Good morning, everyone. I'm Sumant Kulkarni, a senior biotechnology analyst here at Canaccord Genuity, and welcome to the second day of our 46th annual Growth Conference. We're really pleased to have COMPASS Pathways here with us today. They are a pioneering company in the mental health therapeutic space, and it's a really interesting time for the field that they play in. As I said, they are pioneers. There is a product called COMP360, which is psilocybin. It's passed two phase III trials with positive results for treatment-resistant depression, which is a high unmet need indication. We're happy to have Steve Levine, who's the Chief Patient Officer, and Lori Englebert, the Chief Commercial Officer. They're the people in the hot seat right now, given where the product is at from a regulatory standpoint and from a potential commercialization standpoint as well.
In the audience, we have Stephen Schultz, who knows everything about the company as well. Thank you everyone for attending, and we'll keep this interactive. There will be a mic going around the room, so if you have any questions, please feel free to raise your hands, and we'll get a mic across to you. With that, I'll just ask you guys to set the stage a bit with a few opening remarks, and then we'll have an interactive session.
Thanks, Sumant. Good morning, everyone. First, just a disclosure, we may be making forward-looking statements during the presentation today, so please refer to our website and SEC filings for risk factors.
Nicely done.
Thank you.
Hi, everyone. Thanks, Sumant, for having us. I will just open up by saying, and echoing Sumant's comments, that this is a very exciting time for COMPASS and COMP360, as we are, as some may say, barreling towards a potential filing date, and potential approval. We had earnings last week, where we reiterated that we will complete our NDA filing in Q4 of this year. As a reminder, we have received, back in April, a national priority review voucher. We have also had agreement with the FDA that we would perform a rolling submission and review, and we also confirmed that the FDA is actively working through our early submissions. We have already started submitting modules, and the data is flowing into the FDA as we speak.
Whereas we will not have complete clarity on PDUFA dates and things like that, I can speak to you guys in generalities around what we expect in terms of launch, after the approval or after the filing is complete in Q4. The way that we are thinking about in terms of timelines, and Sumant, I will just go ahead and address that because I know it is a big question for everyone right now, is after the filing, the FDA may or may not take the typical, traditional 60-day acceptance period. That is an uncertainty with the priority review voucher, but we are hopeful that they can beat some of that timelines, given the fact that they are actively reviewing right now. Once that happens, they will likely give us a PDUFA date that is consistent with a priority review, given we have Breakthrough Therapy designation.
We are expecting a PDUFA date that seems a little bit outside of the one to two month review target that the FDA has set with the voucher, but that they will most likely try and attempt to beat that. Tiffany has stated publicly that the target is one to two months, but obviously that is a target. It is not a definite. There are examples out in the space. Foundayo with Lilly went for a 50-day approval. The FDA is actively working to try and beat the one to two month target they have stated. With that, we also have a Schedule I product that we are working with. We will need to go through DEA rescheduling after approval.
If everyone remembers, the executive order back in April stated that the DEA and FDA should work closer together to expedite that timeline of review for DEA rescheduling. That is also a bit uncertain in terms of timing. Traditionally, the DEA has 90 days to reschedule after an FDA approval, then the states will need to reschedule. Timelines from filing to approval feel very good for us to reconfirm that we expect a launch somewhere in the first half of 2027. As we get further along in our discussions with the FDA and closer to finalizing the filing, we hope to firm up some of those into a much tighter timeline. We are very excited. The market is excited. By market, I mean the physicians who will prescribe and the patients who will receive it.
We are having very active conversations with payers right now. We are looking forward to commercializing this, getting it to patients.
I think the room is excited. This is a nice turnout for an 8:00 A.M. fireside.
Yeah.
That is great. I think you answered all my questions there.
I can keep going if you like.
We value sufficiency.
The FDA, timeline-wise, we know this is just a one to two month target, right, quote, unquote. Given that and given DEA rescheduling is also strongly suggested by the executive order, there is nothing really that mandates that. How conservative do you think a 1H 2027 timeline is for a launch for you?
I think 1H 2027 feels very good for us. Again, obviously we are working to make sure that we can expedite this as much as possible. We have stated frequently that we would be launch-ready by the end of this year. There is a very important nuance to launch-ready versus launching, and that is if we were to receive an approval, given the uncertainty and the fluidity with our timelines, we would be ready. That is what our intent is. We continue to be launch-ready by the end of the year, but the likelihood is that given the uncertainties around the one to two month review period, if there is an acceptance period, how long the DEA will actually take to reschedule. That one half feels very good and solid for us.
Got it. I am going to stray a little bit off script here, but how is this product different from other products that you might have been involved in launching?
I have spent more than a decade and a half launching psychiatry products, and CNS products. This product brings a profile to the industry that is unlike anything that psychiatrists have ever seen. I will not speak for psychiatrists as I have one sitting right beside me, so I am going to pass this to him from a clinician standpoint. From a launch standpoint, being the first in a field that has historically had, let us call it baggage or stigma around it. What we are doing is really making sure that we have a strong effort to educate on the scientific rigor that we are applying in our clinical trials to make sure that this is a very safe product for patients.
What we are seeing in terms of results for patients is transformational, and we are doing it with one dose and then having durability that lasts out potentially more than six months for patients who are, on average, taking one to two, maybe even more antidepressants every day. This truly can be transformational for the industry, but also for patients. What we are doing a little bit differently is we are taking extraordinary care around the launch. This is an experience unlike many are used to, including the patients. There is SPRAVATO, who has been out in the field now for seven years, really setting the stage for these multi-hour treatments. Our experience will be different than SPRAVATO in terms of time, and patient and provider experience. But many similarities.
We are not coming in cold, but we are going to take extraordinary time, given we will potentially be the first to market in this pretty exciting space where we are truly going to make sure that sites do not have barriers to prescribe. Steve has been doing a lot of work with a lot of the high-prescribing SPRAVATO sites, as well as different care delivery networks to make sure that we understand what barriers may be when we launch. The approach is different in terms of launching, but the sentiment behind the care and time we were going to take with each site to make sure that these sites and the patients have good experiences is the real defining differentiating factor. But Steve, I do not know if you have anything to add.
Well, from a clinician's perspective, the profile is so fundamentally different. It is hard to even discuss within the same conversation. I am a psychiatrist by training. I know it is hard to tell because I do not wear a sweater vest, and I am not going to ask you about your mother. I also know what the MADRS is, unlike a lot of psychiatrists. This is really what brought me to COMPASS six years ago. The fact that what has been available for patients living with severe depression forever has been essentially different flavors of the same thing, which typically involves daily treatment and a calculus of risk-benefit that involves accepting daily side effects for modest benefit. That is something in treating thousands of patients with treatment-resistant depression I never felt proud of.
To now be in these late stages with two positive phase III trials and an application under active review for an emerging profile, which shows incredibly rapid onset of effect, where we are detecting a statistically significant and clinically meaningful difference in the MADRS as of the day following a first administration. Durability on a scale unlike anything we have ever even come close to in the past with one or two or perhaps three treatments having a durable effect out to at least six months with a safety profile that has been extremely reassuring with no unexpected adverse events. The vast majority of AEs being mild to moderate and transient and occurring on the day of administration. This makes it a very different set of considerations for clinicians and their patients of that risk-benefit decision, and really provides hope to millions of people who have been so underserved.
Yeah, this is unlike anything I have ever seen before.
Got it. Lori, to your point, you mentioned some of the baggage around this class of therapeutics, and life seems to be coming full circle now because these were sort of born in big pharma when they were synthesized. Now you are seeing Lilly in the process of buying AtaiBeckley. You saw AbbVie make this transaction with Private Gilgamesh Pharmaceuticals on brexpiprazole, and you saw Otsuka buy Transcend Therapeutics. As a pioneer in this space, what does that mean from your perspective, and what does that mean in terms of implications for when you commercialize COMP360?
Yeah, great question, Sumant. It can only mean great things, right? I mean, what is better as a validating factor in what you are doing than big pharma being interested? We see it as a tremendous step forward in starting to reduce some of the stigma around this and really, again, starting to validate the science. I don't think big pharma is going to make a bet on something that they don't believe the science behind. We feel very good about that. From a commercialization standpoint, we will have several years on market prior to big pharma coming. To be honest with you, unlike other situations where you have small pharma getting gobbled up by the behemoth that is big pharma that can throw 500 sales reps out. This is a very different situation because we know exactly who the treaters are, and it is very small.
In other antidepressants I've launched, you go out, you target 75,000- 100,000 physicians at time of launch. Here, we know exactly how many prescribers there are, and it's a fragment of that. We are looking at less than 10,000 are actually prescribing SPRAVATO. What that means is they have the infrastructure and the ability to continue to prescribe multi-hour treatments. This is a very concentrated prescriber group that is growing very rapidly, but it gives small pharma the ability to scale as the psychiatrists who are prescribing and the sites that are prepared to administer these multi-hour treatments can grow. It's less of a threat that you have multiple sales reps out calling on physicians as one would in a traditional antidepressant standpoint.
As you mentioned, this is a product that is extremely different from what people have been used to for something that's going to be out in the market. We do have a bit of a pricing benchmark with SPRAVATO, but you have a lot more durability than that product, far fewer visits to the clinic involved. How are you thinking about pricing bands and that kind of stuff?
The number one question I get. The way we are looking at things. Let me first set the stage. Given the fact that we have fairly recently, within the past three or four months, released additional data that we can start to really fully engage with payers so that they can understand the economic benefit and the value proposition of the profile of COMP360. Again, I've been in psychiatry for a very long time, and it is unlike anything I've felt from payer response. Now, let me caution, that does not translate into immediate access and great negotiations. But I have never seen payers more interested in understanding what this looks like. The number one response we are getting is, you see those results with one dose, maybe two? Their eyes are about to pop out. They cannot believe this.
We feel very good about where we stand with being able to really value the proposition, the economic value that this product can bring to the payer system, and that the payers will be receptive to it. In terms of pricing and where we're thinking about, obviously, we're still working through a lot of that right now, but given exactly what you just said in terms of the durability we're seeing, not to mention the immediate drops. This is a TRD patient population to which there is only one pharmacologic product out there approved right now, SPRAVATO. Payers really, truly value the fact that we proved efficacy in such a difficult-to-treat patient population. The chronicity of disease in the patients that we treated in our trial, unfortunately, it's not the patient's fault, it's that there are treatments that are not working for them.
They are causing a disproportionate impact to payers' economic system. They really are truly valuing the fact that we're seeing that drop immediately, 24 hours after dosing, and then able to provide that potential durability after just one or two additional doses.
Got it. Good. We have a question in the audience.
Can you sort of walk us through a typical patient experience in the clinic, and how does that differ to what a patient would see from what experience via SPRAVATO?
No one better to answer that than this guy here.
Hi. First of all, the key difference probably is just the length of observation time. With SPRAVATO, and per the requirements of the REMS, there are two hours of observation after the patient self-administers a nasal spray. This is with SPRAVATO. Typically, the dose of SPRAVATO is three devices. It will take a patient 20-30 minutes to administer all of those sprays. That needs to be directly witnessed. Then there is the observation period. Typically, the office is booking a room for three hours for that appointment. With COMP360, actually, we just published a paper which can give you some additional detail on this.
It is called Silence is Golden. It is a post hoc analysis of audio recordings from our phase II PTSD trial that we published last year, and we call it Silence is Golden because what you will see is that these administration day sessions are largely silent, almost 80% silent. Because what you would see if you were a fly on the wall is somebody lying down calmly, typically, wearing an eye shade, listening to music, and there is not talking, there is not engagement. You might hear a little bit of talking at the beginning of the session before they have taken the single oral capsule and seen the onset of the subjective effect. A little bit of talking at the end as they are coming back to the room and about to be discharged. In the middle, largely silent, and them lying down and listening to music.
Occasionally, somebody might have a bit of anxiety. It might otherwise be slightly challenging. That is when the team would, just as they are circulating amongst rooms, also attending to people receiving SPRAVATO or TMS, usually in the same clinics, would be available to support them. But there is no active therapy. There is really no active intervention during this time. It is a quiet period of observation.
What is the overall length of that visit?
About six hours.
Along those lines, given that this is a six-hour visit, and there could be huge implications for someone who is working in the workforce. When you do your commercial research, and this might sound like a bit of a tongue in cheek question, but it is not. What percentage of interventional psychiatric clinics are open from Thursday through Sunday?
I can start on that. I do not know that I can give you a percentage answer, but what I can say is, number one, Lori mentioned before that one of the things that is different about this launch versus other launches, the many that Lori has done over her career, is that we know exactly who is prescribing SPRAVATO today. Therefore, we know who to target. We do not only know who they are and where they are. We know them. We know them quite well for a number of reasons. One, we have got a medical science liaison team that has been out in the world for the past few years meeting with all of these sites. We have our network of strategic collaborations, which encompasses more than 1,000 of these sites delivering SPRAVATO today.
Those have been in effect for the past couple of years and involve deep information exchange back and forth to really understand all of the considerations for implementation of our product, if approved. It was also my entire world before COMPASS and running a company in this space for a decade prior to COMPASS. With that, we really have the opportunity to really understand the drivers of any of these decisions and how they're requiring patients, that patient journey, what the implications are for a length of treatment economically, treatment model design-wise, et cetera. One of the things we've heard from these sites that they're very excited about is they know the burden on their patients and their caregivers of SPRAVATO today.
As I mentioned, it's usually a three-hour appointment, but there are two of those per week in the first month, so eight in the first month, then it's weekly in the second month, and this is per label. Maintenance is either weekly or every other week, with the majority of patients continuing weekly. They need to be driven to and from these appointments as well. In total, that means that there are 25- 50 appointments per year, three hours, that patients need to be driven to. That is largely incompatible with working, and that's for the patient and for their caregiver. So highly burdensome, highly disruptive, probably one of the reasons why most of these clinics also have a lot of capacity. This is a burdensome treatment. They're also building capacity ahead of potential or anticipated approvals like COMP360.
What they anticipate for COMP360 is even though it's a somewhat longer observation time of six hours, the one or two treatments as opposed to the 25 mean that first they can recruit from a much wider radius, and they're already seeing this with some of their accelerated TMS treatments. It's something we're seeing with some of the state-level programs where it's primarily medical tourism. With very, very infrequent treatment, it makes it much easier for a patient and/or their caregiver to take one day off of work and dedicate that to a treatment. In fact, to make a nice day of it as opposed to having to accommodate scores of treatments over the course of a year and this being ongoing.
Clearly, this is going to be a really important product for patients. Now, from a financial modeling perspective, could you educate us on how a launch trajectory might look like once you have this product out in the market? Because it took SPRAVATO a long time to get to where it is today. Clearly, there are lots of learnings to be had from that, so you may not have a one-to-one experience relative to that. But again, this is a completely new type of product, so what should we expect?
Yeah. First, SPRAVATO, we obviously are taking a lot of the learnings from SPRAVATO and what they may or may not. It is just the benefit of going second. We have learned quite a bit and what they have done in this past seven years of really making sure, I say they, the infrastructure has built around SPRAVATO because it is really a product that does work for some patients, and they do recognize the need. These sites, this infrastructure is already established, and we are launching into 8,000+ sites that will already be able to adopt another multi-hour treatment fairly easily, whereas SPRAVATO launched into 0- 10 sites that were really prepared, and it had to grow from there. We already are coming in with the benefit of having this.
In terms of a launch trajectory, again, given we will potentially be the first out in the market, we are, and I mentioned earlier, we are going to take extraordinary care. We are going to make sure that there are no reasons not to prescribe. We are going to try and remove all barriers prior to launch, but a lot of that has to do with making sure that the sites can get reimbursed for the time that they are spending monitoring and observing the patient during, after administration, that the product can get reimbursed. These are things that if these go wrong, and they did go wrong for SPRAVATO for a very long time, prescribers will be disincentivized to prescribe because it is just hard. We are really going to try and make sure that we have a field reimbursement team working with the sites.
We are going to make sure that we are out educating. Again, we will be the first classic psychedelic to market. We need a lot of education, not only to those that are potentially prescribing, but the sites themselves to make sure that they are able to comply with REMS and that they are trained appropriately and really making sure that they are prepared for what the patient will go through. We are going to have extraordinary patient materials and patient support that we are going to provide the patient so that they are not disincentivized to take treatment. The ramp will be somewhat slow at first just because we are going to make sure that there is a very positive clinical experience for the site and for the patient.
I think the ramp will be somewhat slow coming out of the gate, but that once clinical experience starts kicking in, if we do our job really well, remove all the barriers, we make it very easy for the sites to prescribe, get reimbursed, and the patient experience is a positive one, that snowball effect will happen quite fast.
Yeah. If I can build on that just for a moment because it is a really important but somewhat subtle point. If we compare and contrast the initial slow ramp, the slow launch of SPRAVATO and some of the challenges they had with what we would anticipate, on the SPRAVATO side, there were real fundamental infrastructure barriers to their rapid adoption, right? The physical infrastructure, the clinic setting wasn't yet there, wasn't yet built. There wasn't a reimbursement framework in place. There really wasn't, up to that point, a marketed indicated product in treatment-resistant depression, et cetera. All of those things are different for us. We have no real rate limiting step or bottleneck to adoption on the part of the sites. But at the same time, as Lori said, we do want to launch with some care because ultimately this still is a first-in-class treatment. This is a psychedelic.
We want to really make sure that there are good early patient and provider experiences and good and safe outcomes at the start.
Good. We have a few seconds, so I'd be doing a disservice to your efforts if I didn't mention that you also have a program in PTSD. How excited are you about that? This is a bigger picture question which we can end with. The markets are large here, right? We appreciate that. We also appreciate that patients respond differently to different products. Given those variables, what do you think your key differentiator could be for COMP360 versus other psychedelic therapeutics that may also be approved and be on the market?
You want to start PTSD?
Sure.
Yeah. How excited are we about PTSD? Like jumping up and down excited.
Yes.
This is a huge unmet need. We talk about the 4 million patients living with TRD who are underserved. PTSD, there are 13 million adults in the U.S. with PTSD. They currently have two pharmaceutical options, but there hasn't been an approval in more than 25 years. Those are a couple of SSRIs, which are modestly effective at best. So this is a tremendously underserved population. And with the phase II study that we published last year, which was largely a feasibility and safety focus study, which on those fronts was extremely reassuring, we did also have an efficacy endpoint, the CAPS-5, which was a really exciting signal in terms of the response and remission rates that we saw. We are moving full steam ahead. We are screening patients.
This is a late-stage study, phase II-B/III, that is designed and is intended to be a single study for an approval. There are commercial synergies, high rates of comorbidities between those living with TRD and PTSD, so we couldn't be more excited about that.
Got it. On the differentiation of COMP360.
I will be quick because I know we're out of time. Just the key differentiation, we have the opportunity to potentially bring to market a product that can work in a very chronic TRD patient population who has otherwise not had efficacy on other products within one day. Then potentially provide that durability out to at least six months with just a couple additional doses over six months versus what's currently available on the market, which could be anywhere from 10- 15- 20 doses over six months.
Great. Thanks for that, and we're all out of time. So thank you for coming, and thanks for tuning into the webcast, and good luck on your efforts.
Thanks.