Good afternoon, everyone. I'm Sumant Kulkarni, Senior Biotechnology Analyst here at Canaccord Genuity, and it's my pleasure to have COMPASS Pathways here with us today. They're one of the leaders in this wave of the psychedelic renaissance we've seen. They are a mental health-focused company that has a product, COMP360, that just reported from top-line data on its first phase II trial for treatment-resistant depression. You guys are doing a lot of things to help patients in what is a huge unmet need indication. I'll turn it over to Steve. We have two Steves here: Steve Levine, who's the Chief Patient Officer, and Steve Schultz, who heads up IR. We also have Maura in the audience. She helps with all the IR stuff and outreach. Thanks for being here. I'll turn it over to you guys, and then we'll keep it interactive.
There will be a mic going around in case you have any questions. Please feel free to raise your hand.
Good. Sumant, thank you for having us. We appreciate that. Before we begin, I just want to make sure that you know that we'll be making forward-looking statements and that you should be referring to the risk factors of investing in COMPASS . As simple as that.
Cool. I like the abridged version there.
Yeah.
Steve, go ahead, please. Quick intro.
Yeah, just quickly introduce myself. As Sumant said, I'm Steve Levine, Chief Patient Officer. I've been with COMPASS Pathways for five years now. I'm a practicing psychiatrist. Prior to COMPASS, I came from the provider side of the world. My background really is in building new models of care delivery to deliver more novel treatments in psychiatry, starting in 2010. That was building the initial infrastructure to deliver ketamine for psychiatric indications, and then kind of blossomed into a national network of clinics delivering interventional psychiatry, which I then bring into COMPASS to start to think about implementation and scale should we have an approved product.
I'll start with some recent events, the political and regulatory landscape, which seems to be a significant tailwind for some of the approaches that you're using right now in the clinic. Do you see these political support endorsements as a tailwind or a headwind because they might raise expectations too much?
I can start with that. I mean, I think we would see them as neutral at worst. As many may be aware, these have certainly been prominent stories in the media. Several in administrative and government leadership have made statements supportive of the development of psychedelic treatments and recognizing that there are major unmet needs in mental health care broadly and specifically in indications like treatment-resistant depression and PTSD. This has cut across HHS leadership, FDA, VA, etc., in some cases making commitments to access for patients, whether it's community patients or veterans, within 12 months. That sounds like tailwinds. Naturally, those are high-level leadership making these statements. We still, on a daily basis, deal with the Psychiatry Division at FDA. Ultimately, these will be the decision makers.
Fortunately, the Psychiatry Division of FDA continues to be very engaged and responsive, as they've been for years with us now, having breakthrough therapy designation. We are having conversations, as you would imagine, both within government leadership as well as with FDA, trying to understand what is the synthesis of the support for psychedelics and some recognition that there is some urgency to meet these unmet needs with understanding what is the regulatory framework to potentially accelerate with our commitment to not lowering that bar. We firmly believe that rigorous science is important here, that the standards for the approvals of psychedelic treatments should not be lower than for any other treatment. There shouldn't be psychedelic exceptionalism.
With that, we also believe that we really are the only company developing psychedelic treatments at this point that, with the evidence we've generated to date, do meet the guidelines that FDA has put forward back from June of 2023 for what constitutes a sufficient evidence package for an approval.
You kind of answered my next question, but I'm going to ask it anyway. When FDA leadership says they would like to see a psychedelic therapeutic approved within the next 12 months, which product do you think is best positioned to be in that approved product and why?
Yeah, as you said, I maybe started answering that, but to give some more detail around it, we had a very large phase II-B study in treatment-resistant depression. This was 233 patients conducted in 22 sites in 10 countries. We saw a very robust primary endpoint achieved with a high degree of statistical significance. It was a three-week primary endpoint, but even at six weeks, which aligns with our phase III program, we continue to see a statistically significant separation of our 25 mg dose from the 1 mg active comparator.
With that as an active comparator study, combined with our recent announcement of the top line from what we call COMP005, our first phase III trial, which is our 25 mg dose versus an inert placebo, that together reflects that June 2023 guidance from the FDA calling for a complete package of both an active comparator study and a true placebo study.
I've gotten this question a fair amount from investors recently and over the time I've been covering this space, which is, do you think major biopharma companies will play directly in the psychedelic therapeutic space by acquiring assets? This question, the drumbeat's gotten only larger, like after or louder, I guess, after we saw some news articles on AbbVie potentially looking at Gilgamesh. What's your thought process on all that? Do you think an asset has to be a certain point in the clinic or beyond to de-risk it before major pharma dips in?
I'm going to start and fill in. Right, to your point, there were the recent articles that it's essentially rumor at this point, but nonetheless, of AbbVie's additional interest in Gilgamesh. Of course, they already have some investment in Gilgamesh, as well as other activity, Biotica and others. Certainly, there seems to be interest on the part of big pharma. We know that they are doing some work. We've had some conversations. We do see that as a validation of this area of science. We've also been consistent all along that we feel very confident that we are best positioned to commercialize COMP360, at least in the U.S. This is not your typical big pharma playbook of commercialization. This is not your 400- to 800- person salesforce detailing every primary care physician and psychiatrist in the country.
We have some unique skill set and experience in-house that we think really positions us well. Now, outside the U.S., there's the possibility we might look for a partner there. Bit early to have those conversations yet, but again, it's encouraging and I think validating of the space that big pharma is clearly doing more work and taking an interest.
Let's move now to some specific questions around COMP360, which is your synthetic psilocybin f or treatment-resistant depression. In your seat as Chief Patient Officer, what do you point to in the most recent phase III data set that you have as most exciting from a patient point of view?
I think it starts with the primary endpoint. There are many things we could highlight, but the mere fact that we demonstrated a clinically meaningful and highly statistically significant separation of our 25 mg dose from placebo at week six following a single administration is so highly differentiated from anything available to patients living with treatment-resistant depression today. The best comparator would be really the only product in the market that's currently being prescribed to patients with TRD, which is esketamine, SPRAVATO. In their trials, their primary endpoint was at week four after eight administrations. By week six, per their protocol, patients would have 10 administrations. Again, showing a comparable delta of our active dose from placebo at week six after a single administration, regardless of whatever durability that we expect to see with 26-week data, and we're pretty optimistic about that.
Even excluding that, the mere fact of seeing this effect at week six after a single administration as a clinician, as a practicing psychiatrist, and on the behalf of people living with treatment-resistant depression is a big, big deal.
Yeah, I would just add also that in that disclosure, the DSMB Safety Board issued a statement regarding the patients up to that point in both phase III trials, and that was a clean safety statement. That was very reassuring from a safety standpoint as well.
We've characterized your phase II data as really encouraging and potentially misunderstood by investors in our published work. Do you think, first of all, do you agree with that characterization? Secondly, what do you think was most misunderstood, if you do agree?
Yeah, I mean, I think it was at least initially misunderstood. I think there were a couple of points. Certainly, in conversations that we've had subsequently, we've been able to learn more about what perhaps was not fully appreciated initially. One of the things was with a 3.6 difference in COMP005 versus an inert placebo. With recent data from others where there was no placebo response, which we don't expect here because of differences in trial designs, but not knowing the absolute difference in each of the arms, it left open the possibility or at least people to assume that that might be the case. I think there was the interpretation that that might, in some way, add risk to the likelihood of success in our COMP006 trial, the second pivotal phase III, because that's versus an active comparator of a 1 mg dose.
Not understanding the difference in trial design, which was in COMP005, it was a measurement six weeks after a single administration. In the second study, COMP006, it's still a week six primary endpoint, but because there are two administrations three weeks apart, that six-week primary endpoint is only three weeks after a second administration. We think, if anything, COMP005 actually de-risks the likelihood of technical success in the second study. Another thing is, I don't think people understood how important that DSMB statement was that Steve referenced just before. The fact that that independent DSMB was reviewing not only the data from COMP005, the first trial, but also data from COMP006 concurrently. At that point, many patients were through part B or even part C of this study.
This is a big pool of patients at this point deep into the study with no new safety signals and no clinically meaningful imbalance between the arms. We think that to the extent there was any overhang of concern about safety, that this fully discharges that.
I would just add that I think there are also investors who may not have fully appreciated the comparability of the data that we produced with the SPRAVATO data. They are very comparable. We had been telling investors for months that our belief was that a 3-point- plus reduction in the MADRS would be clinically meaningful. That is really kind of the target that we were looking at. Of course, we exceeded that.
Right. Yeah, I think you'd characterize anything above three as a bonus, is what you'd said specifically.
That's right.
With that knowledge, what's been the reception to your data set from the neuropsychiatric community? Not necessarily the key opinion leaders or the experts, but rank and file kind of neuropsychiatrists.
We have a team of medical science liaisons that's out in the community speaking with healthcare providers every day. The feedback has been enthusiastic. I think that most psychiatrists are seeing this as an approvable drug at this point. They are too aware, very acutely aware of the unmet need and the limitations they have as far as available tools to meet that need at this point. I think they are optimistic about the approvability now of this product, and they're just excited to get their hands on it.
Have you had any engagement with the FDA specifically after you released the top-line data?
We've requested a meeting to discuss the data. We've announced now with our earnings call a couple of weeks ago that that meeting is scheduled for this quarter. With what we were discussing earlier about the regulatory tailwinds, the statements that are being made at various levels of leadership, certainly a topic for discussion at that meeting will be, despite the previous discussions of our base case, which is 26-week data from both of our phase III trials, what is the sufficient evidence package at this point? Considering our large phase II-B of 233 patients, are there scenarios where we could potentially accelerate a filing?
Right. You also applied for the Commissioner's National Priority Voucher process, right?
Yes, we have applied for the Commissioner's Priority Voucher, as of course, many likely have, given that it is a fairly easy application to complete. We look forward to hearing more detail about the selection process.
You said you have a meeting scheduled with the FDA for this quarter. That's a Type B meeting, right? You typically have 30 days after that to get meeting minutes. As a public company, what's your philosophy on disclosure? Would you disclose what happened at the meeting as soon as you get out of it, or will you wait until you have written meeting minutes in hand so you don't somehow mischaracterize what the FDA is trying to say?
Not necessarily either. This isn't our first Type B meeting with the FDA. We have breakthrough therapy designation that has afforded us robust and relatively frequent dialogue with the FDA over the past several years. Our policy to this point and likely going forward will be not to disclose every conversation that we have with the FDA. That would not be typical. That would probably not be welcome by the FDA. The most likely outcome of this meeting will not be a binary yes or no reaction from them. It will likely be some agreement to show them additional data at some point. Depending upon the nature of the output of that meeting, there may be material information to disclose. I think that the baseline expectation should be that in line with our previous practices, there may not be anything to disclose, even if it's a relatively positive outcome.
Given you've had so many interactions with the FDA, how has the composition of the team within the FDA changed, if at all?
They've been engaged throughout. They continue to, both within conversations as well as public statements, really seem to get the urgency of having approvals in the space and to be supportive of psychedelics as a class. Despite some of the news media suggesting that the FDA may be understaffed in some ways at this point or that they might be less responsive, we're not aware of significant changes within the division of psychiatry. They continue to be very engaged with our request for this Type B meeting. They responded quite quickly. We've been very pleased by their support and their engagement.
What about the specific people you've interacted with? Have those remained the same, or have there been substantial changes?
No, those remain the same.
OK. Now when we were getting into the top-line data for your first phase III trial, the part A of COMP005, you were crystal clear on what you should expect, which is placebo adjustment difference on the Mayer scale, P-value, confidence interval, and a high-level Data Safety Monitoring Board assessment. As you go into part B of that data set, what should investors expect specifically?
They're going to get a lot more information. With part A, we remained blinded. We still are blinded. All we received is what we communicated. We only had the points that you just mentioned. When we have 26-week data following part B, that will be a full data set. That will include all the time points up to that primary endpoint of week six and the endpoints that continue through week 26 with the data for the individual arms and all of the significant endpoints that will be analyzed in the two to three months it will probably take to analyze and clean that data.
Along with this, probably a more detailed safety table.
Right. We could expect to see like a placebo score from part A, all of those kinds of things?
Yes.
OK. This is a hypothetical, but I think a really interesting question. Retreatment-wise, what fraction of patients do you think might not need retreatment at all within the time frame that's contemplated for part B?
We may see some differences in COMP005 versus COMP006 because of the single administration initially in the first study and the two in the second study. Ultimately, we expect a number of patients to be retreated. As a reminder for those that aren't familiar with the study design, the trigger for that is MADRS driven. It would be those who have not yet remitted or who had but subsequently relapsed. At that point, they'll be offered the option of a single dose in part B. That would be in the same assignment that they had in part A because it remains blinded, or to start an antidepressant from a pre-specified list. We are going to get very interesting information from that.
It will help us to understand the effect of a second dose, the impact for those who perhaps were partial responders and who may now become full responders or remitters, and of course, longer-term durability of initial response or response after retreatment. This should be a very rich data set that will be very valuable for payers, for clinicians, for patients, of course.
Right. You mentioned durability. What's the sweet spot in durability? Is there any difference between what investors might see as a good durability versus patients versus payers?
In some ways, going back to what I was saying about the key takeaway for patients from COMP005 top line, we've already almost hit that sweet spot with a single administration, with the separation we saw to week six that is already highly differentiated. Now, if we look at the results from phase II-B, where those who were responders or remitters at the primary endpoint of week three, the majority of those sustained that out to week 12. From those at that point who enrolled in our long-term extension out to 52 weeks, many of them sustained that out to six months. We do expect to see durability well beyond that six-week time point. I would say that really anything beyond that is upside. It's gravy.
When you fast forward to a commercial time when this product is approved, do you still see annual pricing of SPRAVATO as a good benchmark for pricing of a product like this?
I think we're really going to need to see the full profile of the drug to answer that more clearly. We do anticipate much less frequent administration of COMP360 versus SPRAVATO, which is really significant in terms of the burden on patients and their caregivers who need to drive them to all of those treatments. We think there's potentially the opportunity to demonstrate value beyond that realized with the delivery of SPRAVATO. Again, we're going to need to see the data to really fully characterize the profile and make decisions and have conversations about pricing.
Got it. What do you think insurers might need to see to readily pay for a product like this?
We're encouraged by what exists today with payer policies related to SPRAVATO. In most cases, SPRAVATO has broad coverage, and in most cases, the policy language is pretty close to label. This is being approved for patients who meet that definition, the regulatory definition of treatment-resistant depression, which is third line. They've been failed by two treatments in their current episode. I think that that would be our goal. That's a reasonable expectation for us. I think if we continue to see the data that we've already demonstrated through phase II and already with phase III, that that would be realistic.
Let's take a situation here where you have product A, which is a non-psychedelic, and product B, which is a psychedelic. Let's say you have equal or equivalent efficacy. The durability is much better on the psychedelic. As a practicing psychiatrist, what would you prescribe and why?
As a psychiatrist, what's always going to guide those decisions is a conversation with a patient and individual patient characteristics, their clinical picture, their preference. There may be some patients who may be more accepting of a psychedelic treatment versus others. There are certainly many patients who value not having to take daily oral treatments and have that burden of side effects. Ultimately, this is a lot of patients we're talking about. Specifically with treatment-resistant depression, there are 3 million U.S. adults living with TRD right now. Last year, only about 50,000- 60,000 of them got SPRAVATO. Many of them are receiving daily oral antidepressants, even though they have not necessarily shown efficacy in that population. They may just be languishing on those. The consideration of a non-psychedelic at this point has to be theoretical because there isn't one that exists that has shown efficacy in that population.
Again, in that theoretical scenario, it will come down to patient characteristics and preference.
It's a bit of a cynical question, but is there anything like how much money can be made by portions of the supply chain that apply to this product, given that you might have a really durable effect? People may not be going in as often. Anything like that we should consider from an investor cynicism standpoint, I guess?
Not necessarily. Right? Yes, the frequency that's required with SPRAVATO means X number of sales per year and X number of visits for a provider, although that also places burden on patients and caregivers. It is challenging for the capacity of these centers, given the frequency of treatments. With our product, yes, less frequent treatment. We think that the value will lie in the efficacy outcomes, the patient experience, and the fact that there, as I said before, are too many patients with treatment-resistant depression. Even if the same patient isn't treated frequently, there are many others who are waiting for care.
Do you think to achieve real commercial scale, given the size of this market, you would need a setting where three or four patients are treated at the same time in the same room? Or would you be able to achieve scale at one patient per, I guess, treatment?
The latter. If you look at SPRAVATO delivery today, it typically is in private rooms, one patient per room. The interventional psychiatry infrastructure has scaled dramatically in the past six years since the launch of SPRAVATO, where in 2019, there was very, very little interventional psychiatry infrastructure. There are now 6,000+ sites delivering SPRAVATO. About 80% of those prescriptions are concentrated in a small number of those centers, about 1,000. Most of them operate multiple rooms simultaneously. They typically have a team-based approach to delivering care, where there's one prescriber on site that might be a psychiatrist or a nurse practitioner, and then nurses, techs, et cetera, who are helping to manage multiple patients.
Almost out of time, but I don't want to ignore the program that you have for post-traumatic stress disorder, PTSD. On that, you had some promising data. Could you talk about your next steps and whether it would be a phase II or a phase III trial that you expect to run? Would you open that up to all types of PTSD, including complex PTSD patients?
We are really motivated to move forward as quickly as possible in PTSD following the negative Lykos decision, the CRL last summer, and then a negative AdCom recently for bexpripazole. The unmet need remains. There's 13 million U.S. adults living with PTSD. There hasn't been an approval in that indication for a couple of decades now, another area of high unmet need. We are currently finalizing the design, and we will, forthcoming, be releasing more detail about which populations we'll be enrolling. We have said it will be a late-stage trial, but more information to come.
I'll squeeze one last one in. Investor question for you. What are the specific data sets that you expect to see within your current cash runway, and could you remind us exactly what that cash runway is?
Yeah, so the catalysts that we have coming up are for the phase III trial, for the COMP006 three-arm trial. We expect the 26-week data in the second half of next year, 2026. We will also have 26-week data from the COMP005 placebo trial. That is dependent upon completing part A, the nine weeks of the COMP006 trial. That will come ahead of that. We will have more information on PTSD. We've got a regulatory landscape that's interesting and dynamic. There's a lot going on in the company. It's an exciting time for us.
I'll lay it out. I had to kick myself. I didn't ask you this question. I'm going to ask it. How do you view COMP360 with its six- to eight-hour time in the clinic as a competitor relative to shorter-acting psychedelics, like the atai- Beckley program, like the GHRS program with 5-MeO-DMT?
Yeah, we don't necessarily see them as competitors, even if it's the same indication. Given the size of the unmet need, I think this is not a winner-takes-all environment. We need more tools. There will be various patient characteristics and other decision points that might point a clinician or a patient towards one treatment or another. We do think we have a head start. We will likely be on the market well ahead of some of these other options. Ultimately, positive data for those programs, I think, is good for the field. It's good for the sector. It's good for patients. We welcome more approvals in this space.
Thanks for that and all the work you're doing on behalf of patients. Thanks again for coming, and thank you for tuning into the webcast.
Thank you.
Thanks so much.