Ladies and gentlemen, thank you for standing by. And welcome to the COMPASS Pathways First Quarter 2025 Earnings Call. Please note that this call is being recorded. After the speakers' prepared remarks, there will be a question-and-answer session [Operator Instructions]. I'd now like to hand the call over to Steve Schultz, Senior Vice President of Investor Relations. You may now begin, sir.

Welcome all of you. And thank you for joining us today for our first quarter 2025 results conference call. Again, my name is Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways. Today, I'm joined by Kabir Nath, our Chief Executive Officer; and Teri Loxam, our Chief Financial Officer, who will have prepared remarks. In addition, Dr. Guy Goodwin, our Chief Medical Officer; and Dr. Steve Levin, our Chief Patient Officer, will be available for the Q&A. The call is being recorded and will be available on the COMPASS Pathways' Investor Relations Web site shortly after the conclusion of the call and will be available for a period of 30 days. Before we begin, let me remind everyone that during the call today, the team will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as amended. You should not place undue reliance on these forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and and other factors, including those risks and uncertainties described under the heading Risk Factors in our most recent quarterly report on Form 10-Q filed with the US Securities and Exchange Commission and in subsequent filings made by COMPASS with the SEC. Additionally, these forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements, even if our estimates or assumptions change. I will now hand the call over to Kabir Nath.

Thank you, Steve. Good day, everyone. And thank you for joining us. Recently, we announced the completion of dosing of all participants in Part A of our 005 trial, the first of two pivotal Phase III trials, which marks an important milestone in our mission to address the pressing unmet need in treatment resistant depression or TRD. We look forward to sharing the six week top line results in late June. As we've guided before, these results will include three key efficacy measures for the six week primary endpoint. The difference between the treatment arm and the placebo arm in change from baseline on MADRS, the associated p-value and confidence interval. A positive treatment effect of six weeks based on a single dose of COMP360 would represent a meaningful improvement in durability compared with the very limited options available to TRD patients today. From a safety standpoint, the independent DSMB reviews unblinded safety data on a regular basis and has been doing so since the trial started. Since the trial remains blinded through 26 weeks, we have requested the DSMB to provide a comment on suicidality. We believe that these data, if positive, should provide investors with further clinical validation of COMP360's treatment potential in TRD. The second Phase 3 trial, COMP006, which has three active arms could further define the COMP360 profile with data on a second initial treatment, which we believe could potentially extend durability or deepen response. Enrollment is going well in 006, and I'll remind you that, that is a global trial, and we're on track for the 26 week results in the second half of 2026. Also during this quarter, 52 week safety and efficacy data from the COMP004 study was published in the Journal of Clinical Psychology. This was an observational 52 week follow-up…

Thank you, Kabir. After our January financing, we are in a very strong financial position. At the end of March, we had cash and cash equivalents of $260 million, which we expect to fund our operations at least through the planned 26 week data readout from our second Phase 3 trial, COMP006, which is expected in the second half of 2026. This compares with $165 million at the end of 2024. Debt under the Hercules loan facility was $30.5 million at the end of the first quarter. Cash used in operations for the first quarter was $45.7 million and we expect net cash used in operations for the full year 2025 to be within the range of $120 million to $145 million. Again, as Kabir said earlier, we eagerly await the results of our first Phase 3 data as we know you're waiting for it as well. As a reminder, this is the first of three expected data readouts from this program over the next 18 months. Based on our data to date, including the recent 52 week follow-up data from our Phase 2b trial, we believe COMP360 could represent a clinically differentiated treatment option that is rapid acting with the potential for paradigm changing durability. We also continue to work toward a final design for our late stage clinical program in PTSD and look forward to updating investors when that design is finalized. Given the high unmet need and limited current treatment options, we see a significant commercial opportunity in PTSD. With that, we're going to move to Q&A. And as a reminder, Dr. Guy Goodwin and Dr. Steve Lavine are also with us today for the Q&A portion. And with that, let me turn it back over to the operator.

[Operator Instructions] Your first question comes from the line of Leonid Timashev of RBC Capital Markets.

This is Kevin on for Leonid. So you recently, as you mentioned, published longer term follow up data from the Phase 2. Maybe can you just highlight the key takeaways in your view on durability as well as what you may have learned about which dose is most appropriate?

I'll hand actually to Guy to take the lead on that then, please.

I mean, Kevin, this data is not as complete as we would like it to have been. So I'd like to start with that disclaimer really. It's not a definitive study, a definitive follow-up study by any means for various reasons. But what it does show is a difference between the durability of the three doses. This is most clearly seen in the subgroup who completed the study. And they, as we mentioned earlier, are a little unrepresentative, but nevertheless they did demonstrate some patients who received 25 milligrams can last as long as six months following treatment. And that is much less likely in people who've received lower doses. So I think it reiterates our conclusion from the Phase 2 study that 25 milligrams is, for the time being, the preferred dose that we think, which should carry forward and will be the one that we obviously used in the Phase 3 program.

Next question comes from the line of Paul Matteis of Stifel.

I mean, obviously, with the top line disclosure and your guys' conservatism around trying to not bias the 006 trial, it's going to be difficult to compare across studies, which is totally reasonable. But just as it relates to thinking about the actual efficacy delta on MADRS, one challenge in the psychodelic space is just a high degree of variability and placebo effect across trials. What is your base case -- again, the study is blinded, but what was your base case and what the placebo effect might be in this study? And how might that kind of inform the way we contextualize this effect size versus what others have observed?

I mean we -- our estimate, our guesstimate, I think you'd have to call it, was really based on what we saw in a previous study of NDD from Switzerland, which was with COMP360. And looking at our own data, our own data, obviously was from an arm, which received 1 milligram. So we considered whether or not patients in that population had a psychedelic experience or not or anything approaching a psychedelic experience. And so we took account of the subgroup who seemed to us to have the lowest experience and looked at their responses in estimating what the placebo was likely to be. I think in this field, we generally expect to see in well conducted trials a placebo response. The placebo arm does not receive nothing. They receive a great deal of attention, have frequent hospital visits, it's construed in a very positive way by patients. And so you would expect a placebo response, you would respect -- expect also regression to the mean. So the normal expectation is for there to be a placebo response. And obviously, the difference you see between placebo and the active arm can be attributed to the effect of the drug, which is the key thing that we're wanting to prove. And as we've indicated, we would be very pleased to see effects of over three on the MADRS scale. We think that is clinically significant, anything above that is a bonus.

And if I could ask one follow-up question just on the DSMB commentary on the presence or lack of a suicidality signal. Ultimately, I guess, where do you think you guys or the DSMB might draw the line between an actual signal and noise, right? Like I would imagine two events versus one event could be kind of codified as noise. But is there any -- I guess, to the outside looking at it seems like there's an art to this, there's an element of subjectivity. How should we interpret that?

I mean that is a practice of medicine question really, because what the -- we're asking the DSMB to do is to take a judgment that is based, not just on the current event and the relative frequencies, but also the severity, the timing, the way in which the event evolves and may, in fact, resolve. And all of those factors, I think, weigh, and if I were doing the job and I have in the past for a company, that would weigh in how I reported the likely probability that there was an imbalance in the two arms, which is what we're asking the DSMB to do. So it's a nuanced judgment. It cannot be done on the basis of the scale. It can't be done on the base of numbers. It has to be done on the basis of a complete assessment of the picture for each of the individual instances.

Next question comes from the line of Charles Duncan of Cantor Fitzgerald.

I wanted to ask another question about suicidality. And I'm kind of wondering if, back when you were designing this study, was that something that the FDA was more concerned about or were you hearing concerns or thoughts about that from the broader, call it, investment community? And what is the background rate that you were considering when conducting the study given this TRD population?

The issue of suicidality was not addressed directly or brought up by the agency in our discussions with them. Suicidality is a core feature of depression. All trials of either MDD or TRD have to include patients with some degree, either a history of suicidality or current passive suicidality to exclude it as a factor entirely is simply to distort the population in a way that it ceases to be representative of the target population. So suicidality is a fact that everybody has to contend with in designing and executing these studies. It arose as an issue, as you may remember, after we released the data from 001 and the fact that we had an imbalance in the number of behavioral actions related to suicidality, all of them somewhat delayed from the actual treatment, that -- and the 25-milligram arm, that produced a good deal of commentary and seems never to have left us. So we live with this continues and that is obviously something we remain seriously concerned about. We wish to monitor carefully in the Phase 3 and to generate the numbers that will give us confidence about the actual potential for differences between the three arms. Our expectation is that there will not be important differences between the three arms.

Just to build on both guys points together, Charles. Even in the light of the 2b data, the FDA was still not concerned about the likelihood of [indiscernible] Phase 3, they fully understand that this is a core feature of the disease.

Makes sense, looking forward to that data. A quick question for Steve on HealthPort in terms of that recent collaboration. I guess I'm wondering if you could characterize in any way the current delivery of esketamine or Spravato that HealthPort is involved in? If you can quantify that in any way, so we get a sense of how involved they are in the field?

So first just as a reminder, part of the efforts with creating this network of collaborations is for them to reflect the broad array, the spectrum of where meta healthcare is delivered in this country. Within the existing collaborations, we did not feel there was adequate representation of sites that serve underserved populations, and HealthPort is a very high quality example of a certified community behavioral health clinic that specifically addresses the unmet needs in marginalized and underserved populations. There are some assumptions that I think are common that community based mental health clinics are not able to deliver newer or more innovative treatments. And it is the fact that HealthPort has been able to deliver Spravato to patients, esketamine, and are highly motivated to make sure that there is not a widening of existing health care disparities and a lack of access for their population if new treatment options are approved. And so they have some experience already with interventional treatments and are excited about and motivated to be operationally ready to deliver new treatments if approved. And important also to note that inherent within the CCBHC model, certified community behavioral health clinics, is the sharing nationally across that system of best practices and learnings and HealthPort has also historically been a leader there, particularly with disseminating their social determinants and health model.

Your next question comes from the line of Ritu Baral of TD Cowen.

This is Athena on for Ritu Baral. Given the potential pharma tariffs, can you provide additional color on your manufacturing supply chain and whether there has been any FDA inspection of your manufacturing centers?

So yes, currently, product is manufactured in the UK. We have always planned and are working on plans to add an additional manufacturing capability in the US for commercial supply. So those plans were already underway and we are moving on those. These are sites that have extensive experience of manufacturing, not just for us but our very well established CDMOs for a wide range of pharmaceutical manufacturers, so have had multiple inspections over the years.

Do you have a time line on the additional US sites?

Not at this point. But as I say, we are working on that. That was already in the plan and in our forecast for the next couple of years ahead of potential commercial supply.

And Athena, it's probably worth mentioning that from a manufacturing perspective, compared to other biotechs or pharmaceuticals, this is a pretty straightforward process and a pretty small quantity of material. And so it's not really at the top of our minds in terms of risks, we're mitigating any risks we have. But as Kabir mentioned, as we near commercialization that is currently the plan.

And clearly, this is a typical small molecule. So in terms -- since we haven't yet established a price, if, in fact, there was a tariff element on any cost of goods, we would clearly be able to consider that in selling a price in due course.

Your next question comes from the line of Vikram Purohit of Morgan Stanley.

This is [Parth] on for Vikram. Just one question. Could you provide the current mix of color on patients enrolled into COMP006, like how similar or distinct is this patient profile that was enrolled in the Phase 2b?

Essentially, the criteria for recruitment of the same, we are not continuously monitoring the actual baseline characteristics. I mean, we're remaining blind to the subset -- to the data but we know that we're recruiting patients using the same criteria. So there's really no reason why they would be any different.

The only thing which we have stressed repeatedly in the Phase 2b, the actual percentage with prior psychidetic experience was 6%. In the Phase 3, it's after the 15%. And while we don't, to Guy's point, know the exact, we can assume it is around that percentage in the 005 study.

And then just one more quickly. What are your current thoughts on BD specifically with regards to like a large pharma partner, is this something that you guys would be interested in? And if so, when could this make sense?

So we are clear that we believe we're doing something unique. And if approved, what we have is paradigm breaking transformational for the treatment of serious mental illness. And our commitment is to do that ourselves in the US if we can, and potentially some other select geographies at the moment. So from our perspective, COMPASS is set up to commercialize COMP360, if approved, and to build from there. And I have no particular comment on big strategic intent at this point.

Your next question comes from the line of Sumant Kulkarni with Canaccord Genuity.

Also a question on suicidality risk. What do you think is an optimal time to pass before suicidality might not be attributable to a single dose of COMP360? And how much you prepare for imbalances in nonresponders to COMP360 because of the potential unblinding given the nature of the product?

That's actually quite a tough question. I think my answer is really that we'll look and see what the data shows us, to be honest. I don't think predictions are in order here. That's rather a poor answer to your question, but I think that's the way I feel about it.

Just a quick follow-up. Have you seen any changes within the FDA for anyone that might be considered a champion of psychedelic therapeutic approaches in your interaction so far?

Thus far, we've seen no changes in our interactions with the FDA, which in the last couple of months have been largely routine around event reporting and so on. Clearly, we're tracking like everyone else, some of the changes higher up in the hierarchy, not only within the FDA but higher up than that. As we've said before, we see that potentially producing some favorable tailwinds for us. But at this stage, nothing has changed around our day-to-day interactions with the agency.

Our next question comes from the line of Patrick Trucchio of H.C. Wainwright.

First, just regarding the COMP360 TRD program and the 52 week observational follow-up study. I'm wondering how we should interpret those data in the context of your pivotal program or in the potential commercialization of COMP360 in TRD? And then also in the pivotal TRD program, is there tracking or use of antidepressants or other psychotropic medications post dosing the trials, and how might that inform your durability or safety analyses? And then separately, I'm wondering regarding PTSD, have you initiated regulatory interactions around PTSD program design? And if so, what feedback have you received?

Steve, do you want to comment first on the durability and how that feeds into how we think about commercialization?

I'll start there. Guy may want to jump in with the other part of the question related to the starting of other treatments and the inoperability of the data as we get further into the study. But specifically on durability and to your question about what we learned from that long term extension, I think called 004 and how we will look at durability within the Phase 3 program. As was mentioned during the opening remarks, there were some limitations as far as the interpretability of the long term study just because it wasn't the full patient population that continued. However, when looking at all 233 patients from that study included in the primary analysis that did give a very strong signal of durability at least to 12 weeks. And then for those who did continue into the long term extension study and were followed out to 52 weeks, response up to six months. Now in Phase 3, of course, we'll be reporting initially the six week data. And frankly, durability even to week six in this population, given the limited options available today is already a shift in the paradigm. That already would be of tremendous value to patients, to healthcare providers, psychiatrists and others. We will be looking at durability, of course, beyond six weeks, blind it out to week 26 and then we'll have continued opportunity to look at durability in the open label portion probably 26 to week 52. And so we'll have to see what we see there. But again, even with the initial data we have, durability up to six weeks would be really groundbreaking in this area.

So the impact of antidepressants and…

Use of antidepressants and the interpretation of…

I think that the key thing in practice will be that antidepressants are going to be part of the picture for the treatment of these patients. I'm not sure that really it affects -- the key for the patient is to remain well. We're going to see the addition of antidepressant treatments. We can look at that post hoc within the trials. But I think in ordinary practice, we'll expect to see a lot of co-administration. We await obviously proper data on this but I think you have to anticipate that, that will -- they will pay a part of long term treatment in these patients.

And maybe worth saying that it does land a real world element to the latter portions of these studies, because that is quite common in clinical practice for patients to be on multiple treatments simultaneously, often to continuing antidepressant in the background while they're trying other options. In most cases, the reason why they're trying new treatments is because those background treatments have not been particularly effective. And in some cases, it's just the comfort of being on something. So as Guy said, the trial is designed for us to particularly in the beginning of the study, differentiate and fully characterize the profile of our drug effect. But it is the likelihood that patients will resume some treatments and that will give us an opportunity to better understand what real world practice may look like.

And on PTSD, Patrick, we will be reviewing and discussing those plans with the agency. But as you'll recall, we choose not to give specific feedback on what our discussions are with the agency.

That concludes our Q&A session. I'd now like to hand back the call to the management.

Thank you very much. So thanks, everyone, for your time and attention this morning. I think to state the obvious, we are very eagerly awaiting data next month. We know that you are as well. But we remain confident in that data, in that first six week primary endpoint readout of 005. And we continue to make very good progress on recruiting in 006 as well and reconfirm the time lines for that for data in the second half of 2026. So with that, thank you, and we look forward to pressing on and executing and potentially bringing forward a paradigm changing treatment for TRD. Thanks, everyone, and have a good day.

Thank you for attending today's call. You may now disconnect. Goodbye.