Welcome, everyone. Thanks for joining us. This is Gavin Clark-Gartner with the Evercore ISI Biotech Research Team. I'm really happy to be here with the Compass Pathways team. So we have Kabir Nath, who is the CEO, and Dr. Steven Levine, who is the SVP of Patient Access and Medical Affairs.
You got it.
Great. Thanks for joining us, guys.
Thanks, Gavin.
Definitely. All right, so maybe just kind of level set and open us up here. Why don't you give an overview of the company, where things stand today?
Sure. So compass Pathways is a biotechnology company that is focused currently on developing a synthetic formulation of psilocybin for serious mental illness. We have a robust Phase III program in treatment-resistant depression, consisting of two Phase III studies that are now underway, and on track for a readout for the first study, which we call 005, in the summer of 2024, and the second study in 2025. We also have two Phase II studies going on, a safety study, open label in PTSD, where we will see safety top line at the end of this year, and a Phase II controlled trial in anorexia nervosa, for which, we have not given guidance on data, but that's a 60-patient trial.
In parallel, we're doing the work to really start to establish some proof points around the commercial potential for psilocybin in treatment-resistant disease and depression, and Steve can perhaps comment on some of the work we've done there.
You know, recognizing that what we're developing is potentially a new paradigm in the approach to the treatment of these conditions, we've thought early about what are some of the required elements to ensure that should we receive regulatory approval, we also achieve broad and equitable patient access. So that includes a lot of early work in understanding sites of care delivery and where this treatment may be delivered. Some of that is influenced by what we've seen develop in the market so far with existing treatments that have already been approved that have more complex delivery, such as esketamine.
We've also thought a lot about what we required as far as reimbursement, and not just the pricing of the drug itself, but the recognition that as a treatment that requires a delivery within a center with the support of a therapist in the room to ensure that there is coding in place to make sure that those providers are reimbursed for their services. And to that end, we spent the past few years developing an application for a new Category III CPT code. We collaborated on this with the MAPS Public Benefit Corporation, and that code was accepted and goes live on January 1st, and really is an important milestone in creating the framework to make sure that reimbursement is in place at the time of launch.
Additionally, we've done other early work in developing some models that we'll be able to discuss with payers as far as demonstrating the value of our therapy, and some of the other work related to supply chain and ultimate commercialization.
Yeah, that's a great overview. Obviously, much of the focus has been on depression, maybe rightfully so, but maybe we could actually start off on the other side with anorexia nervosa. Can you just kind of give us a introduction to this indication, why COMP360 should be applicable, and then we'll kind of talk through the trial design.
Sure. No, happy to do that. So, part of Compass's strategy has been to support a number of investigator-initiated studies to see if there were signals generated in a range of these really hard-to-treat diseases. As a reminder, there is no drug today approved for anorexia nervosa. It is the serious mental illness with the highest rate of mortality of any, and, you know, really a devastating disease for which there are very few solutions today. We had supported an investigator-initiated study at UCSD with Dr. Walter Kaye, and also another study at Imperial College London, and what we saw from that, open label, small numbers, though, was a real signal of potential for change in these patients with this disease.
There is actually no real validated endpoint for anorexia because there has never been a successful study, but we use the Eating Disorder Examination, which is a complex physician-administered questionnaire, which really assesses where somebody sits on a scale relative to the norms around certain attitudes to food. So based on what we saw as very positive signals, we thought it would be, you know, really important to see whether we could actually develop a more robust proof of concept. So the study we're running, it is a 60-patient randomized trial across, now I think it's at six sites now altogether across the U.S. and Europe. And again, a single dose of 25 milligrams psilocybin against a control dose. Anorexia, let's also remember, unfortunately, is a disease in which patients are typically not motivated to seek treatment. In fact, they actively resist treatment in many cases.
So as we've acknowledged publicly, it has been challenging to recruit patients into that randomized trial, but that's what we are now doing. And again, you know, this is clearly we're going slow. This is an adult population. It's not the sickest population. It's nobody under age eighteen. But again, I think we feel that it's really, really important to do this hard science to see if we can deliver something that could be a promise for these patients.
Yeah, that's a great overview. Maybe we'll jump over to PTSD also. Believe there's still some data on track for end of this year, so maybe you could just frame expectations for this.
Sure. Steve?
Yeah, so the PTSD study is a smaller 20-patient study. It's largely safety and tolerability focused, and we anticipate having the safety tolerability data by the end of this year. There is an efficacy endpoint, though, the CAPS-5, and that data will follow a bit later, at the completion of 12 weeks. And, you know, the focus initially with safety and tolerability is the recognition that in this population there's certain vulnerabilities, given the nature of the illness and the fact that these patients have experienced trauma. And, you know, the question that we needed to answer initially of whether a psychedelic experience would be provocative of a particularly challenging experience for them.
And so, you know, we look forward to being able to provide more guidance on what we've seen as far as safety and tolerability in the very near future.
That makes sense. For PTSD, just thinking about it more from a commercial and a delivery perspective, there'd presumably be much more overlap with depression, maybe compared to anorexia.
That's exactly right. In terms of the comorbidity of the two illnesses, as well as the settings of care in which those patients are treated, you're right, there is a lot of overlap with the major depressive disorder, treatment-resistant depression population, and PTSD. Those with anorexia nervosa tend to be treated in more specialized settings.
That makes sense. All right, so jumping over to, depression then, maybe you could just quickly give us a recap of the Phase III trial designs.
Sure, happy to do that. So two trials, the first trial we call 005, and this is a two-arm trial, single dose of 25 milligrams of psilocybin against true placebo. Both studies run for 52 weeks with a similar design across three phases. Part A, which is to the primary endpoint at six weeks, which is going to be difference in change from baseline MADRS from between the arms. A further six to 26 weeks, which we call Part B, and in that, for patients who have either not responded or who remitted and then relapsed, they have the option of a further dose of their original assigned drug. So this is fully randomized in the original lanes for 26 weeks.
And then from week 26, 26 weeks of open label to 52 weeks, in which every patient has the opportunity to get a dose of 25 milligrams. So that was really the incentive to pull people all the way through the long-term follow-up. So first study, placebo against single dose of 25 milligrams. So really replicating the data on efficacy for 25 milligrams, getting a true safety baseline for psilocybin, and also generating data on durability, the potential for repeat, and a sense of what a typical durability or range of repeat might be. In the second study, we're using the same three doses that we used in the Phase IIb of 1 milligram, 10 milligram, and 25 milligram. A reminder that this is an overwhelmingly psychedelically naive population. In the Phase IIb, it was around 94% naive.
In the Phase III, recognizing the greater experiences out there in the world, we are capping previous experience to 15%, and it may actually trend a little lower than that. The importance of that is for people who have truly had no experience, being told they are going to get an active dose, we believe it's actually really is functionally blinded, even between the one, the 10, and the 25, because there's a wide range of inter-subject variability on response to a psychedelic dose. In this study, the key thing we're studying is the effect of a second dose, a repeated dose. This is a dose at baseline and a repeat dose at a fixed interval of three weeks, again, with the same primary endpoint at six weeks.
The reason for this is, as we discuss the results of the Phase IIb with investigators, with providers, what we saw as a readout in the IIb was roughly a 37% response rate to the 25 milligram, and then roughly 22%-25% sustained in remission through 12 weeks. The belief that a second dose may actually increase some of those parameters, either in terms of response, depth of response, or durability of response, and that's really the key set of hypotheses we're testing in 006. Similar design, six-week primary endpoint, six-26 weeks in the same blinded, randomized assignment with the option for another dose if they have not responded or if they remit and then relapse. Then again, 26 weeks open label, running all the way to 52 weeks, with the option for a further dose, again, to incentivize people through.
So taken together, we believe this is a pretty robust package, which will first demonstrate efficacy and safety for one or two doses, give us some really good data on durability of one or two doses, and what the range of requirements for repeat is for patients, and indeed, what the efficacy of repeat is. And then also, I think in the open label section, when a number of patients will be back on antidepressants, because obviously, in this population at some point, you need to allow them. I think some very interesting evidence that is really relevant to the real world around adjunct. As a reminder, both these studies are monotherapy. Patients are required to be washed out on entering the study.
Great overview. Maybe just a last question before touching on the commercial side of things. One of the potential risks, just inherent in depression trials and with this model is as you expand to Phase IIIs and expand the number of sites, you may, you know, potentially lose control over some characteristics of the trial, right? Whether that is baseline characteristics kind of looking different and the, you know, screen fail rates different, whether it's, you know, just general patient commitment to the therapy. Is it, maybe you could help us understand... I should also mention specifically, rescue therapy use could also be a key consideration. Maybe you could help us understand some of the measures you've taken within the protocol formally and maybe outside of the protocol to control that?
... Sure. No, and it's a great question. You know, Phase 2-3 in psychiatry is always a challenging bridge or hurdle. So, a couple of things. First, I think the patient population is the same. So, you know, we, you know, sometimes you see changes or whatever, this is exactly the same patient population from IIb to three, same inclusion, exclusion criteria. Second thing I would say is our IIb was by the standards of neuropsych, Phase IIs, large and robust. 233 patients, 10 countries, 22 sites. So already a mix of sites that went beyond the typical, you know, very contained academic sites that people use. So I think, again, that contributes towards risk mitigation.
But third, I mean, I think, you know, everything else falls into the general bucket of execution, and you are absolutely right that a laser focus on execution is really, really important. What does that mean? You know, we really are being very robust on these inclusion criteria. The two to four documented failures of specific medications in the current episode of treatment. Not always easy to get to those records, but we are being very, very strict around that. We were on the IIb as well; we will continue to be here. Obviously, we do have more sites. You know, we've gone from 22 sites to something that will be closer to 100 sites across these two studies, but being very selective about those. Again, it's a mixture of academic sites.
There are a handful of commercial trial sites, but there are other sites that we believe could move from being, you know, today, academic centers to potentially large sources of patients in the future. But yeah, this is, you know, where we're spending most of our effort around execution, around managing these execution risks. You know, there will be sites that roll out of the study if we're not happy with performance or rate of recruitment and so on. And yeah, I think it's fair to say we've assembled a team that is acutely conscious of some of these risks, has experience in psychiatry trials and, yeah, very focused on that.
I think that's well said. Turning over to the commercial side of things, and maybe it's a question for Steve, is just kind of give us a framework for number of... however you want to lay it out, whether it's number of depression patients, number of, practices or providers that have, you know, some of the basic infrastructure and capabilities to deliver this type of therapy, notwithstanding some of the specific economics, which, as you laid out, will kind of become more clear the next couple of years.
Yeah, great question. You know, first of all, you know, sadly, there are lots and lots of patients who are currently not well-served with existing options, and they are all over the country, right? They're not just concentrated in one area or one type of site. And so, you know, with that, I think one of the bigger initial questions is, where are these patients currently receiving their care? And who is most ready to potentially deliver a therapy that has the components of COMP360 treatment? And those sites that don't currently have that infrastructure in place, what it would take to get there. Those that currently have it in place, though, are likely the sites that already deliver interventional psychiatry. That would include TMS, transcranial magnetic stimulation, esketamine, ketamine, et cetera.
They largely already have the infrastructure in place to be able to manage the administrative and operational complexities of a treatment like COMP360. They're used to contracting with payers, to ordering and storing in a compliant way, a controlled substance, complying with the terms of a REMS, managing the patient flows, and the team-based workforce of an interventional treatment. And to date, you know, there were probably 400-500 interventional sites across the country that exist. When you add on hospital systems, regional health systems, integrated delivery networks that also deliver high volumes of interventional care today, there's already a fairly robust infrastructure that is fairly well prepared at this point to be able to deliver our treatment, if approved.
Beyond that, you know, there are other smaller practices that also are, you know, widely contracted with payers, with an emphasis on access, that also have multidisciplinary teams already within their centers. And we'll be working to figure out what kind of additional activation services they may need, what kind of support they may need as we approach an approval and launch as well, to make sure that across the diversity of sites where patients currently receive their care, we can enable access as much as possible.
Yeah. And are you guys essentially building out a best practices book for some of those other sites to just kind of give them the playbook so they can onboard really quickly in the future?
You know, I think some of that will emerge over time. As Kabir said, some of our existing clinical trial sites will then, upon an approval, flip to be able to deliver care clinically, and they will already have a good understanding of best practices and the translation of that into a real-world setting. Beyond that, you know, we're already doing some early thinking about what does the model look like right now within clinical trials, and what needs to be really standardized in terms of, you know, a number of preparation sessions or the timing of preparation sessions, to, you know, perhaps a more realistic version in a real world of, what are the required elements for safety for patients to prepare them adequately?
And there, of course, being the room with clinical decision-making, as is typical in medical practice, to determine how to best accomplish that. And so I... You know, I think as that evolves, then to your question about developing a playbook of best practices, you know, we'll see what our role is in terms of continuing to train therapists or train trainers of therapists, or other monitors within these settings, as well as what other support sites may need operationally to understand how to deliver the care.
That makes sense. And maybe we can wrap up here just on the recent financing or financing earlier this year, maybe less recent at this point, and then milestones as we look out over the next year.
Sure. Now, so in August, we were able to actually execute a PIPE that brought in $125 million upfront, with warrants exercisable at a 30% premium for another up to $160 million over the next three and a half years or so, which I think certainly sitting here now and looking back to August, we're extremely glad and very happy that we were able to pull that off. Not only was it the amount of money, which was clearly important and gives us runway into late 2025, including paying for complete execution of the Phase IIIs, but also the quality of the investor group that we brought in. It was really a very high-quality group of biotech healthcare investors, who we believe can be with us not only now, but for the longer term.
With that, as I said, we had cash of $248 million as of the end of September, and we have guided that that takes us into late 2025. We have the PTSD data coming in two parts: safety at the end of this year, the efficacy measure a little later. Summer of next year is key for the 005 primary top line. I would say those are the key events coming up over the next six-nine months.
Yeah. Well, that's a great overview. Really appreciate you both joining today.
Thanks very much, Gavin.
Thank you.