Welcome, everyone. Losing my voice here. There we go. Thanks for joining, everyone. I'm Gavin Clark-Gartner, one of the senior biotech analysts here at Evercore ISI. Really happy to be here with Robert Barrow, who is the CEO of MindMed. Thanks for joining us, Rob. Thank you, Gavin. Absolutely. All right, so why don't you just start us off with an overview of the company, where things stand today, and I think it'd also be worthwhile to touch on some of the recent additions to the team. Yeah, absolutely. So, MindMed, a clinical-stage company working on psychedelics and a variety of mental health disorders and psychiatry. Furthest along being our MM-120 program in generalized anxiety disorder and major depressive disorder. MM-120 is a formulation of LSD that we're developing, starting with those two indications, and I think there's certainly potential for others as we go forward in the future. Over the past few years, we've built out the organization to about 75 employees. We just recently added Dr. Javier Muñiz, who was a former associate director of psychiatry at FDA, and also a great regulatory leader who's heading up regulatory and quality assurance, Greg Pratt, who was leading the Cobenfy approval for Karuna Therapeutics until recently, so we've just continued to build out the organization and have a lot of progress over this year. We're embarking on Phase 3 programs for both anxiety and depression now, and three readouts in 2026, which should be an exciting couple of years ahead. Yeah, absolutely. Maybe worthwhile to touch on the landscape overall. So I guess the bigger picture question is, mechanistically, where do you see 120 and LSD fitting into the broader psychedelic space? Yeah, LSD, obviously, there's a number of drugs that are called psychedelics, and that term has been used with some lack of specificity. Generally, we think of the classic psychedelics as serotonin 2A agonists, psilocybin, and DMT being among the other drugs in the class. LSD has been the most studied drug of any of these historically. You can kind of go back in the history of research on the class, and about 10 times more research with LSD than anything else. It's more potent. It's longer acting on a receptor engagement basis. So at almost every level, mechanistically, now what we're seeing clinically is that we're getting better target engagement, and ultimately what we think will translate into best-in-class efficacy and tolerability in the clinic. Yeah, that makes sense. And I'll ask one bigger picture question, then go into 120 and your development program a little more in detail. But with the RFK nomination, do you think that changes anything from your perspective? Certainly, a lot of the discussions we've been having have been very positive. If anything, I think there's a wide recognition, and it's not just the new administration. It's really Congress and executive branch, and it's a bipartisan view that while we certainly have some treatments that some patients benefit from, the trajectory of the mental health epidemic in our country, and really around the world, is really unfortunate. It's going the wrong direction, and we need something new. We've had the drugs and the treatment options we have today have been around for 30 years. And if they were doing their job, if this current system was working, we wouldn't be heading in the direction we are. And so there is a broad recognition of a need for something new, a willingness to think creatively and think boldly about what the future could be. There's a lot of reasons to be optimistic. So we see, both from a new administration, but also just really across the board, an enthusiasm for bringing something that is this different and that could be this big of a game changer forward into the world in the future. Yeah, absolutely. All right, so let's go into a little more detail on the anxiety market. So why don't you just lay out current treatment paradigm where the largest unmet needs are today? And I guess also, as you framed, it's a very large, broad market. So as you start thinking about commercial strategy, are there any patient profiles or segments that you may initially look to target? Certainly, with any new drug, we expect that at some point we'll end up with prior authorizations. That isn't really a significant barrier. We see that with new entrants in depression. I think anxiety has been, and GAD in particular, has been an indication that has been overlooked for decades. I mean, really, with the advent of SRIs, the introduction of Zoloft and Prozac, there was a pretty massive diagnostic drift over from anxiety historically to major depressive disorder. Now, even over the past few years, there's been a really renewed recognition of the role that anxiety plays as a precursor for other severe and significant psychiatric disorders like depression. There's really been almost nothing new in anxiety. The last approval in GAD was Cymbalta, which was 20 years ago. Over that time, the prevalence of GAD has tripled. So yeah, we're talking about 10% of the U.S. adult population that would be potentially treatable. Those are massive numbers. And I think the dynamics of care and anxiety are also really important that when a patient shows up with depression or anxiety symptoms in primary care, they're typically put right on an SRI. By the time they get to a psychiatrist, they almost certainly have failed one or more of the currently available therapies, which are dominated by SRIs. I mean, Xanax, benzos are also available, but they've sort of fallen out of clinical favor and can have a number of liabilities. So where we end up thinking about focusing are patients who have tried multiple treatment options at the outset, certainly. What we see as far as disease burden and health economics is that severity is one of the best predictors of burden in GAD. So patients who have high anxiety scores, who have gone through first-line treatment and then have failed, and then, of course, are most likely in geographic locations where these drugs are likely to be delivered first. There's a pretty massive infrastructure that's evolved to deliver ketamine and esketamine, which is only a starting point. It's a very sort of small starting point. But those locations, it's really dominated by five to 10 states and about 20 metro areas around the country. So both geographically, from a patient population, I think we have a very clear view about the severe patients as a starting point. And then as we progress, we'll certainly broaden out much further. Yeah, that makes sense. It's probably worthwhile to touch on the data on anxiety that you have generated to date, specifically not just the effect size, but I think the durability is very important. So maybe frame that piece and specifically on durability, what you think is kind of the minimum bar to be commercially viable in terms of durability perspective with the mechanism? Yeah, so what we saw in Phase 2, we had a 200-patient study with five different arms. We saw a 7.5-point improvement over placebo, which the effect size, as you mentioned, is more than double what we would expect from the standard of care. We saw that action and anxiolytic effects within 24 hours of the dose in a single dose that had at least 12 weeks of durability. So patients, on average, got better as soon as we could measure it and stayed better through the duration. As we talked to clinicians and KOLs as well, a thing that got everyone especially excited was that we put about half of patients into remission, and that remission was sustained for 12 weeks. So single dose of drug, we stopped following patients after 12 weeks, and there was no reversion back to baseline either. Seeing a multi-month durability after a single treatment is something that we just have never seen before in almost anywhere in psychiatry. In terms of durability, as we go into Phase 3, we're doing a year-long study where we'll observe the durability of a single dose, and then patients will have the opportunity for open-label retreatment after the 12-week period. In terms of minimum viability, I think it's an important dynamic here where it's not necessarily a uniform, a fixed interval where everyone's going to be taking it at every three months or every six months. And so what we've seen from the real world is that for some patients, they need a single dose, and it really puts them into remission, and they stay better somewhat indefinitely. For patients who need a subsequent dose, we see a sort of incremental pickup. And so in many instances, we're seeing patients that would need two or three doses and then are sort of indefinitely better thereafter. So I think we certainly want to understand the care dynamics and the characteristics of retreatment and the durability, but it won't necessarily be uniform, even within a given patient, but certainly a sort of population level. As we go, our primary endpoint in our Phase 3 program is 12 weeks. In monotherapy and severe GAD or MDD, that's about as long as you can reliably keep patients off of any background medicine. We wash everyone out of any background therapy. So there's just a sort of practical limitation on how far we can realistically prove that in a parallel group study. But certainly, as we see durability for three months, that would far exceed the kind of burden equalized in terms of delivery, the burden equalized durability that we see with things like Spravato. And so it would be already an upside. And if we can go out months beyond that, even better. Yeah, that makes sense. And you definitely touched on the Phase 3 trial. Maybe lay out any additional design attributes of that study. I think specifically it's worth spending a little time on how you approached dose selection, since I know there was a lot of thinking that went into that. Yeah, so I mentioned in Phase 2, we did a five-arm study. We looked at a full dose range, really the first dose exploration in the field, looking at doses from 25 micrograms, which is right at the threshold for any sort of perceptual activity, up to 200 micrograms, which ended up being double the clinical dose we're taking forward. We saw an important feature of the conduct of these studies that gets talked about a lot is expectancy bias, functional unblinding. That's why FDA asked us to add in, kind of go above and beyond anything that's been asked of past drugs in anxiety and depression. But we included in one of our Phase 3 studies, and this is in FDA's guidance, we include a second control, a lower dose arm. It's important that that arm has perceptual effects that, as closely as possible, mirror the active drug effects. Ideally, that arm isn't efficacious. It's there as a control. What we showed in our Phase 2 study is that at both 25 and 50 micrograms, patients reliably could tell that they were on drug, but they didn't have any clinical response. We're talking less than a one-point improvement over placebo at 50 micrograms four weeks after the dose. In the Phase 3 program, one of the studies is a head-to-head design where we're testing 100 micrograms versus placebo. The other study we include a lower allocation, 40 patients who receive a 50 microgram dose. The point of that dose is to be able to tell patients as they come into the study, look, if you feel the effects of drug, we're talking about LSD, people reliably can tell that they're on a high dose of LSD. We're able to tell patients, if you feel the effects of the drug, it may be the real clinically active dose of drug, or it may be half of that dose that in previous studies we've shown have no clinical effect. Really, the point is to try to separate the expectancy from biasing the clinical outcomes. Again, there's nothing you can do to take away the fact that people feel the effects of the drug. And so it's an important sort of design element because FDA has asked us for it. But really, it's there as a secondary control. And our statistical testing in the study is going to be our active dose, 100 micrograms versus placebo in both of the studies, regardless of the design. Yeah, that makes a lot of sense. Thinking about the trial on the more operational side, maybe any comments on how you approached site selection as you're broadening out to Phase 3, how you're ensuring really data quality there? And I guess also on the enrollment speed side, within the psychedelic class, Compass has seen some delays in their trial. Maybe any commentary on why you don't believe you will see that dynamic as you move into Phase 3? Yeah, starting with site selection. So many of our best performing sites from Phase 2 are continuing on the Phase 3 program. There's been certainly a really sort of groundswell of enthusiasm for research in the drug class. So mostly where we have focused, entirely where we have focused, are experienced sites who have done trials in anxiety and depression, many of whom in the past had not done trials with our drug class. And over the past few years, since we completed and conducted our Phase 2 study, have built out those capabilities and have the staffing, have the room set up to do these studies. So really, in terms of data quality and integrity, our team is extremely hands-on. We're in these sites. We very much have a close eye on the operationalization of the studies and the data and the quality that we see coming out of the study. In terms of speed of enrollment, so in our Phase 2 study, again, 200-patient study took us 12 months to enroll. We had 20 sites. We have about 50% more sites, but the same number of patients in Phase 3, so 200-patient Phase 3 study and 240 in the second, and our first Phase 3 study, Voyage, we have 30 sites this time, roughly 30 sites, so we certainly expect to be able to keep up the pace of enrollment. I think the barriers to enrolling in these studies come down both to study design and population. It was very intentional that we chose to go after the broad label for GAD and the broad label for MDD. And a lot of the other programs in our space have been focused on treatment-resistant populations. From a marketing standpoint, we think it's better to have an opportunity over the long term to really broaden out, and if we're able to get the drugs on the market, to pick up patients, whether they have failed zero, one, or two, or many treatments over time. From an operationalization of the study standpoint too, we don't have a threshold where patients have to have failed prior treatments ever or immediately in a current episode of depression, for instance. And then we have a very much a fundamental sort of principle that we're going to have clean study designs where patients get a single dose. We're going to prove out the durability, and then we're going to give them the opportunity for open-label treatment. Everything from population down to how we design the studies, down to how we are involved in the recruitment and making sure that the sites hit their marks, we really pride ourselves on the execution. So far, our team has done an incredible job both in Phase 2 and getting the Phase 2 program off the ground. Certainly going to try to keep setting that standard as we go forward. Great. And thinking about the depression study that you're in, maybe just kind of frame what data that you've generated in anxiety de-risks the depression side of things, and specifically as we're thinking about this indication on the safety side as well. Are there any considerations as you move here? Are there higher rates, for example, of suicidal ideation, et cetera, in this population? How do you think about that as you're moving here? Yeah, so the depression indication we've seen historically from investigator-initiated studies and historical literature that there's an antidepressant effect, I think with the class, but with LSD in particular in our Phase 2 study. Anxiety and depression, GAD and MDD are both overlapping in terms of the diagnostic criteria, but also in how they're measured. I mean, there's something like an 80% overlap between the HAM-A and the MADRS, which are the two endpoints for the respective indications. So in Phase 2, we did measure depressive symptoms. We saw patients had slightly lower MADRS. Patients couldn't be in a major depressive episode. But just by the nature of the scales and how they're conducted, they were in the mid-20s on the MADRS for depressive symptoms at baseline, which means that there was some degree of symptomatology that we could pick up and saw a pretty dramatic response, both acute, same sort of dynamics, a rapid and durable response in terms of depressive symptoms, even though patients started at a lower baseline, sort of less room for improvement, so building on all of that evidence, we designed a study with 140 patients, 70 per arm, looking at 100 micrograms versus placebo and MDD. It's at many of the same sites. A lot of the times in our GAD program, we screen out patients because they are in a major depressive episode. There's so much overlap, and then we're able to roll those patients onto our depression study, so we don't lose them entirely. We're just reallocating them to a different study. Certainly, some of the defining features of depression versus GAD, I mean, typically when a patient is presenting with elevated suicidal ideation or suicidal behaviors, it almost immediately pushes them over into an MDD diagnosis, and so there's always the reality of that as part of the condition that we'll be monitoring closely. Regardless of indication, we have really extensive safety protocols in place and regular engagement with those patients at the site, so again, something we monitor, something that we certainly, as we get into bigger populations, and you're talking about serious mental health disorders, you expect there's going to be some degree of suicidal ideation for any drug, regardless of the class or what have you, but nothing that is acutely concerning. I think also going after the broader population probably lessens that concern when you're looking about a treatment-resistant population. Yeah, awesome. And I think we'll probably do a different call to touch on commercial in a good amount of detail since we can't do that in the last minute here. But maybe I'll just end with a regulatory question then, since this has been one area of investor focus this year with the Lykos AdCom interjection. Maybe just kind of frame on a higher level, what were your key takeaways from the AdCom and the process? What were your learnings and what does not apply to what you're doing? Yeah, we were very fortunate to have our End-of-Phase 2 meeting very shortly after the Lykos AdCom this past summer. And there were a lot of, I'd say, themes from that AdCom that allowed us to have a really constructive dialogue with the agency. Virtually none of the bigger problems that emerged that stood in the way of an approval and an AdCom recommendation for approval apply to us. From day one, we've built the organization, our studies, and the conduct of our studies with the highest rigor in terms of how we assess adverse events, how we capture data, the data integrity, making sure that everything is done to the standards that would be expected of any drug. So certainly an unfortunate outcome for that organization and for the patients who could perhaps benefit if it ultimately does get approved. But we don't see a whole lot of relevance in terms of our program and are really confident based on our engagement with FDA very regularly about the prospects for approval in the future. Yeah, that makes sense. Well, very exciting 2024 for Mind Medicine and look forward to an exciting couple of years ahead. Thanks for joining us, Rob. Thanks so much.