COMPASS Pathways plc (CMPS) Earnings Call Transcript & Summary

Good day, ladies and gentlemen, and welcome to this COMPASS Pathways update webinar. [Operator Instructions] As a reminder, this call is being recorded. I would now like to introduce your host for today's call, Stephen Schultz. You may begin.

Welcome all of you, and thank you for joining us today for this webinar. My name is Steve Schultz, Senior Vice President of Investor Relations at COMPASS Pathways. The call is being recorded and will be available for 30 days -- I'm sorry, the call is being recorded and will be available on the COMPASS Pathways Investor Relations website 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 statements about future plans and prospects that constitute forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement, including those risks and uncertainties described under the heading Risk Factors in our most recent filings with the U.S. Securities and Exchange Commission. These forward-looking statements represent our views only as of today, and we specifically disclaim any obligation to update or revise any forward-looking statement even if our estimates or assumptions change. I'll now hand the call to Kabir Nath, Chief Executive Officer of COMPASS Pathways.

Thank you, Steve, and thank you all for joining us. During today's program, we'll be updating you on both our COMP360 programs for post-traumatic stress disorder or PTSD, and for treatment-resistant depression, which we'll refer to as TRD hereafter. Today, we announced our pivotal Phase IIb/III PTSD trial design. PTSD is an even larger patient population than TRD with an estimated 13 million individuals that suffer with this condition in the U.S. Like TRD, there are very limited therapeutic options with no new medicines approved in PTSD in decades, and we believe COMP360 has great potential in this population. Guy will provide a physician's view on the unmet need in PTSD, and Mike will walk you through the trial design. We'll then turn to our commercial preparedness for potential TRD approval. TRD is a difficult condition to treat. Any treatment that demonstrates clinically meaningful efficacy and is well tolerated has the potential to address the estimated 4 million patients in the U.S. alone. We're pleased today to have Dr. Gary Small, Director of Behavioral Health Breakthrough Therapies at Hackensack Meridian Health join us. Dr. Small will provide his thoughts on this condition and what a new treatment option like COMP360, if approved, would mean for patients. Of course, our network of treatment centers ready, willing, and able to deliver COMP360 if approved, is essential. Steve will discuss how COMP360 compares to the only medicine that's indicated and actually used today in TRD, esketamine, under the brand name Spravato. As part of this discussion, Steve will host a roundtable with three of our strategic collaboration partners about how they anticipate seamlessly integrating COMP360 into their offerings. We have made excellent progress in our TRD program. We've completed a roll out ahead of schedule in our 006 trial, our second Phase III trial, and we've seen openness by the FDA to a rolling submission and review. Based on these developments, COMPASS has significantly accelerated our launch time lines. We will be launch ready by the end of this year. And Lori will give us an update on our commercial readiness. So with that, let me begin by handing to Guy to discuss PTSD.

Thank you, Kabir. In the next few minutes, I'll outline the critical unmet needs in treating PTSD and the compelling clinical rationale for advancing a new development program for COMP360 psilocybin. Let's dive in with the first slide. First, what is PTSD? It's a debilitating mental health condition triggered by experiencing or witnessing a traumatic event, which could be combat, assault, disaster. Symptoms include intrusive memories often as vivid unsettling flashbacks, hypervigilance and irritability, avoidance and emotional numbness or negativity. Their persistence can profoundly disrupt daily life, relationships, and work. According to recent data, PTSD affects over 6% of the U.S. adult population in their lifetime with higher rates among women translating to millions grappling with this condition in the U.S. and around the world. The human cost of PTSD is immense. It appears to lead to higher rates of substance abuse, depression, and suicide, 4x to 6x the general population risk. Overall, the U.S. economic burden from lost productivity and healthcare has been estimated at $230 billion. That's $0.25 trillion per annum or the equivalent of the annual GDP of a middle-sized national economy. 82% of these costs are attributable to civilians and 18% to military personnel and veterans, but the annual cost of PTSD per person is proportionally higher for military and personnel veterans. Compounding this burden of disease, current treatments fall short. The gold standard of an evidence-based psychotherapy can help but requires intensive sessions over weeks or months. Access to such treatments is often limited. In addition, for trauma-focused therapy, dropout rates often due to the emotional toll of reliving trauma can exceed 30%. It's also important to notice that on the pharmacological side, despite significant efforts, only two FDA-approved medications exist, sertraline and paroxetine. Both SSRIs and both approved for PTSD over 25 years ago. These antidepressants can reduce symptoms, but full durable remission is unusual. In addition, they are not necessarily well tolerated. Side effects like sexual dysfunction, weight gain, and sedation may be distressing in their own right and lead to poor adherence to treatment. PTSD appears to involve dysregulation in brain circuits involving the amygdala, hippocampus, and prefrontal cortex, which can be read over to the observations of impaired fear extinction and hyperarousal. The comorbidity and the potential underlying biology suggest a close association with major depression. Thus, the efficacy of the SSRIs, which primarily modulates serotonin in both PTSD and major depression provides an additional pharmacological link. Therefore, the positive effects of serotonergic agonists like COMP360 psilocybin in treatment-resistant depression could also translate to PTSD. Psilocybin offers a novel potential mechanism with the possibility of durable changes in emotional processing that can underpin more complete clinical responses. Our preliminary work with COMP360 psilocybin indeed demonstrated both the -- pardon me, possibly a durable change in emotional processes. Our preliminary work with COMP360 psilocybin indeed demonstrated both the necessary tolerability and a rapid resolution of the core symptoms of PTSD after a single dose with sustained responses lasting for up to 12 weeks. The unmet needs in PTSD, limited treatment options, insufficient efficacy with incomplete symptom relief and the long absence of innovation demand bold action. The clinical rationale is clear to leverage advantages in the clinical understanding of psilocybin and create a more beneficial treatment option, providing faster and more durable symptom relief without the undesirable side effects seen in currently utilized medications. We at COMPASS Pathways are prioritizing a PTSD program that will bring hope to millions of patients and their families. Thank you. Let me now hand over to Mike Gold, our Chief R&D Officer, to go through the details of our PTSD program. Mike?

Great. Thank you, Guy, and thank you all for the opportunity to talk about our PTSD study for your time and for your attention. The COMPASS Pathway team has created a very strong and well-designed study. And today, I want to give you a brief background on our PTSD program, where we are, how we got here, our study design and next steps. As Guy referenced, and you can see on the screen, COMPASS completed and reported an open-label safety and tolerability Phase II study in 22 patients with PTSD, which was conducted across multiple sites in the U.S. and the U.K. It tested a single dose of 25 milligrams of COMP360, which is our proprietary synthetic formulation of psilocybin in patients with PTSD, obviously. The study detected a large benefit in the CAPS-5 score, a benefit that was sustained through week 12, which was the end of the study. And you can see on the graph on the slide, the change from baseline in the -- from the study. On the basis of the efficacy signal that we saw in this study, the overall clean safety profile of the study with no serious adverse events observed and supported by the data that we were accumulating from our own treatment-resistant depression studies, we felt there was a very good potential to address the huge unmet medical need in PTSD that Guy just described. We aimed to come up with a study design that would allow us to maximize the chances of getting an approval with a single trial, and to stay within the rigorous scientific approach that we've developed with our TRD program. So where are we now? We've agreed on the design after meeting with FDA and taking into consideration their feedback. And as you heard earlier today, our IND has been accepted by the FDA. So let's wait. Let's see the next slide come up. So there we go. As you can now see on the slide, this is the finalized design. It's a 3-arm Phase IIb/III study, which will test two doses of 25 milligrams as a target dose compared to 1 milligram as the active control. We're using a smaller population of patients at 10 milligrams to help address the questions of functional unblinding, similar to what was done in our Phase IIb and our Phase III COMP006 TRD studies. Similar to our Phase III COMP006 study in TRD, we will use a two-dose paradigm for PTSD. Our belief based on prior studies of COMP360 is that more than one dose of a classical psychedelic is likely to be the best approach to maximize benefit. The primary endpoint for this PTSD study is the CAPS-5 at week 8. CAPS-5 is the standard instrument used in PTSD studies and measures a range of different aspects of the condition. A key secondary outcome is the PCL-5, which is another PTSD checklist to measure other elements of the PTSD syndromic picture. We're also collecting other secondary measurements to understand depressive symptomatology and anxiety and to get a broader and more holistic view of the drug's benefit. Obviously, we're also evaluating safety. Part A is a controlled double-blind randomized 12-week portion and will include the two doses of COMP360, 4 weeks apart. Part B is an open-label portion and will run 40 weeks, so for a total of 52 weeks in the study. Similar to our TRD studies, participants who are nonresponders or those who are remitters and then later relapse will have an opportunity for another dose in Part B. We will also be assessing safety in this study similar to our TRD trials, and we will make use of an independent data safety monitoring board to monitor both blinded and unblinded data. As is the case with our TRD program, we will be conducting the study to the highest standards and align with the FDA guidelines for psychedelic treatment development. We've selected a CRO. We are now in the process of selecting sites and investigators for the program, and we expect to start screening patients this quarter. As a physician, it is truly a privilege to have the opportunity to address such significant mental health challenges. That is the program right now for PTSD. And now let me turn to a little bit on treatment-resistant depression. As a preface, let me first discuss the significant unmet medical need in TRD. Today, approximately 23 million adults experience major depression in the U.S. Of those, we estimate that about 4 million are failed by two or more MDD indicated products. And with only two drug treatments approved for TRD and generally only one that is utilized, the challenge to bring safe and efficacious option to patients is significant, and this is our focus. With that, let me introduce you to Dr. Gary Small, who will provide his perspective on the treatment landscape. And thank you again for your attention. So Dr. Small is a Director of Behavioral Health Breakthrough Therapies at Hackensack University Medical Center, one of our collaboration partners. He has extensive experience with TRD and with a variety of interventional treatments, including Spravato. And with that, Dr. Small, the meeting is yours.

Thank you, Michael. I'm going to be talking about unmet needs and the treatment landscape for TRD. Next slide, please. Just to begin my potential conflicts of interest and disclosures. Next slide. So with TRD, the general consensus for definition is that these patients have an inadequate response to two or more antidepressants despite adequacy of treatment and adherence to treatment. And this accounts for about 1/3 of patients with major depression. And we heard earlier that it affects about 4 million people in the U.S. If you look at the worldwide prevalence, it's estimated 100 million people. But it's not only the numbers. It's the direct and indirect costs. It accounts for more than half of these costs of major depression. So it's not surprising that it leads to significant personal, familial, and societal burdens. Next slide. So if we take a moment to look at the current treatments used for major depression and TRD, with major depression, as we know, most of these treatments are based on monoaminergic mechanisms, affecting serotonin, norepinephrine, and dopamine. And there's been limited innovation in this space. With TRD, most of the strategies are ineffective and they're inefficient, and what we generally do is to extend the treatment of the antidepressant, combine it or switch it, or use psychotherapy. It requires daily chronic use with the medications. And of course, this imposes ongoing side effect risks. If we use neuromodulation in these cases, that treatments like ECT or electroconvulsive therapy or transcranial magnetic stimulation, that brings up issues of accessibility and tolerability. Next. So what about the management of TRD? Let's look a little bit more at the data on that. If we extend antidepressant trials, systematic review of the available studies on response after 4 weeks indicates that about 20% of patients respond during weeks 5 to 8, and only 10% respond during weeks 9 to 12. Now depressed patients, they prioritize rapidity of antidepressant action. When you're depressed, you want to feel better. It's really debilitating. You want to feel better now rather than later. Despite that, it's a big problem. These people are reluctant to get into these prolonged trials. What about switching antidepressants? If you look at the meta-analysis on the data available, it's conflicting as to whether switching antidepressants increases the likelihood of response or not. With combining antidepressants, you run into the problem of polypharmacy, which increases the risk for drug-drug interactions and further side effects. And actually, there are a few relevant studies that have been conducted in this population to show that this is effective despite the fact that doctors often use this approach. Next slide. Let me hand it off now to Steve Levine.

Thank you, Dr. Small. Sorry for the delay. I'm Dr. Steve Levine, Chief Patient Officer. And in this segment, we'll be discussing what we believe are the key clinical advantages of COMP360 psilocybin treatment compared with the current standard of care for TRD based on the developing profile from data to date. We'll give an overview of the existing therapeutic landscape, the limitations patients and clinicians currently face, and discuss how the emerging profile of COMP360 potentially represents a meaningful advance both clinically and commercially. Having founded a national interventional psychiatry network 15 years ago and being one of the first networks to prescribe Spravato when it launched, I'm intimately familiar with the challenges and opportunities of providers and patients, and I'm passionate about leveraging my prior experience to help launch and scale COMP360, if approved. To understand where COMP360 potentially fits, it's important to start with the current pharmacologic landscape. As said before, for MDD, there are more than 50 approved pharmacologic treatments. These therapies are daily chronic treatments. They require consistent adherence, yet they bring daily side effects. And when studied in TRD, they have failed to prove efficacy. This leads to a paradox in clinical practice. While existing treatments may help some patients, many patients are expected to continue in long-term treatment with medications that aren't providing relief while accumulating the risks and side effects associated with ongoing exposure. When we narrow the focus specifically to TRD, which is defined as patients who have been failed by 2 prior treatments, the picture becomes even more constrained. While numerous MDD agents are used after failure of first or later line treatments, we have only two approved products explicitly for TRD with proven clinical efficacy. And in practice, only one is commonly prescribed, Spravato or intranasal esketamine. Spravato has proven to be commercially successful despite operational and economic challenges for healthcare providers and significant burden to patients and their caregivers. Its administration requires numerous 2- to 3-hour appointments. Dosing is twice weekly for the first 4 weeks, meaning 8 treatments in the first month alone. This is followed by weekly dosing in weeks 5 through 8 and then ongoing weekly or biweekly maintenance, leading to 25 to 35 treatments per year or more. Patients cannot drive themselves home, so the burden of treatment frequently also falls to caregivers. And for patients and caregivers, they are unlikely to return to work that day, so a day is a day. The frequency of these logistical demands significantly limits adoption and adherence even in motivated patients and imposes substantial operational burden on clinics. Another important constraint is that there are no dedicated current procedural terminology codes or CPT codes, which are the codes submitted by providers for reimbursement of medical services that adequately reimburse providers for the monitoring and clinical time required for Spravato treatment. Providers use general evaluation and management codes that do not fully capture all of the work performed and the practice expenses required. Within a day, they must schedule 2 to 3 patients for a room to be fully reimbursed for the day. Turning the room over multiple times requires cleaning and paperwork for multiple patients, adding cost and operational complexity. And during the time in between patients, that room is not being paid for, creating gaps in reimbursement for the room. The economics are more favorable for patient occupying that room all day versus 2 to 3 patients for 2 to 3 hours each. COMPASS learned from some of the challenges of the Spravato launch and designed new CPT codes specific for psychedelics that capture the full cost of treatment, monitoring and practice expenses and can be reimbursed on an hourly basis. So for COMP360, the full 6 to 8 hours could be reimbursed, filling the gaps in reimbursement that practices currently have between patients for Spravato and minimizing the administrative burden of multiple patients in a day. These CPT codes are already approved and are ready for providers to use once COMP360 is launched. This is an essential step towards enabling scalable clinical delivery and appropriate reimbursement for providers. There are now more than 6,800 interventional psychiatry centers delivering Spravato. But despite all of this, there is currently no treatment in TRD that offers both rapid and durable symptom reduction. This is a major unmet need, both for patients and for the healthcare system that supports them. Against this backdrop, COMP360 presents an emerging differentiated profile that may address many of these limitations. Our Phase IIb data, together with top line results from the 005 Phase III study demonstrate two critical features: one, immediate robust response; and two, durability of that response after a single dose. In fact, in the 005 study, a single administration of COMP360 showed an effect size at week 6 that is comparable to the effect size of Spravato, which requires 10 treatments to get to 6 weeks. So what we've already seen to 6 weeks could be paradigm changing in practice. Sustained efficacy following a single administration that may be deepened by a second initial administration as being tested in 006 represents a fundamentally different treatment paradigm for TRD. Safety is equally important. In Phase IIb, most adverse events were mild to moderate. They generally resolved the day after administration and treatment adherence was 100% since it was a single dose. For those who have been distracted by multitasking, here are five key takeaways. First, Spravato, while approved, requires frequent dosing to maintain treatment effect and can be highly burdensome to both patients and their caregivers. Second, there is currently no existing drug treatment indicated for TRD that offers both rapid onset and durability. Third, COMP360's emerging profile across efficacy, durability, safety, adherence, and patient experience positions it as a potentially transformative treatment option in TRD. Fourth, the current interventional psychiatry treatment center infrastructure is already set up to support new multi-hour treatments like psychedelics. This includes an available and trained workforce, operational know-how and rapidly growing capacity. And importantly, CPT codes specifically designed for monitoring psychedelic treatments means that provider economics will not be impacted regardless of treatment time required. As we look ahead, these clinical advantages form the basis for a compelling opportunity to set a new standard of care for patients who have not found relief with existing options. And what better way to begin to understand the treatment delivery landscape than to hear directly from three of our strategic collaboration partners that are currently delivering interventional psychiatry treatments, including Spravato. We are pleased to have with us today Dr. Geoffrey Grammer, Chief Medical Officer of Greenbrook Neuronetics. With over 90 sites in the U.S., Greenbrook is one of the top providers of Spravato. Myriam Barthes, Co-Founder and CEO of Journey Clinical, which operates a decentralized network of thousands of therapists supported by a central medical team, delivering ketamine-assisted therapy and Spravato; and Dimitri Cavathas, CEO of HealthPort, a Maryland-based certified community behavioral health clinic or CCBHC, that provides comprehensive care to underserved populations. Thank you all for being with us today. I have a number of questions for the group. So let's go with a fireside chat format.

To start, and this is a question for each of you. Can you please briefly share an overview of your organization and the approach you take to treating patients with TRD. Let's start with Dr. Grammer, and then Myriam and then Dimitri.

Thank you, Steve, for that. I appreciate it. So Greenbrook Wellness Center, which is a subsidiary of Neuronetics, we've been in this treatment-resistant space since 2011. And we currently operate 95 centers. On any given day, we will do 800 TMS treatments and we will do 400 Spravato treatments. We remain committed to being able to leverage new modalities and technologies to helping patients who have not gotten adequate relief from either medications and/or psychotherapy. We are positioning ourselves now to continue to plug in new modalities such as COMP360 into our armamentarium to try to help patients. And our whole philosophy is overcoming barriers to care, including awareness, geographic proximity, and fiscal viability.

Thank you, Dr. Grammer. Myriam?

Today, Journey Clinical is the leading care delivery platform and marketplace for FDA-approved psychedelic informed care. Our platform gives licensed therapists, everything they need to deliver these treatments in their practice, including access to a medical team, education, insurance, and community. Through our unique collaborative care model, we partner with over 3,000 therapists to help patients who suffer from depression and anxiety with insurance covered ketamine-assisted psychotherapy, Spravato and medication management. So far, we have delivered about 500,000 hours of treatment, and given the rapid antidepressant effects of ketamine alongside therapy pre and post treatment, we have successfully treated thousands of patients with TRD.

Thank you. And Dimitri?

Thank you, Steve, for having me here. Honored to be here. HealthPort is a rural safety net health and housing provider, providing behavioral healthcare and primary care for the lower Eastern shore community in Maryland. And at any given time, we served about 2,000 people in 4 counties with significant health professional shortages as well as a disproportionate number of people on Medicaid and Medicare. For 45 years, our organization is providing a full continuum of support services to individuals with psychiatric and addiction issues as well as disabilities and other disadvantages. We have a unique platform with social determinants of health interventions, which allows us to offer a variety of programs, tailor people's needs and in particular, the kinds of issues that need to be addressed with treatment-resistant depression.

Amazing. I think we can see that this group represents really the gamut of where people with TRD receive their care today, including those who are historically underserved. So maybe coming back over to Dr. Grammer, you're not only the Chief Medical Officer of Greenbrook, you're a practicing psychiatrist who cares for TRD patients everyday. So I'm curious, what you're seeing as far as awareness and interest in psychedelic treatments from your patients that are currently receiving Spravato and TMS?

Yes, absolutely. It's a great question. And I don't think I can overstate the enthusiasm, to be honest. What I have seen in the 30 years that I've been doing psychiatry is there have been a few pivotal moments of paradigm changes. One of those was when TMS was initially cleared by the FDA back in 2008. The next one was when Spravato received FDA clearance, and COMP360, in my opinion, is the next large paradigm change. But in some ways, it has more enthusiasm than those other two modalities for several reasons. I think one is more practical where for decades, we had antidepressant medications and therapy as the cornerstones of treatment, and patients became acclimated to that expectation. So when we had new treatments that were fundamentally different, it took a while for people to kind of accept that. That barrier, I think, we've broken through. But the other thing fair or not is that there is a romanticized enthusiasm for COMP360. And what I will tell you is people struggle with their own sort of existential negotiation. They struggle with their meeting of life, so to speak. And the psychedelic therapies have this idea that not only do they provide symptom relief, but for some patients, they may provide awareness. And so what I'm seeing is an outsized enthusiasm. I mean, I do 32 hours a week of clinic. And most of the patients I treat get better with modalities they have. But even in those patients currently receiving Spravato or TMS, they are asking me, when is psilocybin coming? When is psilocybin coming? And I think it's because they want some of those answers. They want that durability. They want that quick relief, and they want to feel that sense of peace. And I don't think it's a question of, if there's going to be a demand. Quite the opposite, I think it is how well we are going to meet that demand. One of the statements I give is we will have a line out the door of enthusiasm. Every day, I'm hearing patients asking about this, begging for it, wanting to be first in line. And so for the listeners out there, in my 30 years of experience, this is very different than anything that has preceded it.

Well, those are some great points and really sounds like a call to action. So thank you for that. Maybe turning to Myriam. Having described the model of Journey Clinical, which is certainly a very different model perhaps than Greenbrook or HealthPort, how do you see COMP360 fitting into your organization?

At Journey Clinical, we are definitely ready, willing and able to deliver COMP360 within our decentralized care model. In fact, I would really almost add that in the last 4 years, our clinicians have already been delivering psychedelic-informed care with ketamine therapy and more recently also with Spravato. So if I give you an example, today, patients would go through a medical intake to determine treatment eligibility. And if they're eligible, they receive a prescription. Then they would follow traditional follow-up consultation with our medical team to monitor outcome. And what that means is we have already built end-to-end protocols, closed-loop safety mechanism, outcomes tracking as well as insurance coverage. So we would very simply adapt our protocol to the drug profile of COMP360. In addition to that, we would go beyond the REMS and follow the preparation, dosing, integration clinical framework. And what would happen in this case is that similarly to the way we deliver Spravato, dosing session would happen in therapy practices with monitoring and support. And while there is no active therapy during dosing session to enable patients to self-direct the work, we would provide continuity of care with psychotherapy pre and post treatment through our network of licensed mental health professionals. In the real world, truly, this model has already enabled us to scale ketamine therapy and help patients with symptom reduction, followed by deep therapeutic healing and emotional changes.

All right. Well, it sounds like Journey Clinical and your network members are chomping at the bit, so we better hurry up. Dimitri, I haven't forgotten about you. As you know, at COMPASS, we're committed to broad and equitable patient access. Historically and sadly, innovation in healthcare has often widened existing access disparities. I know you're optimistic about adoption of COMP360 by HealthPort and the nation's 500-plus CCBHCs. Can you talk a little bit about the potential you see?

Yes, Steve. Thank you so much. This is really about equitable access to the COMP360 intervention. And the safety net providers of the certified community behavioral health clinics really have a platform and an ability to educate people that are usually disenfranchised, do not have great access to care. And that is -- our job is to educate them. And this is what we've learned with Spravato. We've had a really great ability to learn from the use of Spravato in a rural environment and in an environment where people don't normally have really good access to treatment. And the biggest fear of a COMP360 intervention is that only people with good insurance and or high net worth individuals will be able to access this. And this is something we want to change. Our model of care as a certified Community Behavioral Health Clinic allows us to create a structure, a cost structure to provide this intervention across the country. Currently, there's over 500 CCBHCs in 46 states, D.C., Puerto Rico, and Guam, serving over 3 million people. So this is an ability for these CCBHCs have amazing expertise, amazing knowledge, and an ability to engage this community to get this very, very important intervention.

Amazing. You always get me fired up, Dimitri. That's exciting. So Dr. Grammer, you talked before about the need that you're seeing in the patient population you're treating today, the patients that you see every day, and some of the awareness and the enthusiasm. Can you talk a bit about how a large organization like Greenbrook that currently delivers a lot of Spravato and TMS, how do you see COMP360 fitting into Greenbrook?

Yes. So we are all hands on deck when it comes to getting ready for COMP360, right? So at Greenbrook, we have the full continuum of care all the way from marketing for making that awareness available to patients to call centers that will instantly answer the phone and then lead to conversions into appointments and treatment starts and then all the way on the back end where we have the relationship with payers, and we're able to file those claims and get reimbursement so that we utilize people's insurance so they can have access to that care without necessarily being financially overly burdensome. In addition, at our 95 centers, we've got square footage specifically dedicated to Spravato. We don't do the end of the hallway kind of like plastic chair kind of thing. We actually have dedicated rooms with subdued lighting and comfortable accommodations, close bathroom, the whole nine yards. And what we've been doing is in preparation for this, we're modifying those centers. We're modifying our workflows. We're coming up with a different standard operating procedures so that if this is approved/when it's approved, we will be ready on day 1 to instantly turn on the spigot and allow patients to call up and say, I'm interested in this and get them through the process without trying to invent it on the fly. What I will tell you is I had a conversation with our Chief Executive Officer just last week, and he made it absolutely clear that from a Neuronetics Greenbrook Wellness perspective, this is his priority for 2026 is to be ready to handle the volume of patients that have come are going to come to us asking for relief from their depression. And we're up to that challenge. We've been working on it now. We'll continue to work on to it until we get that FDA approval.

Great. Well, thank you for that early work. I know the patients that are waiting very much appreciate that. So I'm going to ask one more question to each of you and maybe just kind of a brief answer off the top of your head, starting with Myriam. What excites you most about the potential of COMP360?

I think similar to you and most people, it's really what it represents for patients and for the field at large. My husband and I build Journey Clinical after personally witnessing the therapeutic potential of psychedelic medicines and with it also feeling a responsibility to create a care model that would deliver them safely, ethically and at scale. And so COMP360 does feel like a pivotal milestone for two reasons. On the -- one, the clinical signal is very compelling with meaningful responses for TRD, and it will help millions of patients where other interventions have plateaued. Two, it will also open the door to new FDA-approved and insurance covered treatments in mental health. Patients deserve real clinical options grounded in evidence to end mental health crisis. And COMP360 is showing that this is possible. So very, very excited.

Thank you. Same question for you, Dimitri. What excites you most about the potential of COMP360?

The ability for this dose to be provided to this massive amount of people. We have 24% of people with major depression that are constantly struggling to have an intervention that works. And this is the new revolution. And for me, what's really exciting is that the revolution around Certified Community Behavioral Health Clinics marrying with this new intervention can access care for so many people that need it. And one of the things, for example, at CCBHC focuses on our veterans. It's a core service of what we do. And as everyone knows, veterans are adopting the use of psychedelics as an intervention. So just think about all of this impact that can occur from COMP360 going across the country with really great clinicians helping people integrate this intervention and really sort of expand the ability for people to live a life that they want. And what's also really great about this, I think, is that there's a bipartisan support for this intervention. There's Republicans and Democrats and the administration supporting this COMP360 intervention. And I think that this revolution is going to be just amazing.

Terrific. And Dr. Grammer will give you the last word.

I appreciate that. Again, I cannot overstate this. Never in the history of medicine has a modality been offered that provides such quick relief and such good durability for our patients struggling with treatment-resistant depression. That does not exist. The comparable model in the medical world, and for those who don't know, I used to do internal medicine before I did psychiatry and is the cardiac cath lab. In the old days, we used to manage angina with tons of meds. It had lots of side effects. People had to stay on them, they remain symptomatic. Now you can go to the cardiac cath lab, revascularize the heart and they're good to go. And psychiatry is changing to that model. We still will have outpatient psychiatrists doing great work, doing therapy, doing medications, like that is part of the plan, just like we have outpatient cardiologists. But we're going to have these interventional psychiatry centers like we have catheterization labs, where we're able to do that instant cath and then sustained relief from symptoms. We are seeing an evolution in the field of behavioral health. And I think COMP360 is what finally pushes this over to the line to broad acceptance within the community and within the medical establishment. This will be a paradigm changer in my opinion.

Well said, well, there's so much more we could talk about. But in the interest of time, I want to thank you all for this lively and informative discussion. And let me now pass the program to Lori Englebert to go through our commercial preparation for COMP360.

Thanks, Steve. Hi, everyone. Thank you for joining us, and a special thank you to Dr. Small and all of our collaboration partners for being here with us today. It is great to see your eagerness to bring innovation to patients and hear your thoughts on how you see COMP360 potentially fitting into your practice. We certainly share your enthusiasm for bringing new medicines to the millions of patients who are lacking meaningful treatment options. We are thrilled to be able to discuss our commercial launch preparations with you today. Having launched more than a dozen products in my career, several of them being first-in-class, similar to Dr. Grammer's comments earlier, the momentum and interest that is building around this exciting new class of psychedelics is unmatched to anything I've ever experienced. Robust clinical evidence in patient populations that have limited treatment options, combined with a transformative new approach to how patients are treated represents a potentially monumental shift for the field of psychiatry. With COMP360 anticipated being first to market and first-in-class, COMPASS is at the forefront of shaping the future of psychiatry patient care. You heard earlier in the webcast about the tremendous unmet need for patients who are living with treatment-resistant depression. Prevalence is high with over 4 million patients in the U.S. alone. And once an MDD patient is considered treatment-resistant being failed by two prior treatments, the burden of disease becomes dramatically higher. Treatment-resistant patients on average, experienced 70% greater work time loss, almost 3x longer depressive episodes and a greater than 50% increased risk of mortality due to suicide compared to MDD patients who are not yet considered treatment-resistant. The unmet need is clear, and we are focused on bringing COMP360 to patients as soon as possible. Given our recent updates on potential time lines, we are now focused on being launch-ready by the end of the year. Preparing for any launch mandates a deep understanding of the landscape and opportunity across various stakeholders, but being first to market in a new class requires an even more comprehensive approach to launch preparation. Over the past 2 years, COMPASS has been very active with pre-commercial work, all with a focus on achieving our goal of ensuring that TRD patients can access COMP360, if approved. Pre-commercial activities have been primarily focused on engaging with, learning from and educating key stakeholders such as clinical care teams across various settings of healthcare delivery through work with our strategic collaborations, KOLs and HCPs through our medical science liaison team, federal and state policymakers through our government affairs team and patient advocacy groups. We are also actively preparing for payer engagement and have already had preliminary introductory discussions with various payers. However, we intend to initiate more robust payer discussions after additional Phase III data, and we can fully characterize the value that COMP360 will bring to patients, providers and the payer system. With the foundational work that we are already doing, I am confident in our ability to accelerate all preparations needed for a successful launch. Today, we are going to highlight three areas that set up the potential of COMP360 in a commercial setting. First, how COMP360 will be differentiated; secondly, how COMP360 is expected to be used in clinical practice. And finally, how COMP360 will fit seamlessly into existing infrastructure. First, regarding how COMP360 will be differentiated. As you heard, there is currently only one marketed medicine, Spravato, approved by the FDA to treat patients with treatment-resistant depression. 6 years post launch, Spravato continues to see double-digit year-over-year increases in patients treated, overall prescriptions, revenue, and new certified treatment centers added, which is an important indicator of future demand. At launch, COMP360 will potentially be differentiated by clinical outcomes and a less burdensome patient experience. As pointed out in other areas of the discussion, our 005 6-week efficacy data is comparable to what was shown in Spravato clinical trials, but durability of effect is vastly different. The rapid and durable results at 6 weeks achieved after only 1 initial administration of COMP360 versus what would require 10 administrations over the same time period for Spravato is highly differentiated and has the potential to revolutionize how clinicians approach patient care. From a patient perspective, you heard Steve mention earlier that 1 day of a treatment center versus 10 over a 6-week period means less days off work, less travel time and less burden on themselves and on their caregivers. In Q1, we will see 006 Part A data at the primary endpoint of 6 weeks, which will be important in helping us understand the potential increased benefit of two initial doses versus one. In Q1, we will also see 26-week Part B data for 005. Although 005 was primarily designed as per FDA guidance to get a safety baseline compared to placebo, we will learn valuable information that could help inform clinical decision-making and start to shape the product profile of COMP360. For 005 Part B, we will see the MADRS curves out to 26 weeks for the important subgroups of remitters, responders, partial responders, and nonresponders. As a reminder, in Part B of both trials, patients who are not in remission at 6 weeks are eligible for another dose of what they were randomized to in Part A or they have the option of going back on an antidepressant. Patients who are in remission at 6 weeks and subsequently relapsed will also be eligible for another dose or to go back on antidepressants at the time of relapse between week 6 and 26. Data over the time course of 26 weeks for these subgroups will help us begin to understand potential frequency of dosing, which will be important to help inform how clinicians treat their patients and also for preliminary payer discussions. We anticipate that prescribing and administration of COMP360 will fit seamlessly within current clinical practice. Based on the expected REMS, we anticipate prescribing of COMP360 will be by a healthcare professional licensed to prescribe medication. And on the day of dosing, we anticipate that monitoring of the patient during the treatment session will be by a licensed healthcare professional. In our clinical trials, monitoring and support was provided by a licensed therapist. But in real-world execution, based on FDA guidance, we anticipate that a patient will self-administer the capsule at the site of care and be monitored for safety over a required time period by a broader trained and licensed healthcare professional workforce. At launch, there are expected to be thousands of available mental healthcare workers trained on how to monitor patients and support a multi-hour psychedelic experience. This workforce includes the hundreds of therapists already trained to support clinical trials as well as the many other HCPs who we expect will be trained through a standardized training program in anticipation of a COMP360 launch. For reimbursement, we expect to make COMP360 available through both specialty pharmacy shipped directly to the site of care and through buy-and-bill. Drug product reimbursement will be billed through the patient's pharmacy benefit. As Steve mentioned earlier, we also anticipate that sites will be able to optimally bill by the hour for the clinical care team's time through a patient's medical benefit plan by using the newly formed CPT codes that were specifically created for psychedelics. At launch, we are prepared to leverage the well-established existing interventional psychiatry infrastructure. These treatment sites are designed and equipped to support products that require multi-hour monitoring, such as Spravato. With over 6,800 sites across the U.S. and growing rapidly, these centers are already equipped with the infrastructure needed and have highly trained staff with the operational know-how needed to support additional multi-hour treatments like COMP360. Importantly, as you heard earlier, many of these sites are already scaling in anticipation of a COMP360 launch. If COMP360 is approved, it will undoubtedly bring a welcomed and meaningful new treatment option to TRD patients and their providers as effective new treatment options are desperately needed. Our launch planning efforts remain focused on ensuring sites are prepared to administer COMP360 and that TRD patients can access COMP360 upon approval. COMP360 has the potential to fundamentally change the way that patients living with depression are cared for, and COMPASS is committing to help as many patients as possible. We understand the market. We understand the potential, and we understand what we need to do to be successful. The launch of COMP360 is poised to be one of the most highly anticipated launches in recent history, and I am looking forward to discussing our launch preparations and our commercial readiness with you over the coming year. I will now turn it back over to Kabir to close this out.

Thanks so much, Lori. And as you heard, we really are getting on with our commercial preparation to be ready to meet the enthusiasm, the excitement and that day 1 demand you heard about from our collaborators earlier. So with numerous important value drivers in place, 2026 is positioned to be a landmark year for TRD patients and for COMPASS. In the back part of this quarter, we expect to report pivotal efficacy and safety data from Part A of the 006 trial with its two fixed doses, alongside more details from Part A of the 005 trial. From that, as you know, we already reported that we met the 6-week primary endpoint last June. And it's going to be important to see the impact of two doses in the 006 trial at the same time as seeing those details from the single-dose trial. Given that we've already met the primary endpoint of 005, seeing a statistically significant result from the 6-week primary endpoint of 006 will more fully derisk regulatory and confirm the compelling clinical and commercial profile of COMP360. For the 005 data from week 6 to 26 weeks, while the primary purpose is to more fully characterize safety, as Lori already described in detail, we're hoping to see on average how long patient responses from Part A last and what the curve looks like with an additional dose in Part B. This will help to inform early payer discussions as well as potential clinical practice. The remaining 26-week data from Part B of 006 is expected in early Q3 of this year, and that will help to inform dosing for labeling and is anticipated to be the last gating item to complete our NDA submission. The entire COMPASS team is focused on disciplined execution, completing our Phase III trials, preparing for our NDA submission and continuing our commercial preparations. We continue to add resources to ensure that we're moving our NDA filing activities ahead as quickly as possible. And with significant commercial learnings already incorporated, we're confident that we'll be ready to launch on an accelerated time line. We're encouraged by the continued increase in interventional psychiatry clinic infrastructure over the past few years, driven both by Spravato, but also, as you heard, by the growing excitement around the potential promise for psychedelic treatments such as COMP360 in the future. The learnings we're gaining through our strategic collaborations strengthen our confidence that COMP360, if approved, could be effectively integrated into that growing interventional psychiatry infrastructure and offer a differentiated and compelling treatment option for patients and providers. And just yesterday, we announced our seventh strategic collaboration with Radial Health, a growing clinic network that is set up to optimize leveraging technology and operations expertise to optimize models of care for patients. As leaders in the field of psychedelics, we're confident in the emerging profile of COMP360 and its potential to transform the landscape for those living with TRD for a potentially rapid and durable treatment option. We also look forward to ramping up our late-stage PTSD program, another indication where we see significant potential and significant potential to impact for patients. Once again, our thanks to Dr. Small, to Dr. Grammer, to Myriam Barthes, to Dimitri Cavathas for joining us on today's call. They will all be with us for Q&A as well the full executive team. So with that, I'll now turn the call over to the operator for Q&A.

[Operator Instructions] So our first question comes from Ritu Baral at Cowen.

To relatively concise questions. One for COMPASS as well as the center leaders. I wanted to ask about your expectations for monitoring requirements upon launch readiness and how the CPT codes may play into that? And then my follow-up question was actually also on the PTSD study that was outlined and the mention of the PCL-5, I believe, which was a key secondary endpoint. Will there be any efficacy requirements for the PCL-5? And how does it differ from the CAPS-5 that's been used in the field before?

Thanks, Ritu. So on the first one, I'll ask Steve Levine to take that. And the second, I'll ask Mike to take. So Steve?

Thanks, Kabir. Yes, the new CPT III codes, which are specific for the administration day of the psychedelic treatment are reportable on an hourly basis. Right now, in our clinical trials, the administration day has been 6 to 8 hours long. We do not yet know whether there may be a specific time requirement stated within a REMS. But it likely, whether within the REMS or not would be at least a 6-hour day. But regardless of that day, because the code is reported hour by hour, all of those hours could be accounted for. Additionally, an evaluation and management code for medical monitoring and supervision could be reported on the same day as the new CPT codes.

Thanks, Steve. Mike?

Yes. So I love the question about the PCL-5. So look, PCL-5 and CAPS-5, and again, I'm going to ask Guy and Steve to chime in if I miss something here or what our expert clinicians on the panel. They're actually complementary tools, right? The CAPS-5 is a clinician-administered fairly in-depth interview about a range of symptoms on PTSD. The PCL-5 is a self-report. And generally speaking, it's probably faster, it's shorter. And so it has a very different feel to it. Those two of them play complementary roles in the sense that from a clinical perspective as well as a regulatory perspective, you want to have independent verification that the treatment is clinically meaningful. Can the clinician observe and elicit information that the patient -- the symptoms are better. But importantly, if not even more importantly, does the patient himself -- him or herself report to you that they're feeling better. So they are complementary tools. The PCL-5 and the CAPS-5 have both been used in a multitude of PTSD studies. They are well-validated tools. They're part of the DSM criteria for diagnosis of PTSD, but they provide complementary information. The PCL in the study is a key secondary. So we need to hit on the CAPS-5 first and then move to the PCL for control of type 1 error, but we have not powered the study on a specific effect on the PCL. And so if I've missed something to my clinical colleagues, please, please help me here if there's something that I should have added.

Our next question comes from Paul Matteis at Stifel.

I wanted to dig in a little bit more on the upcoming 26-week data. Can you guys just like walk through what you're going to present, what you think a positive outcome is? Do you need a p-value? And then I'd love to hear from the clinicians like how are you interpreting long-term data from an intermittent antidepressant therapy. Understanding that as you follow patients for longer, there's compounds starting SSRIs, dropouts, things like that. Like what do you want to see to be comfortable with like a once quarterly algorithm or something even less free?

Thanks, Paul. So I'll start by just addressing what we are going to see, and then I'll hand it to Guy to talk a little bit more about interpretation. So again, clearly, from a regulatory perspective, let's focus on that to begin with, the 6-week primary endpoint is what counts. So we are not looking for a significance of difference between MADRS and placebo arms at any data point beyond the 6 weeks. What we will be showing though is when you see the responses from the patients in Part A segmented at 6 weeks, we will see what then happens to those patients in those cohorts over week 6 to 26. So those who were in remission, those who were responders, and those who are not recognizing that some of those will be getting a second dose in Part B because that was a matter of choice. And that's why we say that will be highly informative around the clinical profile and what actually happens to patients after a single dose and potentially a second dose. But the purpose, again, is not to compare because the placebo arm is going to be somewhat confounded at that point. And again, from a regulatory perspective and what we need to provide from an endpoint perspective, the primary endpoint is what counts. With that, let me pass to Guy to talk -- to address the second part of your question a little around interpretation.

Yes. Thanks, Kabir. Thanks, Paul. I think it's worth bearing in mind that at the moment, we know very little about our primary endpoint in 005. We just know the difference between the two arms. So we'll be very useful to have an effect to know the change from baseline in that trial alongside the trial 006, which represents the effect of two treatments. So I think that will be -- although it's always a little -- it's a little uncertain to compare two different trials. Nevertheless, recruitment criteria are pretty identical, and we should be able to compare, at least broadly speaking, the effects of 1 versus 2 doses at 6 to 9 weeks. So that in itself is going to be an important part of the interpretation. We don't yet know what we're going to see, but that's going to be extremely interesting. I think in terms of the 26-week follow-up, we really don't know what we're going to see. We don't have any really -- real cues around that. We know that patients are getting -- a certain number of these patients are getting retreated. We don't know which group is mainly getting retreated. It could be the placebo group potentially. It could actually be the active group because the active group may be more willing to come for a second treatment because they've been unblinded. We don't want -- we don't argue that 005 is a fully blinded study. We will also, of course, be getting safety, which we think is a very key part of what we get from 005. So in terms of what we want to see there, it would be great to have the safety signal that has been told. We're told we have pretty good record so far from the DSMB. We want to see that confirmed at 26 weeks. And then we want to see exactly what happens when patients get retreated. And we want to see that as an overall effect because, obviously, this is one of the ways patients probably will get treated in real life. They'll get one treatment and then there will be a second one if they need it. And then in addition, we will have a look at whether there's a clear difference between the two arms. As Kabir has indicated, comparison of the two arms in 005 is not a straightforward thing to do because of the fact that over the course of follow-up, the patients who were in the placebo arm may get a whole range of other treatments. And so our intention to treat model, which when you take all comers will increasingly get confounded by additional treatments. There may be a limited per protocol set that we can look at. So all of this is a little technical, but I think what would be -- what good would look like would be to see sustained effects in the groups that Kabir has described and also evidence that a second treatment has a benefit for patients in 005, and to be able to compare that with patients who get a planned double treatment in 006.

Our next question comes from Gavin Clark-Gartner at Evercore.

Thanks for putting on this really informative event. So I wanted to touch on the delivery landscape. And this is a question for the experts, and Dr. Grammer touched a little on this, but I wanted to expand a bit. So Steve Levine had mentioned how COMP360 would be similar or actually maybe slightly more favorable for practice economics and operations compared to Spravato. I'm curious if you've run some of those margin and operational analysis on your own and what you found. And I just had a follow-up.

Thanks, Gavin. So Dr. Grammer, if I may, I will pass that to you.

Well, I think until we get some final figures from payers on what the reimbursement is going to be, there will still be some uncertainty within the modeling of that. But I would say it's not a zero-sum game, right? So there's sort of two benefits. One is you have patient choice, and I'm a big fan of patient choice where people come in and the bigger armamentarium of things you can offer, the better it is for patient care. But the reality is we also just want to bring people into this ecosystem of interventional psychiatry. The reality is only about 15% of people who could benefit from TMS have ever even been offered it, and it's even less with Spravato, I think it's like less than 5%. So we have to actually change the way that patients even think about care. And what we may find are there are some patients where they have a foundation of care that starts with like COMP360 that we layer on top of that between treatments, additional things like TMS and Spravato. So this is not one has to cannibalize the other. I actually think it's a win-win for patients as we leverage these multiple tools to get them into what we hope to be an eventual remission. From -- Steve kind of alluded to this before, though, I think the payer structure is at least going to have to be comparable to Spravato for a room or square footage per hour basis, and it sounds like the general dialogue is headed in that direction.

All right. Great. And on that topic, more broadly, do you envision the psychedelic class supporting the growth of psych clinics? Like you mentioned the cath lab example. What about like community oncology as another example?

Yes. No, absolutely. I mean this is where psychiatry has been going. And I think we're going to continue to partner with the outpatient general providers, psychiatrists, nurse practitioners, therapists and so forth. But we're seeing in psychiatry, this subspecialty form of interventional modalities. And they do require specific training and logistical infrastructure that for the solo practice is nearly impossible to do. But again, not mutually exclusive, it actually works in concert and partnership. I think we're going to see more and more of this idea of interventional psychiatry. I think that's actually the direction the field is going in general, like we've seen with ambulatory endoscopy clinics, ambulatory surgery. I mean, this is just the way medicine is where we're trying to make these things feasible and viable for patients who need them without the burden that would normally come with, say, hospitalization or what have you.

I'd like to just add that the Certified Community Behavioral Health Clinics have a very unique prospective payment structure that's going to allow the ability for our clinics to create a cost structure to do these interventions every day. And there's such a belief in this across the country that the Ballmer Foundation has actually invested $72 million to expand Certified Community Behavioral Health Clinics in Illinois, Michigan, and Kansas. So I'd highly encourage people to look into this new movement in the clinics because the structure is going to be a really wonderful way to facilitate this amazing intervention.

Our next question comes from Leo Timashev at RBC Capital.

I just want to follow up a little bit on Gavin's questions actually. I guess setting aside sort of the general expansion, I guess I'm curious how in each of your clinics and existing centers, you think about scaling. I guess, are you looking initially to just fill out any slack you may have in your current occupancy rates? When you think about the initial scale, is that converting a single room? Or will you be adding rooms, adding facilities? And I guess, how much of the scaling is dependent just on COMP360 success or on success of the class as a whole of the psychedelic class?

Thanks, Leo. So maybe I can ask Dimitri to go first on this one, followed by Dr. Grammer. And I don't know if Dr. Small, you want to comment on that from a Hackensack perspective. But Dimitri, perhaps we can start with you.

We've already have space for Spravato with two rooms right now. We have space already dedicated for the future of COMP360. And we also have a new building that's getting built. And again, for the CCBHCs in particular, there's an ability to sort of create a payment structure to allow for new buildings to be built. So the ability for these clinics, in particular, have a real unique gift to be able to say, we believe that we're going to have these many sessions per week. This is the space we need to do it in, and this is the cost structure. And then that is a conversation with each state to pay for that. And again, what's really wonderful is that there's bipartisan support for CCBHCs, there's bipartisan support for the use of COMP360 and psychedelics, both sides plus the administration. So I'm very confident. I feel very optimistic that this will be able to be a very major intervention in this system of care.

Dr. Grammer?

Yes. So the question is where do we surge this and do we have existing capacity. So currently, at Greenbrook Wellness Centers, we have 170 providers. We have 95 clinics. Most of those clinics have 4 or more chairs and the average is going to be 6. Where I work in Rockville, we currently have 9, and we're expanding to 12, and we run those concurrently, okay? What we do first is we will fill the chairs per hour. When that reaches capacity, we expand the number of hours those chairs operate. And when that reaches capacity, we build out additional brick-and-mortar infrastructure to deploy more chairs. What I will say is one of the benefits of commercialization of this is if the demand exceeds our current capacity, we build additional capacity. But do we have the ability now to fold in something like COMP360 into our Spravato footprint? Yes, we do. And if we exceed that capacity, we'll build out more capacity if we need to.

Okay. Dr. Small, perhaps?

So Hackensack Meridian Health is the largest, most integrated health system in New Jersey. We're across the state from -- we have three regions, Southern, middle region and the Northern region. We're going to start in our Spravato clinics, our eventual clinics and look at that experience and then expand out depending on the demand. So we're very excited about this. This is the health system. I mean, I'm in the California, I was so excited to come here because of the capacity to really help people across the entire state.

Amazing. You traded the weather for this opportunity. And maybe, Myriam, if I could ask, I mean, clearly, scale is somewhat different in your case, but perhaps I could just ask you to comment on that and how you're thinking about scale as well.

Yes. I think, the model at Journey Clinical is built for scale. That means that we're not limited actually by a small number of clinics, we have 3,000 therapists with 3,000 practices. That means if you're a patient, you can literally go to your local therapist office and have this treatment accessible, and we already cover -- we already have insurance. So that means scale will -- is already happening and is going to be easy.

Wonderful. Thank you Leo for the question.

Our next question comes from Judah Frommer at Morgan Stanley.

A lot of great information today. I just wanted to follow up on a comment that Dr. Grammer made about demand for COMP360. Maybe could the panel further characterize where the demand is coming from? Are these patients that have potentially tried Spravato and/or TMS or another treatment and failed? Are these patients that would be newer to TRD treatment? Just curious how you're thinking about potentially sequencing COMP360 if it's approved and how that might affect whether patients are lost to follow-up if there are failures from other treatments?

Okay. Maybe Dr. Grammer, I'll ask you to lead and then go to Dr. Small and we -- everyone can jump in.

The good news is for people who we've seen before that failed to get adequate relief from the modalities we have, we have -- we actually do periodic touch-ins with those folks. We also at Neuronetics, have a patient liaison team that goes out to referring network providers to educate them on the services we offer to facilitate referrals and so forth. And so any launch would be associated with that initiative. We have an entire marketing department to increase that awareness where we do both DTC and referral-based marketing efforts to try to increase that awareness. All those things will be turned on if there's a COMP360 approval. As far as who's interested, it's actually fascinating because there are some people that have relief but not remission from symptoms that want more. And we certainly have those, right? We have those that didn't get better. And that makes a lot of common sense. If you didn't get all the relief you want, you're like what else is out there. But I'll tell you, and this is the thing that has me so enthusiastic about this. I have patients that are in full remission on Spravato that are asking me about psilocybin. I have patients that had a full remission with TMS that are asking about psilocybin. When I said there's this romantic enthusiasm for this particular compound, people are drawn to it even if from a clinical perspective on validated rating scales, they're getting adequate relief from those existing modalities. And there are different reasons for that. So I think you're going to see an interest that is incredibly broad-based, not only from those who haven't gotten better, but those that are but just want something different.

Next, Dr. Small?

So we use a similar strategy at Hackensack Meridian Health, direct-to-consumer marketing. We have a very active group of primary care physicians, and we also have collaborative care where we embed mental health practitioners in the primary care settings. In addition, we have a very active clinical pathways group where we get input from experienced clinicians across the state. And so we try to have a systematic approach to treatment-resistant depression. If somebody fails one treatment, where we go next. So I think I'm very confident that we'll start low and go slow, but we'll build this out and scale it up, so it will have a real impact.

Thank you very much. And I know we've still got a few more questions. So thank you all for your patience as we stay on here through the end of this webinar. So thanks, Judah. If we could turn to the next question, please.

Our next question comes from Jay Olson at Oppenheimer.

Maybe just to focus on PTSD. Can you talk about some of the more recalcitrant symptoms of PTSD and how COMP360 may address those? And then if you could also talk about the in-clinic experience for PTSD patients on COMP360 with regards to psychotherapy, especially considering the emotional challenges of addressing acute underlying trauma.

Thanks for the question, Guy. Let me turn that to you, please.

Yes. Thanks very much for the question. It's a very good one. Our experience is based not just on rating scales. We showed the effect on the CAPS-5 and we also saw a faster effect on the PCL-5. But we did in-depth interviewing with the patients after the trial was finished. And we got some very interesting insights into how the drug appears to work. And one of the things that holds back psychotherapy in this area is exposure to the treatment to the original trauma is often part of the therapy. And it's treated as essentially an exposure experience, which allows patients to desensitize and lose the associated emotionality. What was extremely interesting to us was that although patients came into the study expecting that, that would be kind of what happened for them under the influence of psilocybin, in about half of the patients, it didn't. And yet when they came out of the experience, they found the way they were processing the memory in a different way from the way they had done it when they went in. Other patients did have recall of the experience, but it was often less alarming than they had expected. And the key message to us was that we were preparing them for uncertainty. We were selling them, we don't know what's going to happen, but whatever does happen, you accept it and go with it. And that retrospectively was very good, a very good way to manage the experience. So essentially, what we're saying is that preparation is key. These patients often come in high anxiety. They need reassurance that things are not going to necessarily result in a very frightening revisiting of the experience that may have brought them there, but they will be able to process what happens in a way that leaves them feeling differently about the experience. And I suppose the key thing is that we see a change, particularly in the core symptoms of PTSD. I mean, one of the issue is that PTSD and depression have quite a major overlap. So it's extremely important in this early stage of development of the treatment that we see an effect on the core symptoms of PTSD, the most characteristic, which are the flashbacks. And of course, we would expect to see some effect of depression anyway. But the symptoms that are most troubling, the symptoms that seem to lead to social withdrawal and this sense of emptiness and really withdrawing from life, those are the fear of the return of the symptoms, the apathy. That seems to be something that patients they can reevaluate. They can -- they get into a different frame about it. And it's very striking for people who have seen and interviewed the patients, how there's simply a different look in their eye when they come out of these experiences. So that is the promise. We have to confirm it at scale, and we will obviously be very excited in how this eventually gets implemented in the kind of services you've described. But of course, these patients will fit perfectly into services that are developed for TRD, and there will be a good deal of overlap, actually, a lot of comorbidity in the patient groups who will seek treatment in this way.

Thank you, Guy. And Jay, just to clarify one thing I wasn't sure on your question. We are not offering psychotherapy. So our COMP360 protocol includes monitoring, but it does not include psychotherapy. And perhaps I can refer back to Myriam because I think she made that articulation very clearly around there is a therapeutic container for the patients, but the actual psilocybin session itself does not. So maybe, Myriam, I can pass back to you on that.

Absolutely. And this is what we have been doing at Journey Clinical for now over 4 years. The dosing session itself does not include therapy. The patient is self-directing the experience and what can be added to the real world when COMP360 will be approved is psychotherapy before and after the dosing sessions. And that is the difference that we at Journey Clinical have designed within our care delivery model.

Our next question comes from Patrick Trucchio at H.C. Wainwright.

My first question is on the TRD program. With the understanding that COMP005 Part B is designed to inform safety and dosing rather than placebo-adjusted durability. I'm wondering what from a payer discussion perspective, would you want to see in these outputs from the remitter responder curves? What would matter most? And what should we be looking for? And then on the PTSD program, you've designed a trial to potentially support approval with a single study. What could determine whether or not this program can move forward with a single trial or if you may need an additional pivotal study?

Thanks, Patrick. Well, I'll briefly answer the second one. It will depend on the results of the study. So I think that will be the key determinant in terms of that. We'll have to see what we see and whether that's sufficient to support the dialogue with the FDA. And on the first part, let me ask Lori to address that.

Thanks, Patrick. I'll have a fairly brief response as well. 6 weeks is already -- will be meaningfully different for payers already. I think, again, back to what we -- the point we made in the presentation around Spravato is requiring 10 administrations to get to the same equivalent efficacy that we saw with one dose at 6 weeks. When we look at the 006 -- I mean, the 005, 26-week data, what we will see is the remitters, the responders, the nonresponders, partial responders and nonresponders and what those curves look like out to 26 weeks. I want to make sure everyone understands the payers, anything we see beyond 6 weeks is just going to be additional benefit for payers, for clinicians, for patients. But we really need to characterize based on each of those subgroups, what clinicians will need to look at.

Right. That's helpful. If I could also ask a few on the commercial side, more specifically on the commercial side.

Patrick, absolutely. If I may, just very -- apologies, very briefly interrupt. I know Dr. Small has to drop off. I just wanted to thank him, thank him for staying on. Thank you very much, Dr. Small. Apologies, Patrick, I will come back to you.

Thank you.

Thank you.

Sorry, Patrick, back to you.

No problem. So just on -- I think you mentioned that you'd expect a balance between specialty pharmacy and buy-and-bill distribution to evolve over time. I'm wondering if you could talk about the differences between these two? And is there potential advantages of one versus another and how we should think about this relative to Spravato? And then for the KOLs, I was wondering if you could talk about what are the remaining barriers, whether it's operational reimbursement or staffing to scaling COMP360, even with the CPT codes in place? And what, from your perspective, could the company do to help you to accelerate uptake of COMP360 in the first year of launch?

Lori first.

Yes. So from a specialty pharmacy and a buy-and-bill, you think about the benefits, the benefit is really for the provider -- the center and the provider on the buy-and-bill standpoint, if they buy and bill it, they can get some additional benefit in terms of potential profit margin. But likely, centers will not exercise the buy-and-bill option or want the buy-and-bill option if they don't have generated enough demand to get there. And so we do believe that it will be somewhat of a slower ramp to buy-and-bill. What we know from Spravato now is about 35% to 40% of Spravato is buy-and-bill. And if you think about how Spravato is prescribed right now, highly, highly concentrated to a very small group of prescribers, but very high volume, that's likely where you're seeing a lot of that buy-and-bill opportunity go. The benefits to the patient are -- there is no benefit to the patient on either one. It's very seamless.

And Patrick, for the second part of your question, maybe I can go to Dimitri first in terms of what else you would need to see to build scale and capacity.

Yes. I mean for our journey and mission, we are focused on the Medicaid and Medicare population. And unfortunately, especially with PTSD, people who have the most significant PTSD tend to become disabled if we get them. So we have a slew of people that really need this kind of intervention. And so the ability to integrate this is not going to be a really difficult journey for us. We also have a really wonderful partnership with a specialty pharmacy, multistate specialty pharmacy that already is a large dealer of Spravato and will be able to help us facilitate the use of COMP360 in these clinics such as ours in CCBHC. So I think that the ability of the market for Medicaid and Medicare in particular, is really strong because people tend to become disabled from most significant PTSD. So it's something that there's a lot of focus on commercial insurance, which we take also and all CCBHCs do as well. There's also a lot of focus on obviously buying directly. But the Medicaid and Medicare market, in particular, I think, is going to be quite significant.

Thank you. Dr. Grammer?

Yes. So I think it's interesting. The biggest barrier I see is changing the expectations of patients. So if you look at this TRD population, about half of those patients aren't even currently in care. For the half that are, 80% are being cared for in primary care, not by behavioral health providers. And what we have seen with TMS and Spravato is this sort of uncertainty of how to access the system. So as with any launch, I think it's going to be absolutely pivotal to make sure that not only are we doing typical ways of increasing awareness through marketing and so forth, but really, there needs to be earned media organic buzz to get the word out there to patients who have sort of dropped off the treadmill of care to let them know that there is something fundamentally different and bring them back into the system. And then the bigger thing is or an equally important thing is making sure that aperture for entry into care is as wide as possible. You can't ask someone who's currently depressed to go through all these hoops to try to get authorization to receive the modality. So we need to build in, and we currently have that at Greenbrook Wellness Centers, but build in that infrastructure. So all they need to do is make a phone call, send a chat, fill out a form, do an e-mail, whatever, send up smoke signals and then we take it from there. So the next step for them is showing up for that treatment.

Our next question comes from Tom Shrader at BTIG.

A wonderful event. It's really been fun to listen to. Really related to Jay's question, patients in PTSD, given the potential issues, are your inclusion criteria likely to be very tight? Are there types of patients you're scared of? And I think the question is relevant to the treatment centers also. When you get a PTSD patient, is it the same as a TRD patient? Or are they kind of inherently more worrisome? And then I have a commercial question.

Yes. So maybe on the IE criteria, Mike, do you just want to address that briefly, please?

Yes. So I love the question. So I don't think there's any PTSD patient that we're afraid of. I think that we have criteria designed to make sure that we're recruiting a more real-world population than some other trials. So for example, in these studies, we're allowing some degree of alcohol and substance abuse because that's a serious concomitant comorbidity with PTSD. Clearly, folks who've had childhood trauma or have had PTSD for an inordinate long period of time who are historically not responsive to any treatments, those patients were sort of excluded from the trial. So the criteria are generally aligned with what other studies have done. We try to liberalize it a little bit to make it a little bit more real world. So other than that, as I said, we ran the study by the FDA, and they have actually no comments or issues with the criteria that we have proposed to them.

Thank you, Mike. And Tom, I'll turn the other part of your question to Dr. Grammer and others. But just a reminder to contextualize is, there are only two very old approved medicines for PTSD. So right now, the kind of interventional psychiatry is not really set up to deal with PTSD. But I don't know, Dr. Grammer, Dimitri, Myriam, anyone who wants to take that, please?

Yes. I would just like to say that health systems have a running list of super utilizers of healthcare, people that are utilizing the ER and other health resources. And there is a significant percentage of those super cost utilizers that have PTSD. So I don't think there's any concern around the gradient of PTSD symptomology. And I think if anything, there's going to be a significant focus on people that have the most issues to get this intervention so that we can help not only the person have a much better life, but also to help drive down healthcare costs. So CCBHCs have really great data around these kind of supports to lower healthcare costs. And we see a COMP360 intervention as a key element in helping people that are using ERs for intervention. And the other thing real quick is that we have integrated primary care and primary care is a great vehicle also to engage people and need care. Primary care still prescribes more psychiatric medications across the country than outpatient mental health clinics. So the strategy of primary care and behavioral healthcare facility is really a key to getting access for people in their care.

And real quick on the treatment landscape. The Spravato numbers, if there are 6,800 centers given the sales, that says the average center is doing about 2 a month. And we had somebody today say they're doing either 400 a day or 400 a week. What's the major sticking point to all these centers that can do it, have done it, but don't do it very much?

I don't know, Steve, perhaps you want to take that one?

Yes, happy to. I think, yes, 6,800 writing at least one prescription for Spravato, but as you said, highly concentrated. Dr. Grammer gave the example that you pointed out of one that's much higher volume than most others. Across the other types of sites, I think there's probably a diversity of reasons because there's diversity in the types of sites of care. Much of that concentration is probably in what we would refer to as interventional psychiatry sites that are specifically focused on delivering treatments like Spravato as well as typically TMS, whereas other sites may be delivering a range of services, including medication management or therapy, other psychiatric services without a specific focus on Spravato. So in those cases, it's not necessarily a difficulty of delivering or implementing Spravato, so much as just not as much of an emphasis on exclusively delivering that as a treatment. Whereas some of the others may represent some of the smaller practices that Dr. Grammer mentioned earlier that at least at this point, do have greater difficulty with delivering a more complex interventional treatment than one with that specific expertise.

So our next question comes from Imogen Mansfield at Cantor Fitzgerald.

Thanks very much for the great session. Many of our experts on the call have talked about kind of patient-centered motivation to find access to COMP360. It will be interesting to hear what you think the barriers are for referral patterns from primary care and from traditional psychiatry and what is preventing those providers from recommending Spravato and TMS right now, given that the rates are so low? And how will that change with COMP360? Is it just awareness? Or does the time factor component also provide a meaningful benefit for those providers to refer these intervention options?

Maybe Dr. Grammer, I'll ask you to start and then go to Myriam and Dimitri on that.

It's a great question. And I think there's slight differences between traditional mental health referrals and primary care. Let's start with primary care. Again, we talked about changing the paradigm of care within behavioral health in one of the medical specialties that's been a little bit more frozen in time than others, right? And so it's taking a while for people to understand that the field has changed. So primary care, I think one of the challenges is they're uncomfortable jumping from their level to what they see as a subspecialty within psychiatry, going -- bypassing general psychiatry. And we're working hard on trying to crack that code through a variety of different mechanisms. But that's a lot of educational awareness to that group of providers to let them know, it's okay. And that we'll send them back better and they can continue to manage as they were, but we serve as a resource for them. I think for primary behavioral health is a little bit more nuanced and complex. Some of it is awareness, but I think some of it, unfortunately, is more primitive. When you're in the thick of it with someone trying to get them better, it's easy to kind of get lost within that battle against the depression. And to finally reach a point where you're saying, "Hey, listen, what I'm doing isn't getting you the relief that you deserve, I need to refer you out." Psychiatry is not used to that sort of method of care. Where I brought up the cardiology model before, most cardiologists, like "oh, yes I'll send you the cath lab. I got a body there we'll do that." I think in psychiatry, people are still getting used to that idea without it feeling like they have somehow let that patient down with their very well-intended efforts. The way to overcome that is to explain to those referring providers, we're not a replacement for them. We're not a competition to them. We are an extension of their practice just like that cardiac cath lab. And so we have to have a relationship with them, which is why we have that entire dedicated staff to go out to these referring providers and establish these relationships. I think we need more of that. And I do think COMP360 is going to continue to push that boundary further down the field to where it needs to be where that's much more fluid than it currently exists.

Thank you. Myriam?

This is such a good question, and we've asked ourselves this question so many times over the years in building Journey Clinical. And the reason why we built it is because we wanted to understand what were the barriers for providers to offer ketamine-assisted psychotherapy to their existing clients. And what we have learned is those people tend to be afraid. They want access to training. They really want access to peers and community and other people who are also offering this treatment. They need help with insurance and navigating those landscapes. And so when we came up with this concept of giving licensed mental health professional everything they need to offer these treatments into their practice, that basically opened the floodgates. And it's simply supporting and empowering them through this journey of adoption. And then what we have learned with COMP360, we've actually ran a survey about asking our 3,000 therapists if they would be interested in delivering this treatment within the Journey Clinical model in their own practice and 90% replied that they would. So we have already signaled and evidence that those people who have been offering this type of treatment are ready to start the second this is approved.

Wonderful. Thank you. Dimitri?

Yes. I echo the sentiments I've just heard, they were wonderful. And just to add, CCBHC's core service is same-day access. So people can walk in, we can engage people immediately and then get them set up pretty quickly. We have about a 3- to 4-day wait from access day to medication. So we're really aggressive about engaging people because we know from a change perspective, when people want to change, you have to get it when they're ready. And the more time you give away from that change moment, the less opportunity for that person to engage in what they need. People don't want to spend all those hours to do Spravato. So that is a real thing. And this 1-day kind of intervention is much more palatable to people than this whole other process you have to do Spravato. So I would just say that on the patient side, the time savings is a big deal. And on the provider side, having this ability to sort of engage people quickly is a real key aspect. And referrals are always a very complicated thing, and there's nothing else I can add to what Myriam and Geoffrey said, they really hit it.

Lori, can you just very briefly address what we're doing already to build our infrastructure and capability to support referrals?

Yes, absolutely. And it is a key component and something we've been thinking about quite a bit. So you heard me mention in the remarks that our medical science liaison team has been out educating on treatment-resistant depression on psychedelics on what we've seen so far in COMP360, our trial designs. A key element of what they're doing is obviously speaking to the psychiatry infrastructure that's already out there that could potentially be referrals into these interventional centers. But we are also expanding to the PCPs because the PCP, they already have the bulk of patients who are sitting there who are already treatment-resistant. So just some education around that is starting to happen.

So our final question comes from Sumant Kulkarni at Canaccord.

For this informative event and all the work you're putting in on behalf of patients. I have one set of -- one question for the experts and a couple for the company. For the experts, perhaps starting with Dr. Grammer, in a future scenario where COMP360 is approved and if there is another psychedelic product or 2 that are also approved for TRD, but only require patients to be in your clinics for 2 hours or less, what would be the key variables you'd consider that would make you use COMP360 over those other products?

I think that was to me. So that's a good question. I don't know that I have a good answer for you yet because we don't know the differentiators between the different molecules that may come farther down the pipeline, right? Historically, in biology, durability can be somewhat questionable with very brief interventions to things. So one of the first things that we're going to be looking at is whether or not you get the same durability with a shorter-acting compound that could be offered. The other thing is going to be subtypes of depression or other conditions that may respond to one versus the other. Until we have that data, we don't know. But I think from a commercialized standpoint, the pool of people with treatment-resistant depression is so large. It's not like it's a finite market population. It's almost infinite is one way to think about it. So if there's a molecule that comes along that works equally as well, has the same durability, but a shorter duration of action, it's not like the business drops off. It's that we are able to continue to attend to those patients with the modality we receive. The reality is for right now, the first one up on the list is going to be COMP360. We're prepped for that. We're going to do that. We need to get that right. And as new molecules come on board, we'll kind of adjust and adapt as needed based upon what that data shows. But it's a little premature to really know how we would differentiate those out.

For the company, what would you consider a good result in terms of a major score change for Part A of COMP006 for the 25 mg versus the 1 mg? And could you put that in context versus the 3.6 point adjusted change you saw in Part A of COMP005? And given there's a commercial plans update component to this webcast, what are your latest thoughts on pricing COMP360 for TRD?

Thanks, Sumant. So the answer is statistical significance is the barrier we're looking for. in terms of the MADRS difference in 006 Part A. And I'll turn to Lori for -- it's premature to talk about pricing specifically, but I'll turn to Lori to talk about that.

Yes. You said it, Kabir. It's a little bit premature because it's hard to characterize the clinical profile of COMP360 without our 26-week data or even our 52-week data. So once we have that full picture of what COMP360 and the value that COMP360 can bring to the payer system as well as patients and providers, it's a little premature to think about pricing.

So this concludes today's Q&A session. I'll turn it back to Kabir for some quick closing remarks.

Thank you very much, indeed. And first, thank you all for staying on. I know considerable length beyond the end of the planned time. Particular thanks to our guests, to Dr. Small, Dr. Grammer, to Dimitri Cavathas, and to Myriam Barthes for their really great contributions to the discussion and the Q&A. I think the key takeaway from today is you've heard very clearly that providers and patients are ready. They are incredibly excited about the potential for COMP360 as a new treatment option. They recognize the work that COMPASS has put in to driving this program. They're excited as we are with the data that we're going to see. And what you can take away is that we at COMPASS are truly ready for this transformational paradigm shift in the treatment of serious mental illness through interventional psychiatry infrastructure. So again, thank you all so much for staying on. Thank you for the contributions. Thank you for your questions. And we will look forward to updating you not only with data in the back part of this quarter, but also, as Lori said earlier, as our commercial plans continue to evolve. So thank you very much, everyone. Thank you for your attention, and thank you for your time, and I wish you an excellent rest of the day.