Good afternoon. Thanks, everyone, for joining us for the COMPASS Pathways Fireside chat here at the 6th Annual TD Cowen Neuropsychiatry Summit. With us from COMPASS, really big year for you guys, we have CEO Kabir Nath. We also have Chief Commercial Officer Lori Englebert and Chief Patient Officer Steve Levine. Thank you guys for joining us. I will be leading this conversation together with my associate and Vice President, Athena Chin. As I mentioned, game-changing 12 months for you guys for COMP360 and the company at large with the rolling NDA underway, recent executive order creating tailwinds for development. Guys, you recently reported phase III extension Part C data from Study COMP005, your single-dose phase III study.
I think high level at this point as we approach a potential launch, data suggests that additional doses, whether a second or third dose, provided incremental improvement with benefits sustained up to one year. We will just spend a few minutes on data before we launch into commercial. What is the data telling you about one retreatment, two retreatments, doses to remission, and how this will reflect in the real world?
Thanks, Ritu. I am actually going to pass that to Steve. I am just going to remind everyone that we will be making forward-looking statements, and you should refer to our risk factors. Steve, as a practicing psychiatrist, over to you, please.
Thanks, Kabir. Thanks, Ritu. First, just a reminder on the overall study design just to set the scene. As you mentioned, this is our COMP005 study, the phase III study comparing our 25-milligram COMP360 versus placebo in a treatment-resistant depression population. That is those with major depressive disorder who have been failed by at least two treatments in their current episode and represents a very severe and chronic population with an average duration of illness of at least three years in this current episode and multiple prior episodes. The overall design of the study included a primary endpoint at week six of change from baseline in MADRS. There was then a blinded portion, Part B, out to week 26 or six months, where participants could receive a single retreatment on a blinded basis.
Part C, which is the one you are asking about, and we have just reported top line on, which is open label, and this is an opportunity to receive a single 25-milligram dose, either those who have already been in the 25-milligram assignment or the placebo group. The key takeaways here is that this really reinforces the profile that has been emerging for COMP360. One thing we are really proud of, and it has been very reassuring to see across each of the points of data we have released, is how consistent they have been in each part of the study and also between COMP005 and our second study, COMP006.
Indeed, in this case, what we are seeing is for those who were already in the 25-milligram arm in Parts A and B, who may now be getting either a second or a third dose, we see a response to that treatment with similar rapidity and an increased depth of response that is quite durable. For those who previously had had placebo and now are getting their first dose of COMP360, it reinforces, again, that profile we are seeing of a very rapid response with very clinically meaningful and significant reduction in MADRS that is durable out to that 52-week time point, and certainly to the point we reported of six weeks post that dose administration.
Overall, what we are seeing is that with a generally safe and well-tolerated profile, there is essentially an immediate benefit for those who respond that is very durable, and with now one, two, or three treatments, durable out to 52 weeks.
Got it. Now let us jump straight into the commercial prep. You have reiterated that COMPASS expects to be launch-ready by the end of this year, with approval potentially in first half. How conservative, Kabir, is this first-half timeline, and what modules of the rolling NDA remain outstanding before the NDA is complete at this point?
Yeah. First half is realistic because there are a number of variables, and I will get to those. In terms of status, we are completely on track to complete the filing in Q4. I can confirm that. What is outstanding is the remainder of clinical data. Now we have all the data in-house that we require. But clearly, this is two large phase III studies, and we do need to integrate some of the data from that, specifically on the safety side. Really the work that is going on right now, we have a team working really hard to put together the final integrated summaries, particularly the integrated safety summary. But that is completely on track for completing the filing in Q4. In terms of the variables thereafter, there are limited precedents for an NDA. So there are a couple of questions.
First, will the agency still take 60 days to accept the filing? Then while the target for approval is between 30 and 60 days, they have made clear that is a target, not a commitment. Indeed, it may be that they issue a standard priority review PDUFA and then look to beat that. But again, there are so few precedents here that there is a lot of variability around that.
We have heard the division director call that 30 to 60 aspirational.
Clearly with a rolling submission and review, and, just to confirm.
Yeah.
there really is a rolling review. We are getting IRs, we are responding to IRs. It is clear that there is a high level of engagement. We can talk a little bit more
Sorry, Kabir, what are IRs?
Information requests.
Okay.
These are essentially queries from the FDA as to what we have submitted. What we have submitted is clearly under review, under active review. They are highly engaged. But to your point, Dr. Maurizio Fava has said that that is a target, not a commitment. Let me hand to Lori just to talk about the other key variable that goes into that first half window, which is rescheduling.
Yeah, thanks, Kabir. Hi, Ritu. As a Schedule I drug, we will need to be rescheduled once we have an FDA approval, because that means that there is medical use approved for the drug. The federal DEA typically has a statute of taking 90 days to reschedule a product. On average, they typically hit and they go to about 90 days. That is the expectation, is that they do that. However, the executive order back in April asked that the FDA and the controlled substance staff with the FDA work in closer tandem to try and pull those timelines in. How that looks and what that translates to in terms of timing is somewhat unknown.
What I can tell you is we're doing everything possible to help facilitate any potential to pull that forward, including already submitting our eight-factor analysis to the FDA so that they could start the review if they wanted to and hand off to the DEA in a timely fashion. Once federal reschedules, then the states need to reschedule, so that it can legally be prescribed and administered in a state. There are several states that will reschedule immediately upon federal DEA rescheduling. They're called trigger states.
Trigger states, yeah.
Yep. They just follow what federal DEA does. There are other states that require either legislation or regulatory pathways to adjust their statutes, and we have worked very hard over the past two years to pass legislation in these states t o make sure that that timeframe is within 30 days of rescheduling. Right now, if we were to get approval today and it were to be rescheduled, we have 93% of the population living in states that will reschedule within 30 days.
Just going back for a second, some of these information requests, have some of the information requests been on data that was part of the eight-factor analysis such that it suggested that it is already under active review?
We haven't disclosed that level of information around what the IRs are, Ritu, but what I can tell you is virtually everything that we put in, there is clearly an element of review. But again, to Lori's point, our ability to actually determine the speed at which CSS works, or indeed when they hand over to the DEA, we really don't have insight into that. Just to come back to your question the first half is a realistic window. There is clearly an extraordinarily unlikely scenario where we get approval and federal rescheduling by the end of this year, and that's why we have consistently said we would be launch-ready by the end of this year.
Again, the likelihood is this will fall somewhere in the first half. Again, as we get closer to completing the submission and dialogue with the agency, we may be in a position to tighten that range, but right now we're not.
Understood. Well, you know I have to ask, Kabir. I always do. Lori, the trigger states, do I understand this right? The trigger states will automatically convert to Schedule II or Schedule III within 30 days, or is it a shorter period of time?
It can be shorter. Some are immediate
Okay.
and they will do it the day that federal reschedules.
The day, yeah.
The majority of states, again, I think it's 44 or 45 states will reschedule within 30 days. So it could be day one after federal all the way to 30 days. So that's their commitment, is that they will do the rescheduling within 30 days.
For the five or six that are not trigger states, are any of them overlapping with how you guys have mapped major commercial geographies?
That's a great question. I first want to point out that just because they haven't rescheduled yet does not mean it won't be rescheduled with legislation by the time we get approval. There's still active lobbying. We're still actively working with those states to try and pass legislation prior to approval. So by the time we get to approval, they could already be rescheduled. It also doesn't mean that they won't reschedule, or they won't do it in a timely manner. It just means that they don't have anything on their books that forces them to do it within a timely manner. We will obviously have a very concerted effort at time of approval and rescheduling, working with these states to make sure they're all acting with as much urgency as possible.
Mm-hmm. Are any of them New York, Florida?
No.
California?
All your major, all your top 10. In fact, I think it might even be your almost top 30 states are, will-
Are trigger states?
Yeah.
Okay. The idea of being reclassified to Category II versus Category III, what is your expectation and what does II versus III mean for real world?
Our expectation, our base case is III, and I think if anything, the arguing would be that you could actually be down scheduled further. There is not that much practical difference between II and III, but Steve, maybe you want to comment on that specifically.
Yeah. Specifically, I'll stick to the provider perspective, which is probably the most significant facet of this, and that is in terms of the site preparedness, currently these sites are delivering SPRAVATO or ketamine, which is Schedule III, and so our expectation of Schedule III would be consistent with that. If it were Schedule II, the DEA rules around how the drug must be ordered, stored, handled, et cetera, are quite similar.
Practically, it would not make a very big difference for these sites.
What is the true real-world difference? Is it paperwork? Is it some sort of lockbox? Is it evidence of chain of custody or qualifications of who handles it? Anything?
Yeah. There would be more of a difference if this was a drug to be picked up at a retail pharmacy.
But given that it will be stored securely on-site, it really is just a matter of the difference of a piece of paper.
Understood. Okay. That is very helpful. Can you walk us through, Lori, I think this is a Lori question, state of commercial preparation and commercial site readiness. How ready are the existing interventional psych centers, particularly that 8,000 administering SPRAVATO? At a conference visit last week, I think there were some figures kicking around that really the majority of SPRAVATO doses or the majority of patients are in a much smaller number of centers, not just that 8,000. How do you tier these 8,000 centers, and how ready are they?
Yeah, that is right. I will start, and Steve can certainly chime in as well, based on some of the work he has been doing with the strategic collaborations. What you said is actually absolutely right. About 80% of volume is written in about 20% of sites. It is less than 2,000 sites that are writing a very large amount of volume of SPRAVATO. The remaining sites that are actually coming online and this phenomenon that we are seeing of interventional psychiatry centers growing at the pace that they are growing. Keep in mind, they are adding 500 sites a quarter, on average, over the past 18 months. That is a lot of sites coming online. Yes, SPRAVATO is a good drug, but they are coming online because they see what is coming, and that is these multi-hour treatments like COMP360 and psychedelics coming.
If you are capable and you are REMS certified to administer SPRAVATO, then you are attesting to you have the requirements that will be needed to administer these multi-hour treatments that are coming down the pipeline. This growth is happening, yes, because SPRAVATO is growing, but also because of what's coming down the pipeline for mental health. Yes, a large amount of volume of these sites that have a good understanding of how SPRAVATO is used. They have a good patient flow. Because remember, SPRAVATO is anywhere from 25 to 50 administrations in a year. So patients have to be within a certain radius of where they are able to receive SPRAVATO, and they have to be willing to come in very frequently.
When COMP360 gets to market, what you will see is that radius expands quite a bit. Again, some of these sites are already preparing for that. You ask about tiering. Yes, just like you would any traditional launch, you would tier the ones who are the most likely to prescribe out of the gate. All that means is that your sales reps or your field force is going to hit them at a much higher call frequency versus actually talking to them. We will have sales reps that cover all 8,000 and then some. We're even going to go beyond that and talk to referring physicians who are going to be referring patients or potentially could refer into these treatment centers patients that they may have sitting at their practice that are TRD patients that could easily be referred over.
Will that be the same?
Our sales.
Oh, sorry. Go ahead.
No. Please go ahead.
Will that be the same sales force that would detail the interventional sites? The folks or the program that will detail the referring physicians. Then how big is that pool of referring physicians that you intend to initially target?
We can make the pool whatever size we want to make the pool. We're adding, there's probably another 2,000, 2,500 physicians who have a very large pool and are in a close proximity to a site that would make sense to refer. So they have a very large pool of TRD patients that are TRD already.
These are psychiatrist referring physicians, right?
Not always.
Oh.
There's a very healthy PCP mix in there as well.
Because remember, a lot of PCPs are already treating patients-
Right.
with antidepressants and have likely already gone through at least two with the majority of their patients. There are some very high prescribing PCPs who are more mental health focused. That would make a lot of sense for us to make sure that they understand the profile of COMP360 and obviously treatment-resistant depression and the importance of getting those patients treated who actually are TRD.
What remains to be built out, Lori? Have you hired everybody or in what order are you hiring? In what sequence are you hiring before December 31st launch readiness?
Yeah, that's a great question. We have almost exclusively completed the headquarter build-out. We have grown tremendously from January to now, building out all functions that we'll be preparing for commercialization. What we are in the process of doing now, and where the primary focus is making offers contingent upon approval to the sales force. We've already done our territory mapping. We know where we need sales reps. The team is spending a lot of time making sure that we're getting good candidates. The demand has been mind-boggling on how much demand we're getting in terms of resumes coming in to be a sales rep at COMPASS.
We're in the process of starting to make offers contingent upon approval, so that once we do get approval, these offers become offers that they sign and get on board very quickly. That's not only for the sales force, but that's also very importantly important to note, which I'm sure you're going to get into with Steve on the CPT codes, is the reimbursement for the support and monitoring time at the sites. That is very, very important. We know that this was a stumbling block for SPRAVATO out of the gate. It is something, obviously, we learned. We do not want to make the same mistakes. We're also hiring a field reimbursement team that will be out in the field making sure that these sites are educated.
They are hand-holding them, making sure that they can get reimbursed for the time that they spend with-
That will be a separate. Whereas other drugs often have a patient hub for patient support, these would-
We will also have that.
Be site hubs. But you-
Yeah. We are going to do as white glove as possible, right? We are going to make any barrier to prescribing, we are trying to get in front of as much as possible. We will have a very robust patient support services offering for the patients. Especially in that time period where just like every other drug that launches, there may not be perfect formulary access out of the gate because that is how payers work. We will make sure that paying for the product is not prohibitive for the patient. Then, of course, we are going to make sure that sites can get reimbursed for the product.
Got it. What-
Just a reminder, Ritu, we have had MSLs in field now for nearly three years, and we have significantly expanded that group. From a disease state education and so on, and KOL engagement, we have an MSL team ahead of a lot of these other field-based resources.
That is a good point, Kabir. One thing that I think is very important and often missed is COMPASS definitely had the foresight of making sure that there was a field team out being able to do scientific exchange around psychedelics at large, but also around the trial design of the two phase III trials and then educating on COMP360 trial results.
Lori, one of the things that Athena and I took away from the recent FDA public hearing was that there are certainly constituents who believe that there should be not just a formal training program for clinicians and support staff for treatment and administration, but that there may be an inclination towards actual government licensing. Do you anticipate that site training, staff training will be more of a certification or something that will be more formal and potentially more rate limiting on the far side of approval?
I'll start that answer, and then I'm going to pass it off to Steve because he feels very strongly about this and has been enabling how we move forward, most likely as an entire class not just for COMP360 alone. We will be held to the REMS certifications that are required. Right now, based on early feedback from the FDA, we do not believe that there is going to be anything more than a licensed healthcare provider listed as the representative and the licensed prescriber on site. But Steve, do you want to talk about the things that we are also doing to help enable to ensure that that training is appropriate for these sites and those that will be administering the product?
Yeah. Thanks, Lori. First, we do recognize the responsibility that we have. It's a privilege and a responsibility to be first. And with that, we want to ensure that there are good patient and provider experiences in the early days of starting to market COMP360, as well as safe outcomes. And with that, we recognize that this is a treatment that most healthcare providers have not previously had experience delivering. Now, each member of a multidisciplinary team will be acting within their scope of practice, will be performing activities they perform every day. Psychiatrists know how to be psychiatrists. Medical assistants know how to assist medical stuff. But because we want to ensure that this staff is ready, then we just recently made an announcement that we are supporting through grants the development of training programs.
This will help people to know where they can go to receive training that will have them ready and prepared to deliver psychedelic treatments, not just COMP360. We are not limiting to those training organizations, so we simultaneously made materials available so that anyone who would like to design a training can do so and have guidance on the competencies that are important and the important principles that underlie monitoring and supporting patients having COMP360 and other psychedelics. With that, there will be very comprehensive training and education available to ensure a ready workforce, and this will be tied into our REMS, where the authorized representative will be attesting to the fact that everyone involved in treating a patient receiving COMP360 is appropriately trained.
Got it.
In the last few minutes, we do want to talk about reimbursement, given it is a key investor topic. As the first classic psychedelic to potentially enter the market, how should we think about the launch trajectory, especially if the new CPT codes and reimbursement pathways are still evolving at launch? Steve, do you want to-
Do you want me to start, Lori, and then I will hand to you on trajectory?
Perfect.
Yeah, Steve.
Yeah.
You start on CPT.
Great. First of all, even before I directly answer the question about CPT, I think it's important to say, and this ties back to some of the discussion earlier, that these sites, these interventional sites, are not a black box. They are the opposite of a black box. We know them intimately. We know them because, as Kabir said, we've had MSLs in the field for the past few years engaging with them. We know them because prior to my time at COMPASS between 2010 and 2020, I was building some of the earliest examples of them. I know many of these sites personally. Then there's our network of strategic collaborations where with some of them, including some of the largest networks of interventional psychiatry centers, we've been working with them closely over the past couple of years to understand any potential barriers to implementing COMP360 when approved.
With that, it gives us a lot of confidence that even if there may still be a few final unanswered questions about a finalized REMS or payer policies, things like that, we're very confident that there are no long lead time items. There are no major investments. There's no structural changes these sites need to make. They're ready. The physical infrastructure is there. The rooms are there. The means of monitoring these patients, along with patients simultaneously receiving other in-office multi-hour treatments, the staff that's involved as a team in monitoring and supporting these patients are there.
The segue to coding is, along with this, although it is not typical for a biotech or pharma company to be thinking about provider side economics, one of the key lessons learned from the SPRAVATO launch and the early difficulties there was that unless we at least understand the provider side economics and ensure that there is a framework in place, that will then be up to them, in order to properly code and to state their reimbursement. Unless we think about that ahead of time and ensure that framework is in place, that can lead to a delay in uptake. That is why we did the work a few years ago on securing the CPT III codes.
We do know that they will still be in their Category III form at the time of our launch, and they will need to be progressed to Category I and receive their final valuation. This is also why we will be supporting these sites with our field reimbursement specialists who will help them understand, what are the codes that are available for them to use and ensure that they are reporting things appropriately, so that way that progression happens and is not a barrier.
Do you have kind of a-
Yeah, I mean, on launch trajectory. Steve, you should. Go ahead. Go ahead, Athena.
Oh, just a question that came in, too. How long do you think it will take for those CPT III codes to convert to CPT I?
Based on demand. We're going to do everything we possibly can to push it forward, and also based on timing for the review. Our best estimate will be about 18 months. In the meantime, I think it's important to note that in the meantime, it does not mean they won't get reimbursed for the time. They will continue to use the same codes that SPRAVATO is using today, and they will get reimbursed at that rate. We just believe that the CPT, when they move to Category I, will be valued on an hour-by-hour basis in a favorable way.
Awesome. We are at time, so thank you guys so much for joining us today. Next up, we do have Rapport Therapeutics moderated by Joe Thome at 1:30 P.M. Thanks, all.
Thanks, Chin.
Thank you very much.