III program. We've been bringing both experienced and new clinical sites online and also adding to our cohort of trained therapists with very active recruitment and training underway. In the quarter, we also completed the analysis of our phase II- B long-term outcome study, which Guy will share with you in a moment.
Beyond our phase III program in TRD, we have two ongoing COMP360 phase II trials in anorexia nervosa and post-traumatic stress disorder or PTSD. TRD and PTSD represent large patient populations that are underserved by existing treatment options. Anorexia nervosa is also an area of very high unmet need. It has the highest mortality rate of any psychiatric disorder, and to date, no medicines have been approved to treat it. With that, let me now turn to Guy, who will provide his thoughts on the next steps in our planned phase III program and also discuss the phase II-B long-term outcome study. Guy?
Thank you, Kabir, and good day all. Let me begin by reviewing our phase III pivotal program design, the details of which we communicated during our Capital Markets Day presentation, which is available on our website in the investor section. As a high-level overview, we are focused on building an overall data set, which will form the cornerstone of our new drug application with the FDA. We are also looking beyond the approval to launch as well by generating the evidence that we believe will support reimbursement for this novel treatment at scale. Our pivotal phase III trials are designed to answer two important clinical questions. First, can we replicate and reconfirm the compelling treatment response exhibited in our phase II-B trial?
Second, what is the impact of an additional dose on the number of responders and the quality of the response seen in the phase II-B trial? To generate the data that answers these questions, we will conduct two clinical studies. A single-dose monotherapy trial we've named COMP005, and a fixed repeat dose monotherapy trial named COMP006. These designs can answer additional important questions such as, how does the safety profile of COMP360 compare to placebo? How may the response differ between one dose and two doses of 10 mg or 25 mg? We also recognize the need to look at long-term follow-up study that may include elements of durability and retreatment.
Let me point out that the robustness of the phase II-B trial, 233 patients in 22 sites in 10 countries and seven languages, provides us with confidence that we can deliver a successful phase III result. Our phase II-B trial went far beyond the scope of what traditionally have been smaller signal-generating studies. The phase III patient population will also be essentially the same as in our phase II-B trial. That is the same definition of treatment-resistant depression and the same core inclusion and exclusion criteria, which aids in our extrapolation from the phase II-B trial to our phase III trial size and powering. Both of our pivotal studies have a primary endpoint of change from baseline in MADRS total score at week six. The week six endpoint is consistent with previous trials in depression.
We will also be observing the patients at periodic points along the way to the week six endpoint measurements. Providing more detail on the pivotal trials, COMP005 is a single-dose monotherapy trial comparing a 25 mg dose of COMP360 versus a true placebo. Drawing upon the experience with phase II-B and the treatment effect we observe, and taking into account a 2-to-1 randomization to 25 mg, we have determined a trial size of 378 patients. We expect that top-line data from this trial will be available by the end of 2024. The second pivotal trial is the fixed repeat dose monotherapy COMP006 trial with three arms comparing COMP360 doses of 25 mg, 10 mg, and 1 mg. Patients will receive the same dose at day one and at week three.
With the three dosing arms and the two to one to one randomization, we have determined a trial size of 568 patients. Top-line data is expected to be available in mid-2025. The third phase III program trial is a long-term observational follow-up study, the design of which will be influenced by the observations and results of the phase II-B follow-up study, which we announced today in our quarterly results. The 66 patients entering the phase II-B follow-up study were in varying states of response and may not have been fully representative of the main study population. These limitations demand caution so that our conclusions are preliminary and require confirmation in the larger follow-up study we will conduct in phase III. The primary endpoint of this phase II-B follow-up was the median time to a new depressive event.
Depressive events are, for example, initiation of new antidepressant treatment, hospitalization due to depression or suicidality, MADRS worsening, discontinuation for adverse events or lack of efficacy. The time to such an event was longer, 189 days, for the COMP360 25 mg group compared to the COMP360 1 mg group at 21 days and the 10 mg group intermediate at 43 days. The small group in the study that initially responded or remitted with COMP360 25 mg appeared to have durability up to approximately six months. 27% or 40.9% of participants had an adverse event that was ongoing or started after week 12, and a lower proportion of participants started new treatments for depression in the 25 mg and 10 mg arms versus the 1 mg arm.
Suicidality, which is a regrettable risk in this population, was recorded as an adverse event twice in 25 mg group, twice in the 10 mg group, and once in the 1 mg group. These findings also dovetail into our investigation of what a second administration of COMP360 may achieve regarding durability, response, and remission. It will give us additional safety information beyond the more than 500 participants who have been exposed to COMP360 so far. With that overview, Mike, I hand it over to you.
Thank you, Guy. I will now recap our financial results for the three months and nine months ended September 30, 2022. For the three months ended September 30, 2022, net loss was $18.4 million or $0.43 per share, compared with a net loss of $15.8 million or $0.38 per share during the same period in 2021. These results include non-cash share-based compensation of $3.5 million in 2022 and $2.3 million in 2021. For the nine months ended September 30, 2022, net loss was $60.6 million or $1.43 per share, compared with a net loss of $46.1 million or $1.17 per share during the same period in 2021.
These results included non-cash share-based compensation of $9.8 million in 2022 and $5.9 million in 2021. For the three months ended September 30, 2022, R&D expenses were $14 million, compared with $12.2 million during the same period in 2021. The growth was attributable to increased personnel and non-cash share-based compensation costs as a result of hiring to support our digital and clinical programs, in addition to external consulting expenses. This increase was partially offset by a slight decrease in external development expenses attributable to decreased clinical trial expenses, which we expect to increase substantially in the near future as we initiate our phase III program. For the nine months ended September 30, 2022, R&D expenses were $45.3 million, compared with $30.4 million during the same period in 2021.
For the three months ended September 30, 2022, G&A expenses were $11.6 million, compared with $9.6 million during the same period in 2021. This growth was attributable to increased personnel and non-cash share-based compensation costs due to increased headcount, as well as increases in legal and professional fees, facilities costs, and other expenses. For the nine months ended September 30, 2022, G&A expenses were $33 million, compared with $24.5 million during the same period in 2021. COMPASS continues to maintain a strong financial position, with cash and cash equivalents of $173.1 million at September 30, 2022, compared with $273.2 million at December 31, 2021.
The change in cash of $100 million over the first three quarters was due to cash used in operations of $60 million and a change of $40 million due to the impact of exchange rates on our cash balances held in British pounds. We hold our cash balances in dollars, pounds, and euros in proportion to our spending plans in each currency. The pound depreciated significantly against the dollar over the second and third quarters, and as a result, our pound deposits translate into fewer dollars on our financial statements. Since we intend to spend these pound balances rather than exchange them into dollars, the pound's depreciation is not expected to impact our operations or our cash runway, which continues to extend into 2024.
We view our strong balance sheet as an important strategic asset, which we intend to manage carefully as we invest to advance these promising potential therapies, while at the same time continuing to create value for our shareholders. Thank you, and I'll now turn the call back to Kabir.
Thank you, Mike. In closing, we're excited to be moving into phase III with our core program for COMP360 psilocybin therapy in treatment-resistant depression. We've shown you that we have a robust comprehensive program which will answer key strategic questions around durability and the value of retreatment, and which builds on the compelling data we demonstrated in phase II-B. We're confident that these answers will support both the COMP360 psilocybin therapy regulatory approval, but also provide the evidence needed by payers to reimburse this new therapy upon launch. This strategy is highly differentiating in our area of science and will lead to significant value creation over time. In our Capital Markets Day presentation, which I remind you is archived on our website in the investor section, we offered views into aspects of our business that have not been covered in depth previously.
Specifically, we spoke about our commercial strategy and the extensive work underway to prepare for a COMP360 launch. Plus our advanced digital initiatives and the innovative tools which support safety and optimize the experience for patients and provide support, rigor, and consistency for therapists. As George has often said, and as I will continue to reinforce, our goal here at COMPASS is to turn our vision of building the future of mental health care into a reality. As we enter the final stage of pivotal development in TRD, our sights are set on achieving this goal, improving patient outcomes and creating value for health systems by combining our medicine with psychological support and digital innovation. We'll now open the line for questions. Operator, please.
Thank you. As a reminder, to ask a question, you'll need to press star one one on your phone. Please stand by as we compile the Q&A roster. One moment for our first question. Our first question will come from Charles Duncan of Cantor Fitzgerald. Your line is open.
Yeah, super. Thank you, George and team, Kabir, for taking our question, and congratulations on the New England Journal publication. Very, very good to see. Had a couple of questions on the pipeline, obviously. With regard to the long-term observational study that you mentioned for phase III, is that needed to be complete before an NDA is filed? And if not, could you help us understand when filing could happen after the other two phase IIIs? And then for Guy, you read through pretty quickly. I just wanna check that yeah, time to depressive events for 25 mg was, like, 189 days, and I think you said 21 days for the 1 mg. You changed the order a little bit.
Thank you, Charles. Let me ask Guy just to fix that second point first, and then I'll come back to your first question.
Yes. Thank you, Charlie. You heard correctly that the difference between the 1 mg and the 25 mg was 180 versus 21 days. Yeah.
In terms of the first question, obviously it's a bit premature to speculate on our overall regulatory strategy right now, but we view COMP005 and COMP006 as the pivotal trials from a regulatory perspective. You know, typically the observational follow-up would indeed be that. Clearly, it's very important to continue to monitor for new safety events in particular, but you should regard the pivotal package as COMP005 and COMP006. That should be the base case.
Okay, just one clarification, if I may, with regard to the phase II-B long-term observational. I guess I'm wondering if the patients that enrolled or rolled over to the OLE were equally representative in the three groups? If you can provide a little bit of color on that, when would you anticipate presenting the data? This is very interesting.
Well, quite simply, they didn't have the same response rates as the whole population at three weeks. There was certainly some unrepresentativeness in the patients rolling over, shall we say.
Yeah.
Of course, the numbers give us relatively small numbers in each cell. We're going to be kind of very keen not to overinterpret our data. We think the field has too much of that already.
Yeah.
I think the way we publish this, we'll be cautious. You know, it's sort of supportive overall of the main finding, but it's limited in how far it adds to what that main finding.
I got it. Really more definitive with the phase III program.
The phase III program will have the numbers and the incentives for patients to join this trial, which I think will be important for getting a really representative group of patients on whom we can base really important plans about how to deliver this treatment in practice with pretreatment, et cetera.
Very good. Last question. COMP005 in terms of time to data end of 2024. I guess I'm wondering if you could provide us some thoughts on what is really governing that time. Could it prove to be overly conservative?
We certainly hope so. I, you know, we're very much in the hands of others in this regard. We think we have a realistic and conservative plan. Of course, if it delivers before that actual time that we've given, we'll be delighted.
Well, I'm sorry, is it enrollment or is it therapist availability or something outside of, say, the patient population?
I mean, we can't really say what will be limiting in any individual site. You know, the overall rate of recruitment, we believe will be satisfactory to deliver on the time that we've given.
Very good. Thanks for taking my questions.
Thanks, Chad.
Thank you. One moment please for our next question. Our next question will come from Neena Bitritto-Garg of Citi. Your line is open.
Hey, guys, thanks for taking my question. Just another follow-up question on the phase II-B long-term data that you talked about earlier. I know, Guy, you mentioned that in the small group of initial responders or remitters, durability appeared to be sustained out to six months. I guess can you just define what exactly you mean there? Like what proportion of the patients who were responders and remitters at week three were actually able to sustain that response out to six months? Just a question on the New England Journal of Medicine publication. I noticed that it looked like patients who had higher severity on HAM-D-17 at baseline performed pretty similarly on change from baseline and MADRS versus those who had less severe disease at baseline. I'm just curious if that's kind of consistent with what you had expected. Thanks.
If I could take the second question first. You make an interesting point, and there are many trials that people try to rescue by making a cut with the higher severity illness versus the lower. We were very pleased to see that there was really no difference between the two, the severe and the moderate groups. We thought that was a big plus. It's not what you always see with other trials in this area, particularly in MDD. We are of course in treatment-resistant depression and that does change the perspective and expectations a bit. Overall it was very gratifying to see equality of effect, and good news for the patients who fall into the two groups, of course. I think the issue is about the numbers. The numbers are small.
We aren't at this stage publishing them in great detail. It's really not possible to say how many of the patients, because of the relative stratification of the rollover. We're not confident that we have an absolutely representative group in the 25 mgsixgoing into the follow-up. Those who did continue to remain with scores which were either half of the original baseline score, which is definition of response or in remission up to the 6-month period from the dosing. I think we can say that of the patients we observed who had responded and remitted and showed stable response and remission at 12 weeks, they continued to show that remission up to six months in the 25 mg group.
It's a very small numbers, and beyond that point, we lose people from the study for various reasons, you know, that just happens that it's very hard to keep people in the study with relative little incentive. And therefore we end up with very, very small numbers. Beyond six months, we can't really make a meaningful statement.
Okay. No, that's super helpful. Can you just remind us to how many people actually entered the open-label extension for the extension period?
666. It's about 20 in each of the three categories. Well, actually no, it was 66, but that included patients from COMP003. The COMP003, which was the study with SSRIs, if you recall. That they included a few patients in that group. We were looking at between about 19 patients in each of the cells, as I recall. You know that's getting to numbers that although others have made a big deal of outcomes for those numbers, we're really reluctant to do so.
Got it. Okay, that's helpful. Thank you.
Thanks, Neena.
Thank you. One moment please for our next question. Next we have Ritu Baral of Cowen. Your line is open.
Good morning, everyone. Thanks for taking the question. Guy, forgive me, I've got a quick follow-up to Neena's question again just on these figures and the idea that these are not representative patients. Is your comment on the representativeness based mainly on the response rate to the treatment seen in the blinded portion? Or is it a function of sort of as you look at the baseline of these patients versus the overall baseline of everybody heading in that makes you believe it's not representative?
It's entirely based on the response rates.
Got it.
We're just concerned that we don't have. You know, obviously, they are themselves. They were eligible patients, you know. There's nothing wrong with them as patients within the group. It's just that as a group, their composition is a little unlike the actual composition of the 233 patients in the blinded phase of the trial.
Uh-
It's just the extrapolation is a little tricky. You know, when you have 19 patients, as I say, we-
Right.
We just feel that's a bit small, really.
It will introduce some bias. Okay. Got it. That makes sense. On the phase III program, has FDA mentioned anything about a requirement for treatment in patients on background SSRIs, as part of the phase IIIs? Will those be allowed in the long-term follow-up, or is there a proportion of patients or a cohort that you might allow in COMP005 or COMP006?
Not in COMP005 and COMP006. We're close to finalizing on the long-term follow-up, but we'll announce that in due course.
Got it. Just in terms of COMP006, the six repeat dose study, you know, how should we be thinking of what that top-line data will show with the two doses? Right now in the body of evidence that you guys have seen and in the granularity, do you expect, I guess, better three-week or six-week efficacy rates? Or do you believe that double dose and double treatment rather, it will have more of an effect on durability?
Well, it's a good question, and it's the reason we're doing the work. I think we can have a hypothesis, which is that we will see higher rates of remission after two treatments, particularly at 25 mg. It'll be very interesting. We simply don't know about the 10 mg. That's why we're doing the study. Durability, yeah, we'd be delighted if it turns out to be the case, but, you know, we don't have a hard and fast prediction on that.
Got it. Thanks for taking all the questions.
Pleasure.
Thanks, Ritu.
Thank you. One moment for our next question. The next question will come from Patrick Trucchio of H.C. Wainwright & Co. Your line is open.
Hi. Good morning. I have a follow-up question on the phase III COMP360 program in TRD. I think one of the changes for the phase III from the phase II is the need for one person to provide psychological support rather than two. I'm wondering if, you know, first can you confirm that change? Can you discuss the implications of the change, including the regulatory input received regarding it and how it would be expected to impact the phase III program and eventual commercialization?
Thank you, Patrick. This is Kabir Nath. Let me take that. Yes, we can confirm that for the administration session, there will only be one person, one therapist required to be present. I think, you know, without going into great detail around our regulatory strategy, clearly, you know, it is not our intent to ask the FDA to regulate psychological support. That's not their role. Their role is to regulate drug therapy. Therefore, there is, you know, discretion to some degree around how psychological support is provided, though clearly that again is, you know, something that needs to be aligned as appropriate. From the point of view of how we think about that going forward, I think it's important to recognize that a trial setting is clearly different from a potential commercial setting.
You know, in a trial setting, we are having to prepare patients for the possibility of different doses. There's a very different set of preparation and expectation that's required for that. We are already working through some of the ways in which that may change when we actually get to commercialization. As we talked about on October the twelfth as well, we are looking at ways in which we can look at different ways of optimizing psychological support, working with what are likely to be some of the commercial sites of treatments such as the chains of clinics, ketamine clinics and so on that we referred to at that time. There will be work in parallel with the phase III to look at how we actually do optimize the psychological support piece as well.
Can I add, Patrick, that I think it's also key, and it's not sometimes appreciated, that the psychological support is offered equally across the three or the two arms of the study? Any differences we observe are clearly attributable to the drug. I think sometimes there's a certain amount of confusion about that. Irrespective of what the psychological support is, it's equal across the three arms, and the differences that emerge in the trial are due to the drug differences.
Right. That's helpful. Just a follow-up on the therapist for the phase III TRD program. I'm wondering if you could provide some insight into the training process for the therapist participating in the phase III program. You know, is this consistent with you know, what has been you know, kind of previously published around the COMP360 protocol, or do they have to complete a certain amount of training or is it maybe, I don't know, is it streamlined from that? And is there any prior experience you know, administering psychedelic medicines required? And how quickly you know, would you anticipate this ramp up progressing you know, to ensure you can enroll the studies on schedule?
Just finally, would there be expected to be sort of a synergy or benefit from the training of these therapists who could then perhaps participate in, you know, other COMP360 trials such as those, you know, looking at other indications like PTSD, anorexia, et cetera?
Yeah. Patrick, let me try and take those elements in sequence. First, the training is similar to what we provided in the phase II-B, but we have streamlined it, and in particular, a lot more of it is delivered online. Therapist Companion, which is the app that is designed to work with therapists, enables us to deliver significant amounts of that online. But yes, there is still a tailored training requirement for therapists to participate in the phase III trial. In terms of the recruitment of therapists, the way we do it is we clearly identify sites and the sites themselves. One of the criteria is that the sites themselves have competent therapists that they are used to working with, and they nominate the therapists. They then go through a qualification process with us, followed by the training.
You know, for phase II-B, we used around 65 therapists. For phase III, we will need to use somewhere in the order of 250. As mentioned in the prepared remarks, we're already well underway with actually interviewing those that have been identified by new sites and training them. I actually do not see that as any sort of barrier in terms of getting recruitment in place. I think we're confident of that from a therapy perspective. Yes, we would envisage the same therapist potentially being able to support other indications, though recognize that particularly for anorexia, there is likely to be some different training content. It is a very different disease from treatment-resistant depression.
You know, I think the final thing I'd just say is clearly, you know, the cohort of trainers in phase III will be the nucleus of what could be, you know, the commercial cohort. Also we are looking to identify, you know, train the trainers and mentors among these who can actually help us then build scale in the therapy network.
Yep. That's really helpful. Thank you so much.
Thank you, Patrick.
Thank you. One moment for our next question. Our next question will come from François Brisebois of Oppenheimer. Your line is open.
Hi. Thanks for taking the question. Just one here on, I guess to start. In terms of going from a, you know, one-make placebo equivalent to a real placebo, I was just wondering, obviously in terms of the effect, there shouldn't be much there. Do you anticipate, you know, how do you deal with patients not, you know, at this point knowing that they might not have anything at all versus, you know, in a trial where the one-make placebo ensures that patients know that at least they're getting some psilocybin?
Yeah, thank you. You make a very good point. I think that the dilemma is that the only way to establish a true safety baseline is to use placebo. Obviously the patient experience is something that we're going to try and understand, and we're gonna look at expectations and just how that relates to outcomes. Obviously placebo is not without an effect in depression, and in fact, it is often a big problem in depression trial, to put it mildly. We expect that the whole experience, the the multiple visits, the long time in a pleasant environment, even the introspection, which we know that some people actually find very immersive, is not without an impact. We will be interested to see what happens.
It's worth saying that some people who get 25 mg actually don't get much of an effect either. You know, it's not a completely cut and dried, but it's clearly, as you're indicating, it's more different than in the case of a 1 mg versus 25 mg. It's really the only way we can do the necessary safety baseline.
Okay. No, that's helpful. Then in terms of the new space, just to add on a little bit to Charles' question, maybe in terms of barriers to enrollment, like, you know, any trial has sometimes. Have you ever run into the issue with sites or PIs from sites or certain therapists that just there's a different, you know, thought process because this is so new between believer sites maybe or more skeptical sites in terms of your enrollment? Or has a lot of maybe the initial skeptics post the phase II-B data, are actually, you know, probably more excited now to join the study? Just thinking enrollment here. Thank you.
I mean, we have some very enthusiastic sites. If you watched the Capital Markets Day, you will have seen Sidney Zisook, who is, you know, an example of that. I don't think we are looking for not excited sites, to be absolutely honest. I mean, we want people who will be keen to recruit. I think that we had a proper skepticism in the original PI group. I haven't heard any of them push back on our interpretation of the findings, and they have, you know, been happy to be co-authors, as you will have noticed, all of the people who contributed materially to the study were co-authors in the New England Journal paper.
I think we have a very solid basis of understanding to move forward through to other sites, to sites who will get this educational input from us about the experience and about the outcomes from phase II. I don't think we should worry too much about this. I think it's not going to prove to be a major issue.
No. Thank you, Guy. The only thing I'd add, just to remind you, is that it's also important that we actually work with lots of sites that do not have experience in psychedelics. It's really important from a generalizability that we see that. You know, we have, again, as in phase II- B, we are ensuring that the number of patients with prior experience is capped at a low number. But it's also important that, you know, for generalizability, we also have sites that don't necessarily have psychedelic experience beforehand. To build on Guy's point, we do not see this as any sort of gating item in the recruitment process.
Understood. Just lastly, in terms of the filing and on the regulatory side, you mentioned, you know, that you consider the two phase IIIs, not the extension, to be pivotal. At the same time, I was just wondering, in terms of the outcomes, a lot of learnings from the repeat dose, is there an angle where one might be more important than the other to be positive? Could you know, ultimately, can you file with only one positive outcome or do you need both? Thank you.
It's a fair question, Brad, but again, I mean, I think as Guy answered to an earlier question, we have to run the trials. You know, we can't answer that question in the abstract. We have designed a program that we think between these two trials answers key questions around, you know, what does a repeat dose do perhaps in terms of efficacy and durability as well as the pure placebo comparison from a safety perspective. Honestly and truly, you know, until we've run both the trials and seen the data and, you know, discussed with the FDA, that would be a review issue.
Okay. Thank you, and congrats on the publication.
Thank you.
Thanks.
Thank you. One moment for our next question. The next question will come from Bert Hazlett of BTIG. Your line is open.
Yes, thank you for taking the question, and my congratulations as well on the publication. Just coming back to one element of the time to event analysis and the follow-up, the phase II-B follow-up. I guess it's focusing more on reimbursement in general, taking a step back. Is that magnitude of data or that magnitude of difference should you replicate that, is that something based on your discussions with payers and as you think about reimbursement, is that something that should be sufficient to support a level of reimbursement you were thinking about with this program?
Thank you, Bert. That's a really good question. I think a couple of points. I mean, while we've clearly had a number of discussions with payers around our overall strategy and so on, you know, we have not yet advanced to the point of that sort of level of detail discussion of really, you know, talking our value models in detail, let alone actually putting a price into them to discuss with payers. It's somewhat early for that. I think, you know, as Guy has said, we would be wary of reading too much into COMP004 as an evidence base.
You know, I think with what we are designing in COMP005 and COMP006 and the fact that there will be, you know, available at the time of talking to payers, some data from COMP007, from the long-term observational. I'm confident that we will have enough data for the basis of those discussions. I wouldn't say that we have it yet.
That's helpful. So would you consider then this type of data central to that discussion, or is it maybe more of a focus on remission? Or could you just give maybe a little bit more about how you're thinking about building in a reimbursement argument, if you will, into the phase III program?
I think the first place we would start is, you know, simply the efficacy and safety of either even a single dose or potentially repeat dose relative to anything else that is available for patients with treatment-resistant depression. I think, you know, at first base, we have a very compelling traditional value argument around the benefit we bring in treatment-resistant depression. I think that, you know, as we get closer, as we actually see the data from COMP005 and COMP006, thinking about how we might explore more innovative discussions around reimbursement, around the potential of treating to remission and what that looks like from a value perspective, those are certainly all options. You know, candidly, until we've generated the initial data, it's premature to talk about what that strategy might be.
Terrific. Thank you for that. Just one more quick one. Not sure whether I missed the potential timing of the readouts for phase II in PTSD and anorexia nervosa. If there's any guidance there, that would be helpful.
In the latter part of next year.
Okay.
Late 2023.
Thank you very much. Congrats again.
Thank you. One moment for the next question. Our next question will come from Esther Hong of Loop Capital. Your line is open.
Hi, good morning. Thanks for taking my questions. I wanted to know first, how did the long-term data inform the repeat dosing study, COMP006. A clarification on how many days out for the 10 mg. I know there's about 189 for the 25 mg and 21 for the 1 mg. I've got a follow-up on training. Thanks.
Okay. Well, the intermediate number was about 50 days for the 10 mg, if you want to compare it with the 21 and the 180. It was intermediate. In a sense what this is reflecting is the pattern of response in the first 12 weeks, as you can kind of see. Sorry, what was your first question?
How did this data inform the repeat dosing study?
Yeah. Okay. I'm not sure that it fully informed it, really. I mean, the repeat dose study was really based on our considerations of the 12-week data and the full data set. I mean, this follow-up element, as you've heard me say, is something that we are not taking as being very definitive, but simply supportive of what we had already concluded from the phase II-B 12-week study.
Just as a follow-up, these patients will have placebo, which is, you know, probably as Kabir said, the best measurement. In the real world, do clinicians wanna see practicing prescribers, do they wanna see the potential to how this is used with SSRIs or antidepressants in combination just to have that antidepressant as a backstop? Will they wanna see more data like the study that you previously conducted?
Well, knowing clinicians, the simple answer is yes.
Okay.
Yeah. Esther, just to build on that. I mean, it is a great question. I mean, we have deliberately made the choice here, as we said earlier, that these are monotherapy trials. We think that is still needed in order to truly demonstrate the efficacy and safety of COMP360 psilocybin therapy. You know, we do not intend to run a significant adjunct program as a randomized trial. As Guy says, we recognize the reality of what use will be. Again, you can expect us over the next few years in parallel with the randomized trials to be looking at real world studies and other things that may actually help to answer that question. Yeah, we recognize the reality of real world use.
Got it. Then just to follow up on Patrick's question on training. MAPS will have their phase III program completed pretty soon for MDMA for PTSD. Was wondering if there's overlap between training therapists for that program from MAPS' MDMA and COMPASS's COMP360, such that, you know, there are potentially more therapists than each of these sponsors have trained. Thanks.
I can't comment on how MAPS is going about choosing or training therapists, honestly, 'cause I actually don't know. You know, we are very focused, as I say, on the sites we work with. They actually nominate therapists. We then go through that process ourselves, of assessing and training them. I think, you know, the broader picture is, you know, in the long run, we hope and believe that a number of these different molecules will end up being successfully approved for a number of different diseases and so on. Is it feasible that there is tailored training for each molecule, for each indication? Almost certainly not.
I think again, as this space continues to evolve, as other companies advance, you know, to phase III and beyond as we have, then I think you will see this evolve. Right now, we're focused on the therapists required for our programs, and we're doing that, you know, on our own.
Great. Thank you.
Thanks, Esther.
Thank you. One moment please for our next question. The next question will come from Sumant Kulkarni of Canaccord Genuity. Your line is open.
Hi. It's nice to see a publication, and thanks for taking my questions. I have two, both on the COMP360 phase III design. First, do you expect to conduct an interim analysis on your COMP005 phase III trial?
We don't expect to, no.
Thanks. Second, at this time, we know you've chosen a fixed repeat dose trial. That's COMP006, with a relatively short time between the first and the second dose. Either in your internal deliberations or those with the FDA, did this design compete at all with an as needed repeat dose design over the course of a year, for example, which would be somewhat similar to Sage's LANDSCAPE program on zuranolone. That's a non-psychedelic compound obviously for MDD, but has some commonality in that it has elements of episodic therapy for a condition that's currently treated chronically.
Yeah. It's a good question, so I mean, I think, you know, recognize that we're still at the relatively early stages of demonstrating the profile of COMP360. The decision here was that let's answer, you know, the question that came up repeatedly after phase II-B, which is what is the effect of a repeat dose. Really that's what we've set out to answer in COMP006, both from Kenneth, you know. As we said, it asked an earlier question, can it enhance either efficacy or durability, particularly what might two 10s do, given that 10mg was not an effective dose in the phase II-B.
Great. I'll squeeze one in on the anorexia trial. Do you think the EDE scale is sensitive enough to pick up differences in maybe diet conditions post-dosing? Because this is such a different kind of treatment paradigm compared to the typical dosing paradigm, I would guess, in anorexia.
Yeah, that's a great question, and we've been concerned about that. I mean, it is the scale that has been used in psychotherapy trials. You know, obviously you start with where the light is. We've added sort of clinical global impression, which is kind of something that will grow out of a detailed analysis of the EDE. If someone conducts an EDE, then they will have a good way, a good basis for making a clinical global impression. Actually, we started on a program because if we're in phase II, obviously a certain amount of experimentation is permissible. We started looking at how we should actually develop scales for phase III program. You know, you're absolutely right to highlight this and we're on it.
Thank you.
Thank you. One moment for the next question. The next question will come from Jason McCarthy of Maxim Group. Your line is open.
Hey, guys. This is Michael Okunewitch on the line for Jason. Thank you for taking the questions. I guess the first one, I'd just like to ask, the bifurcated phase III program. I'd be interested to see your initial thoughts on how it might work out for labeling and for commercial use in a scenario where you have improved efficacy on the dual dose, but it's still significant on the single dose. Would you expect this to result in perhaps two different approved protocols? And would you be looking at any potential digital biomarkers to kind of predict which patients would be likely to benefit from that repeat dose?
It's a great question. You know, I think again, we clearly are at only the early stages of determining what our ultimate regulatory strategy would be. You could certainly envisage a relatively broad label for the treatment of treatment-resistant depression with the different studies in the label. Because I think, and I'll ask Guy to comment after this, our expectation is that psychiatrists would want significant flexibility about how they think around dosing and so on. In terms of the digital part, absolutely. In the future, we clearly see that, and we spoke a little about that at our Capital Markets Day. To be clear, in the phase III, we'll be testing many of our hypotheses in terms of collecting digital markers from patients through the MyPathfinder app, subject to patient consent, of course.
We will actually be using the phase III data to test many of those hypotheses. I would not envisage that at launch we would necessarily have the digital support to indicate which patient might fall into a single dose or a repeat dosing category. In the long run, that is certainly part of our aspiration.
I think I would add that, you know, we're going to also learn from the patient experience, from whether or not one or two is preferable and that will be invaluable in thinking about the commercial role.
All right. Thank you. Just, as a follow-up, given what you saw in the open label extension with the times of depressive event of around six months, are there any thoughts towards running a study to evaluate long-term repeat dosing, such as, you know, dosing after a relapse, possibly as a post-marketing study to maybe support with reimbursement?
I think that's a great question. You know, again, I'll be candid. Right now, we've been focused on the pivotal programs. We know that they will answer some of the questions, but by no means all the questions. The long-term follow-up of these two will perhaps enable us to answer some of that what you've asked. You know, I would expect that you would see, you know, whether it's COMPASS-sponsored post-marketing trials or other potential trials, real-world trials that actually attempt to answer questions like that around, you know, treat to remission or, you know, repeat at some point. Again, to build on your earlier question, clearly having digital markers available would be, you know, both very relevant and very helpful to treatment-resistant depression around that.
All right. Thank you very much. I really appreciate the additional clarity.
Thank you.
Thank you. I see no further questions in the queue. I would now like to turn the conference back to management for closing remarks.
Thank you very much, everyone. Thank you for the questions today. I think again, this is a very big day for us with the publication in the New England Journal, which we're incredibly proud of. Reiterate the fact that we are excited that we are entering now the final phase of development for treatment-resistant depression. We have lots of opportunity to make a serious difference in outcomes for patients with serious mental illness. Thank you for your support. Have a good day, everyone.
This concludes today's conference call. Thank you all for participating. You may now disconnect and have a pleasant day.