Your seats. I am Josh Schimmer from the Cantor Biotech Equity Research team, and very pleased to introduce the wonderful COMPASS management team. Couldn't really ask for a better-equipped trio to be leading this next phase of psychedelics as we transition to the commercial outlook for them. From COMPASS, we have Kabir Nath, Chief Executive Officer, Lori Englebert, Chief Commercial Officer. Sorry, Kabir, I said Chief Executive Officer.
Yeah, you did.
It has been a long day, so words are starting to jumble around in my head.
Us too.
Even without any soul-sucking.
Trust you.
And of course, Steve Levine, Chief Patient Officer. Welcome. Thanks for joining. I figured we'd spend our time maybe addressing some of the investor topics and debates that come up as we talk about COMP360. Maybe before we get into the Q&A, though, Kabir, just set us up with where COMPASS Pathways is today and what we should be looking for over the next year or two.
Thanks very much, Josh, and it's great to be here. Just a reminder, we will be making some forward-looking statements right now. COMPASS Pathways is the leading company in psychedelics. We have started a rolling submission for COMP360 for treatment-resistant depression, and these are patients with chronic, recurring refractory depression. That will be important to bear in mind as we go on to talk about the opportunity here. The rolling submission is underway. The FDA has commenced its review. We will complete that submission in Q4 of this year. We were awarded an executive order, through the executive order, post that executive order, a National Priority Voucher for an accelerated review.
With that, with a filing due to complete in Q4 of this year, with the potential for an accelerated review, we are expecting to launch in the first half of 2027. COMP360 in TRD, there is only one drug approved today, SPRAVATO, esketamine from J & J. COMP360 is clearly highly differentiated from that in terms of rapidity of onset, durability, and the just very limited number of doses needed to sustain that effect. We are extremely excited about the year ahead of us, about being potentially the first psychedelic to come to market. We have also just started, and it is now underway, a late-stage, potentially registrational study in PTSD, where we also see a very, very significant opportunity, and again, just like TRD, a very underserved market.
What is left to be done to finalize the NDA submission for COMP360?
We now have all the data required for it in hand. Today, we put out the 52-week data from the first study and that safety database, and that was consistent with everything we have seen. That safety data will go into the filing. Right now, we are actually finalizing the integration of the two studies, the ISS. The team is working very hard on that, and that will be the last piece of the clinical module to go in. Pre-clinical, CMC, others are already in, already under review. We are already getting information requests on those.
Any other highlights from today's press release to flag here?
I'll hand to Lori to talk about what it really means for the commercial profile and how it really, again, strengthens what we're already seeing for COMP360.
Yeah, we're really excited about the data that came out today for our open label portion of Part C for COMP005. That data really does help in three ways as we prepare specifically for the commercial launch. First and foremost is that it helps us start to understand what the average number of doses will be on an annualized basis. This becomes important because this is how we will likely price the product on a per dose basis on an annualized price. This really does help us construct the profile that we will put in front of payers as we start initiating our negotiations with payers. The other piece that's important to this is that it really does help us guide physicians in terms of what to expect for redosing.
That becomes important because open label data is extremely important for physicians because physicians like to take a look at what happens in open label data from clinical trials to have an analog as to what will happen in the real world. Of course, they understand, and they look at the double-blind piece when they're trying to understand the rigor that was applied and the scientific integrity that went into the clinical trials. But the open label portion of data really is more indicative of what real-world looks like. So we're pretty excited about the data that came out today.
Can you elaborate on that, Lori? Because I think you've guided to maybe three to four treatments per year for patients. As we think about what is that real-world experience that they're going through that might have them coming back at this particular frequency?
Yeah, I'll certainly start, but then I think it would be important to hear from the clinician up here. So what we're seeing from the data and what we expect is there will be an average of about two to four, which is about three on an average basis. But it will obviously have some variation based on patients. It's important to note that in our clinical trials, we have only ever studied four doses in one year. So we're not seeing a need based on the data immediately from the clinical trials for anything more than four. So that's why we're estimating somewhere in that two to four range. But in terms of when a patient may need to be redosed, the dosing portion of the label will say two initial doses, minimum of three weeks apart, which is analogous to our COMP006 clinical trial.
But then it will have upon physician discretion afterwards, and then I'll turn over to the clinician of how physicians and patients may discuss that.
Yeah. Steve, maybe as you address this question, you can also give us a sense as the trigger for requiring another dose, is it a dramatic kind of precipitous relapse, or is it kind of an ebbing of, or a slow recurrence of symptoms that might trigger a repeated administration?
Yeah. As Lori went through our expectations for what the dosage and administration section will say in our label as two initial treatments and then ongoing treatment or additional treatments as clinically indicated, it allows for some latitude on the part of clinicians in discussion with their patients to make the determination of the appropriate time to re-treat. That's important here because this is a heterogeneous population, and there will be different trajectories of initial and ongoing response. It's one of the reasons why in previously reported data, in our Part B data for both COMP005 and COMP006, we broke out cohorts based upon their initial level of response. Those who were non-responders, those who had at least a clinically meaningful benefit, as well as full response, and then remitters.
It may be that somebody who, 24 hours after a first dose, goes into remission, may not want or need a second treatment for some time. Where somebody else who may have had some initial benefit, let's say a 25% reduction, it may make sense for them to have that second treatment at least three weeks after the first or at some point more distant. Then in consultation with their physician to determine what is the right time to think about a next dose. Is it if symptoms are recurring at all? Is it if they're having a more severe depression? Or would they want to perhaps have a treatment at some more distant point, even if they're feeling relatively well, to help prevent that relapse? There will be that flexibility.
When patients do relapse, is it kind of a precipitous new onset of symptomatology, or is it kind of gradual crescendo of more depressive symptoms?
Again, a heterogeneous population, the likelihood is it is some mix of those. We do not have enough of the patient-level data yet to necessarily characterize in that granularity, the course of the timing of relapse.
Okay. One of the key investor debates and discussions around the dataset is with a three to four point MADRS placebo or one milligram controlled benefit, that is a small increment relative to the baseline MADRS score, which could be in the 30s. So it is potentially only a 10%-type improvement. Yet you kind of juxtapose that with the enthusiasm for this product and profile. I think investors also maybe get very caught up in competitive datasets that show really dramatic drops in MADRS score, and kind of wonder, well, why is there such, again, enthusiasm for this three-point benefit? So maybe you can provide a little bit of context to bring that signal to life in ways that the headline data may not imply.
I will start, and then I am sure both Steve and Lori will want to weigh in. I think it is really, really important to understand the patient population. We treated, in our phase III trials, a population of patients with true treatment-resistant depression, whose average duration of current episode was three to four years. We were extremely rigorous around ensuring that they had been failed by at least two antidepressants at adequate levels, at adequate duration, and that those failures were documented. That is the strictest definition you can have of treatment-resistant depression. This was really at the extreme end of chronicity. There is very robust data published that says actually length of current duration is the factor most important in driving lack of response to traditional antidepressants.
This is a population that really has very, very few other options, and that stands in stark contrast to a typical MDD trial, where typically it is either first episode or it is a short duration. In fact, there are other studies, and one of the more recent, highly publicized ones was nine months. That is as far away from TRD as you can get. It is really important to contextualize that. Let me hand first to Steve to talk, as somebody who has treated many of those patients, why that MADRS difference is incredibly meaningful for that group.
A few things there. First, naturally, when you are talking about a delta between three or four relative to our comparator, that is an average of those who have responded and those who have not responded. Back to Kabir's point about this population in TRD, naturally, there are many non-responders in our study, unfortunately. For those who do benefit, likely they have had a much more significant drop in their MADRS relative to those who are non-responders. Add on top of that we are seeing statistical separation as of the first measured time point, just 24 hours after that first administration, and then a durability on the scale we have never, ever seen before with one, two, sometimes a third treatment, having durability out to a year. That gets us very excited. Then add on top of that, this is a very difficult population to show efficacy in.
There is only one other approved pharmacologic product in TRD, that is SPRAVATO. They had a very comparable MADRS difference in their trials for approval. But for them, it was a week four endpoint, and it took them eight treatments to get to that week four endpoint, as opposed to our one or two treatments with a week six endpoint. It cannot be overstated how important that is for patients and their caregivers, given how burdensome that can be to have to be maintained on such a frequently administered treatment. SPRAVATO ultimately being administered 25- 50 times per year. That is 25- 50 days off from work for a patient and their caregiver. The last thing I will add is that in this really difficult and chronic-to-treat population, any change in MADRS potentially can translate into a significant impact on quality of life and potentially be life-saving.
I guess one of the key challenges as we try to compare data sets across psychedelics is, outside of SPRAVATO, there's no real apples-to-apples trial design comparison to even be made because we see some in an MDD setting that's very different than TRD, and based on protocols, probably very hard to even come up with a cross-trial comparison. All right. So another key investor debate is the delivery of COMP360 is very involved. It's a multi-hour experience for the patient and for the center, and how are centers really going to be able to incorporate such a cumbersome protocol into their day-to-day practice, especially as much faster, shorter treatment options may emerge from the psychedelic space? Maybe you can address that and talk to the burden of an interventional psych practice to administer psilocybin.
What's involved, and why they might not necessarily just go for the shortest experience possible.
There's a number of ways to answer that. I'll start with a couple of them. Lori will have things to contribute, I'm sure. First, you know I do impressions? I'm going to do an impression of somebody having a COMP360 session. Ready?
Let's see it. That looks good.
Yeah. That's what happens. That's not that complex, right? It is really somebody sitting there silently, having a quiet, pleasant experience for those six hours. They're wearing an eye shade. They're listening to music. It's actually a really easy day for the sites, contrasted with SPRAVATO, perhaps, which is a shorter observation period, but that really adds operational complexity. To have to keep turning that room over in order to have your room adequately paid for, you have to keep it full, which is not easy, especially when you're trying to convince someone to come in twice a week initially for the first month, and then frequently thereafter. We believe this will actually, in many ways, be an easier treatment for sites to deliver. One that is very predictable, and one where we provide them a lot of support to make this as easy as possible.
Maybe that's a good transition point to segue to Lori.
Yeah. I'll add on to that, but one thing I also want to just mention is you're taking a day for a patient, two, three, four times on an annualized basis, versus two to three hour appointments 25- 50 times a year. Whereas the sites may be churning these patients, when a patient is offered one of only potentially two TRD products that are available, and the physician says, would you like to come in 50 times a year? That means taking 50 days off of work.
Oh, by the way, you have to have someone drive you home every single time. Or, would you like to try something that you could potentially know within 24 hours if it works, and if it does work, you may only need to take it one or two additional times the rest of the year? The choice becomes quite obvious to patients as to what they prefer. On top of an easy day for the site, and oh, by the way, these sites are already prepared for COMP360. There is capacity in these sites. They don't need to build out anything additional beyond what they already have for SPRAVATO. They already have the staff available to help these patients during the administration, so there's no incremental burden for the sites already. This becomes a very easy patient choice.
How do we try to capture the caregiver requirements as we move from the clinical trial setting, where it's mandated to have direct observation of patients, now to a real-world practice where maybe they don't need to be in the same room, maybe you can put a patient on a video monitor screen. Help understand the resources real world that may be required on a per-patient or group of patient basis.
Yeah. First, we don't expect anything in our label or REMS to require anything from a staffing perspective that's different than SPRAVATO. In that way, these sites have already figured out how to do this, and they leverage a team. That team is usually comprised of a single prescriber on-site, and that could be a psychiatrist, nurse practitioner, physician assistant. Then it's a multidisciplinary team made up of nurses, medical assistants, technicians, et cetera. They, as a team, circulate amongst multiple rooms looking after these patients. They use CCTV cameras in the rooms, which is a very cheap and easy-to-install technology at this point. What becomes most important is that the patients in these rooms know that the team is present and able to support them if necessary.
There are many ways to create that sense of presence for them and to help them be assured that the staff is ready to support them if needed, which is almost never needed, without actually having to have somebody hovering over you in the room the entire time.
Does there need to be constant eyeballs on the patient, whether it's in person or on video? Or can you just put a patient in a room, shut the door, and if they come out, deal with that, otherwise, just wait till the end of their experience unmonitored?
I think at minimum, they will have CCTV cameras in the rooms, and the monitor is in a central place, and the team has access to always being able to see what's happening on the monitor.
Are there kind of outlier experiences with psilocybin that a center might need to worry about, just given the data that you've generated from clinical trials? What practically goes wrong, if anything?
Nothing necessarily specific to psilocybin. These are people living with treatment-resistant depression. This is a very difficult illness. They often have complex lives. It's an emotional time. And so like anyone going through a difficult time, you could be emotional at some point. You could feel anxious. You could have the range of human emotions. And that's the reason why it's nice to have a team of nice people being nice to you in the center as you're going through a treatment. But beyond what would be expected that could come up in that situation, there's nothing necessarily specific about psilocybin that these sites need to be prepared for.
Fortunately, of all places to be in, they're in the care of a psychiatrist who I'm guessing is fairly well-experienced in managing such-
This is what they do.
emotions.
Yes.
This is what they do. I also just want to add to Steve's impression, which was spot on, around what the patient actually is doing during the administration time. We actually have published data based on results from prior clinical trials called Silence Is Golden. These patients are typically, for 80% of the time, not speaking. They are actually sitting there, laying there. It's an inward. Psilocybin is a very inward experience. Any talking that takes place is typically after they take the product and during the onset, then at the very tail end.
Okay. Reimbursement comes up fairly often in discussions around COMP360, and we had such a fascinating discussion last night over dinner.
I don't know that everyone would agree with you on that.
I'm pretty sure everyone was riveted by our discussion of G-codes.
Yeah.
Because it doesn't get any more fascinating and exciting than that. Maybe help us understand the evolution of SPRAVATO reimbursement and what G-codes are and why it matters, and how you think it'll evolve with COMP360.
Yeah, just starting it from a high level. We are taking a very different approach to both the coding and reimbursement of our drug product, as well as thinking about the provider side economics and how they'll be reimbursed than J&J did in anticipation of the SPRAVATO approval and launch. It hadn't been the case in psychiatry prior to SPRAVATO that big pharma had needed to think about provider side economics, so they didn't do much work there. Partly because of that, what happened was they were issued codes which were not optimal, that in many cases bundled together the drug with the observation period that's required, and it's led to suboptimal reimbursement. Taking notes from that, we did early work to apply for new codes, which are specific to the administration of psychedelic treatments.
Because they are specific, they really are intended to and will capture all of the value being delivered during that visit as far as all of the work being done and all of the practice expenses. We have high confidence that because of that, on an hour-by-hour basis, providers should be adequately compensated for their time, and most likely at a level above what they're getting for SPRAVATO today. Additionally, we're keeping the CPT observation coding separate from the drug so that providers also have the opportunity, if they choose to buy and bill, to get additional revenue of the ASP + 6%.
Okay. Lori, you've talked about needing a few quarters for things to really start to inflect in terms of adoption. What are those things that you need to really have in place post-approval before you feel like the field is really primed to adopt COMP360?
Yeah. Most importantly, we will need the DEA to reschedule the product. The DEA, given that it is a Schedule I product currently, the DEA will reschedule after an FDA approval. Statutorily, they have about 90 days to do that. However, the executive order in April really encouraged the control substance staff at the FDA and the DEA to work in a much faster fashion to reschedule the product faster. Somewhere in between that 90 days, we expect federal to reschedule. We also then need the states to reschedule. For a physician to prescribe the product in the state that they reside, the state has to also reschedule it. We've done a lot of work over the past three years to make sure that the states are acting in a very fast fashion after federal.
Right now, about 92% of patients live in a state that will actually reschedule within 30 days of federal. We do expect that timeline to be somewhat truncated based on all the work that we have done, as well as hopefully some expedited DEA rescheduling. Concurrent to all of that, while all of that is ongoing, we will do things like bring the sales force on board, make sure that they are highly trained. We will make sure that the sites are getting REMS certified, which is a relatively minimal checklist, but we will have a team out ensuring that sites understand what is required from REMS and get certified for REMS so that once the states do reschedule, all of this can start taking place in terms of patients getting dosed.
In terms of timing for all of this, and Steve mentioned this earlier, we take very seriously that one of the biggest barriers to adoption of a product will be that sites don't get reimbursed for the time that they spend to administer the product and monitor the patient, or that the patient cannot get the product reimbursed themselves, the pure product. We are putting in place a lot of effort to make sure that sites are able to get reimbursed and that we are providing support for these sites so that they have ways to make sure that they are coding correctly and getting reimbursed so that not being able to get reimbursed is not a barrier to their prescribing. We will do that by the form of having a field reimbursement team out, working with these sites.
In terms of the drug getting reimbursed, we will have patient support services that we will make sure that the product is not also prohibitive financially for the patients to be prescribed. This is important because a lot of this is going to take time. We're going to make sure that the sites are well-trained. A site experience, a patient experience, these are all very important when you're coming out of the gate with something as novel and as innovative as COMP360 will be to the psychiatry space. We do expect that the launch timeline in terms of revenue, that ramp will be a little bit slow in the beginning just because we are taking good care to make sure that everyone is having a good experience.
But we do expect the adoption to go quickly once we prove to the sites that you can get reimbursed, that you're not going to have problems getting the product reimbursed as well. And patients have a good experience.
Given the time that you described, do you expect to have a permanent J-code when you launch?
You can launch regardless of if you have a permanent J-code. We'll have a permanent J-code, typically takes about six months.
But part of that will be consumed by the DEA or et cetera.
Sure. In terms of what we're thinking about, we're really going to be looking at new prescriptions. Given our infrequency of dosing, TRX is not going to be a real meaningful analog because, especially during that first year, it's going to be who gets dosed for that first time. TRXs will be once we start seeing redosing, which could be quite a long period of time in between the new doses. We will make sure we communicate very clearly what our KPIs are at launch and what we will qualify as success.
Once there is a permanent J-code, does that address any questions around drug reimbursement for centers? Is there still work to be done subsequent so that centers can confidently write and expect to be reimbursed for the product?
It does help with reimbursement. However, given the fact we will have patient support programs through the form of co-pay assistance for these patients, especially in that early time period where there is a temporary J-code, but also we're negotiating with payers for formulary access, we will make sure that patients can get the product. It should not impact the script uptake, but it certainly will start impacting revenue uptake once we get this.
Can't finish a discussion without at least touching upon PTSD. You've generated some open label data and are embarking on a phase III program. What gives you confidence in interpreting that open label data to portend a positive placebo-controlled outcome?
Yeah. First, the open label study first was a safety study, so that was the most important thing. We are confident based on that and everything else we've seen through the COMP360 program, that safety in PTSD is not going to be an issue. The efficacy signal was extremely strong, recognizing an open label population. We also had the opportunity to talk to each of the participants there and really understand the nature of the experience. To be clear, the support that was provided for PTSD was exactly the same as TRD. Based on that, based on those insights from the patient, based on a number of other concurrent studies that are running at academic centers and IITs around PTSD with psilocybin, we actually have a lot of confidence that we will see that signal.
Obviously, it won't be the same as that small open label study, but that we will still see a significant signal. We are also doing this as a two fixed dose study because again, one of the reasons that we waited to start it was until we'd seen COMP006 data. It is going to be a two fixed dose study, which again, we believe maximizes the likelihood of efficacy. Maybe in our last few seconds, Lori can comment on why PTSD is so important.
One, there is high synergies with the current commercial infrastructure. PTSD patients are treated at these sites of care that TRD will already be being utilized at. Most importantly, there are 13 million patients with PTSD, and only two approved products that were approved 25 years ago. There has been a complete dearth of innovation in this space, so new products coming to this patient population is very important.
We are just scratching the surface, but fortunately, we get more time at 4:30 P.M. as part of the psych panel. Steve will be-
Be there.
joining with a couple of other company representatives to talk a little bit more about access. Plus, we had a wonderful dinner last night that we will be summarizing in our note when it does come out, so stay tuned for that. Thank you to the COMPASS team. Thanks everyone for joining.
Thank you, Josh.
Thanks so much, Josh.