All right, let's get started. Well, welcome again to Day 2 of the Piper Sandler Healthcare Conference. This is David Amsellem from the Piper Sandler Biopharma Research Team. We have Mind Medicine with us, and it's a pretty exciting time for Mind Medicine. So let's get right into the story. We have Rob Barrow, CEO, and Dan Karlin, Chief Medical Officer. So thanks, gentlemen, for joining us. And before we dive into MM-120, I wanted to ask you a question about just the path that you've chosen for the asset. It's very different compared to what J&J did with Spravato, what Compass Pathways is doing with COMP360, given the focus on TRD. You're focusing on MDD and GAD. So can you talk about your thought process in running clinical programs for your product in MDD and GAD versus a narrower path in TRD? Yeah, no, it's a great question. Something we've been really intentional about from the inception of the company and development program is to think really expansively about the potential of the class. And when we have a new class of drug in psychiatry, it's been a long time since we've had a new one. But when we do, there's so many patients in such a great need that it really leads, most of the time, to some really impactful change and practice changes. And in order to facilitate that, having the broadest possible label so that if we get the drug approved for these indications, we can go out into the world and be able to market to and ultimately treat patients with two of the largest and most burdensome psychiatric disorders cumulatively that exist. And so everything we've done has been intended to maximize the opportunity for MM-120 and for the impact this program and really the class of drugs can have for these patients. There certainly were decisions, and I can't speak for other organizations necessarily, but decisions that led to folks focusing on TRD. We've seen other companies and programs who started in TRD and then pivoted away from it, given the challenges and the complexities with it. And one of the rationales, again, is if one studies the broad market indications, a subset of the MDD population is covered by the whole population. So there's nothing that restricts the ability for an MDD or a GAD label to treat the subset of those patients. It just gives us the maximum opportunity as an organization, both obviously economically, but as importantly for helping the most patients. So what can we infer from this broader focus in terms of overall growth and receptivity to psychedelics on the part of practitioners and patients? I mean, you think about, I think about where Spravato was several years ago, and now it's a $2 billion product, or going to be north of that. So it sounds to me like there's just kind of a critical mass of acceptance of neuroplastic agents. Is that what you're seeing out there in terms of patients and practitioners? Yeah, I mean, I can certainly speak to the provider community. And I think maybe the most telling thing in my direct experience of providers, and we've obviously done structured quantitative research, but I teach residents. I end up in a residency program sitting with 20 or 30 people who are training to be psychiatrists. I go around the room and ask, "What do you want to do? What are you training to be?" Because psychiatry can look like a lot of different things. And more than ever, the answers include provide some form of psychotherapy, which is an interesting change. And a massive number of these people say, "I want to be involved in psychedelics." So there are people in psychiatry picking a career path because of the availability of this treatment. And on the other side, so those are the folks, the trainees on the other side of the equation, we've got the chairs of most major departments who are huge boosters of the category and are involved in the research and are writing, suggesting that these can change psychiatry. When you've got the newest and the oldest of the psychiatrists all pushing for safe and equitable access to these drugs when they come to market, it's in really good shape. And on the patient side, it's an interesting thing because how often would you even have the thought, "How do patients feel about a psychiatric treatment?" That has never been a concern or a question in the past. Patients tend to be responsive to provider preference. But in this case, we've got mass media coverage of the fact that progressing a drug that appears to be highly effective and safe and doesn't carry the adverse effect burden that the currently available treatments do that have kept people out of treatment, kept people from seeking treatment, certainly made treatment adherence terrible. So there is this patient interest we never expected development otherwise. So before we delve into the body of data, I wanted to get just a little bit of a refresher on the underlying formulation here and your intellectual property on MM-120. That would be helpful. Yeah, so in MM-120, it's a form of LSD. It's a D-tartrate salt we've developed into an orally disintegrating tablet, partnered with Catalent in commercial exclusivity. We've filed a number of, been granted a number of patents, both in formulation. It has some really important properties and solves for physicochemical stability. It has enhanced pharmacokinetics and pharmacodynamics in the clinic. And so all of those elements have given us a really nice market protection stance where we sit today with issued patents. And obviously, we continue to file a number of applications now and into the future as we continue to progress the development program. We feel really good about some of the discoveries we've had, some of the innovations we've been able to contribute to the field and the product, and the patents have been able to get issued accordingly. Okay, so let's dive into the clinical data here. So let's talk about generalized anxiety disorder. And just help us contextualize the results you saw on your phase II-B in GAD, and I guess how that stacks up against benzodiazepines and reuptake inhibitors. Yeah, and there's a few ways to tackle this, and I'll turn it over to Dan, but we saw the largest absolute magnitude and placebo-adjusted magnitude of change that has ever been seen in anxiety. It's an area where many drugs have tried and failed. The last approval was Cymbalta in 2007. 20 years without anything new for, by the most recent estimates, what is a 10% prevalence in the U.S. Not all these people are treated, and obviously not all of them are diagnosed, but we're still talking about treated, diagnosed, and failed current class being in the mid-single-digit millions of patients here in the U.S. Extraordinarily high need with nothing new, and to have a drug that comes in and beats everything by the widest margin we've ever seen, it got us incredibly excited. I think it surpassed our expectations and placed in every way we slice the data and sets us up for really confident readouts as we go into the pivotal studies. Continue to have that AE burden, it doesn't go away over time, and the efficacy doesn't get better. So benzodiazepines carry their own set of challenges, and the challenges for benzos seem to grow every time you read a new paper. They found some new risk of being on chronic benzos. So I mean, we're talking about a disease state for which pharmacotherapies have really failed patients. And what we saw in our phase II couldn't be on the other side. So I'm particularly interested in the rapidity of anxiolytic and antidepressant response in your Phase IIB in GAD patients. You don't see that certainly with reuptake inhibitors, but even benzodiazepines have their limitations. So can you talk to that and what you saw in terms of rapidity of response? Yeah, so we obviously measure the effect in a number of different ways, as Dan mentioned, overall disease burden and severity. We use more momentary assessments like the CGI-S. And that can be measured at any point in time, whereas the primary outcome assessment, the Hamilton Anxiety Scale, is a one-week recall instrument. So we're a little bit limited on how fast we can measure the HAM-A. We saw within 24 hours almost two-category improvement in CGI-S in disease severity. It's worth spending a second on because in most cases, these are patients who have spent years, decades living with severe anxiety. They come into a study, and they wake up the next day going from severe to mild disease. That is, first of all, it just doesn't happen, right? Almost no one wakes up having lived with chronic anxiety at this level of severity, and it's just improved automatically. And so I think it really does speak to the magnitude of the direct drug action. But to see that magnitude of change that fast and then have it be durable for 12 weeks thereafter, and of course, it shows up when we measure the HAM-A one week later, it shows up pretty much every score we looked at as soon as we can look at it. But the rapid and durable effects, those two things together are things that even when we do have rapid-acting drugs, they tend to not last or need chronic treatment with chronic AE burden and chronic liabilities. Here we're seeing single intervention with this long-lasting tail is a dynamic that is incredibly exciting for us. So let's switch gears to safety. And can you talk to duration of perceptual effects here? And also, did you see any cases at all of suicidal ideation in the Phase IIB? I mean, I'll start with the second question. That is an enormous amount of work to detect, partly just because of obligation to be safe if they are feeling, not only collect that through AE collecting, which is unguided, but guided questioning about suicidality. And there was a sort of a low level of baseline passive suicidal ideation. In all cases where there was suicidal ideation at entry, it was less on some assessment. So no, no suicide success. And suicidality is driven by disease, right? Illness. So the ability to get people better is a suicide reducer, not the, so that's just a really key point here. The duration of the transient effects of the drug are another. So of course, when we talk about perceptible effects, people feeling not anxious anymore is something they are perceiving. But the perceptual effects of the drug, they come on in 15 minutes to a half hour. So people kind of start to feel what they're going to feel. They peak over the next hour or so. And then they persist at a sort of a plateau level till hours four to five. And starting at hour five, people start to be at a place where they are in a phase of safety and monitoring. In Phase III, we're monitoring people for a full eight hours regardless of whether they're ready or not. But we are confident in that eight-hour number being an outer boundary. We are developing tools along the way that we're using in the Phase III that are entirely oriented around assessment of readiness, not from a, "Is there anything drug-related happening anymore?" but from a, "Can this be someone who is safe to be outside of a monitored setting back in the world?" In many cases, the parallel here would be anesthesia. You get anesthesia. Those things are far more severe to you than drugs in our category, then you have surgery, presumably, and you're allowed to leave when you're safe to leave, so we're very much trying to use precedent from other areas of medicine to build rational criteria for when people are considered safe to be in an unmonitored setting. So let's switch gears to the design of the Phase III in GAD. And I'm wondering just why you chose the 100 microgram dose in the Phase III. Yes, Phase II, I think uniquely in the field, we decided to do a comprehensive dose characterization, dose response study in Phase II. We looked at four different doses of drug versus placebo. And the primary analysis in that study was to prove that there was a dose response. A benefit of that analysis is it comes away with a recommended dose to take forward based on that response curve. And so what we observed in Phase II is that at the two low doses we tested, 25 and 50 micrograms, we didn't see a clinical response at all, no separation from placebo, where we saw a dramatic, extraordinarily large response at the 100 and 200 microgram doses. But as we increased the dose beyond 100 micrograms, we didn't have any incremental improvement in efficacy while there was an increased AE burden, both in terms of duration on the day of treatment, patients needed to be monitored for longer, but also things like higher GI disturbance, things of this nature. And so balancing the benefit-risk profile, 100 was a clear dose to take forward and was supported by the modeling. And ultimately, what we selected to test in both of our Phase III studies in GAD and in MDD. I'm also interested in the 50-microgram control in the Panorama study. Can you talk to the rationale behind that? Yeah, this is one of these interesting features, right? So the qualitative nature of psychedelics, of LSD, are unique. The term functional unwinding gets used to talk about the reality that if someone takes 100 micrograms of LSD, and we showed this in Phase II, 100% of people who took 100 or 200 micrograms correctly guess their own drug. 90% of people who took 50 micrograms correctly guess their own drug. Everyone knew, regardless of dose, that they were on drug in the Phase II. But what we're trying to do is use complementary designs as FDA has asked for. We use three different study designs across the program: a five-arm study in Phase II, a two-arm study, and a three-arm study in Phase III. The existence of a lower dose that is both perceivable, as we showed, but not clinically active, allows us to tell patients in the informed consent process, just because you feel the effects of drug on the day of dosing, you cannot assume that it's a clinically active dose. Think of it as sort of a decoy in that way. Now, we don't test that dose. The primary analysis in both studies is still only testing 100 micrograms versus placebo. As it turns out, nothing we learn about 50-microgram response will tell us anything about whether 100 micrograms works or not. We've already established beyond a doubt in Phase II that there is a dose response, and that dose response is not caused by functional unwinding. By using multiple study designs, we're able to really enhance the robustness arguments, right? Show that no matter how we test this drug, it continues to perform. That gives, I think, everyone confidence that there's a real drug effect happening that we can be confident in moving it forward. In the open-label extension, walk us through repeat treatments and how those are incorporated into the extension. Yeah, so the extension phase is particularly interesting in a triggered treatment modality, right? We're not automatically treating people because they've reached the extension phase. We treat people when they've reached a level of disease severity that's the threshold between mild and moderate on the HAM-A, the 16. In that condition, people in their original allocation who are not moderate or worse in the extension phase continue on in a blinded, controlled fashion, potentially all the way through the extension. So we've got this really nice ability to look at longer-term durability in a controlled way. For folks who do have moderate or worse illness at any point during the extension phase, they immediately become eligible for an open-label treatment. And the open-label treatment's delivered with exactly the same parameters as the initial treatment, except, of course, they know what they're going to get in this case. That can happen up to four times over that 40-week extension, though we picked four as sort of an outer boundary, not expecting very many people to get four because we didn't want to artificially limit the edge of the data and stack up against some number that we just picked somewhat arbitrarily. So the thought is that this allows us to characterize as close as you can in a controlled study like this what open-label or what a real-world treatment might look like. So just switching gears on antidepressant effects, how best better contextualize the antidepressant effects you saw in the Phase IIB in GAD patients that ultimately gave you the confidence to move into the EMERGE study in MDD? Yeah, so GAD and MDD are both diagnostically and in terms of presentation significantly overlapping. And in terms of scales we use, I always find it sort of interesting, right? Item six on the Hamilton Anxiety Scale is depressed mood. A feature of anxiety is having depressed mood and certainly a high incidence of comorbid anxiety and depression. We don't enroll patients in GAD studies that are in a major depressive episode, but because of the nature of the scales and diagnosis, we're going to intrinsically have patients who have an elevated baseline depression score above zero, certainly. And that's what we saw. We saw mid-20s kind of MADRS scores in the GAD population, even though these folks weren't in depressive episodes. Again, just like in the anxiety symptoms, we saw a similar response pattern, dramatic reduction that was durable out to 12 weeks, immediate as soon as it could be measured after treatment. And that, in addition to some historical suggestion of activity, both from the class at large and from LSD in particular, gives us a lot of confidence to go into the depression indication. And back to where we started, having both of these indications on the label really opens up anyone coming in with neurotic illness, with either of these indications, becomes a potential patient that we can help, that we can ultimately treat. And so it set us up to progress in parallel to the GAD program and MDD program, where there's also a number of operational efficiencies. When we have sites that are enrolling both GAD and MDD studies, if a patient comes into the GAD study and they happen to be in a depressive episode, instead of losing them, they were able to offer them another option and move them over to the depression program, and that's led to a lot of efficiencies in conducting our phase III studies, and we think sets us up incredibly well for what will be three readouts across those two programs next year. So, jumping ahead, commercialization. I want to spend a little bit of time on that in the couple of minutes we have left. So, how are you thinking about initial targeting? So, will it be the 6,000 or so Spravato centers? I call them Spravato centers there, but they're going to use more than Spravato over time. But is it those centers, or are you thinking more expansively about the target audience because you are going to have a more expansive label? Yeah, it's a great question, and certainly, there's some things that can be leveraged from the Spravato story and the infrastructure that's built out. I think there can be a tendency to over-index on that, and in so doing, missing the future opportunity because they're sort of limited by what exists, and in some ways, that happened with Spravato's initial launch, right? This infrastructure didn't exist, and so it was aimed at a launch in an environment that did exist at the time and was sort of self-limiting until the infrastructure adapted. The way we approach that is to both look at what we can leverage, logistical, administrative dynamics. I mean, these centers that exist that have been certified under the Spravato REMS know how to navigate REMS, know how to navigate controlled substances and prior authorizations, and they have the patients. There's a lot of overlap between MDD, TRD, and GAD. There's an obvious opportunity there. There's also the reality that there's a hyper-concentration of these Spravato centers. A huge percentage of the volume is done in a very small number of centers. The kind of dynamics that need to be in place for Spravato to be most profitable are going to be sort of focused on those high-throughput, high-volume Spravato centers. The rest of that infrastructure, though, is something that we think could be even more appropriate for adoption of MM-120. And so when you look out in the world, we know where these people are, who they are, what the centers are, and they're the ones that tell us, like 80% or 90% say, "When your drug's approved, we want to deliver this." That makes for a pretty easy target to go out and sort of the low-hanging fruit. Undoubtedly, there is more to it than that, and there's a much more expansive opportunity. And again, we don't limit ourselves by what exists today, but rather where we think we can get to with the ultimate opportunity. And so we think about both, starting more focused and then really aggressively expanding that over time. Do you have a good read on what your initial sales force headcount's going to look like? I mean, it's obviously not going to be like a Caplyta sales force or anything like that, but how are you thinking about it? Yeah, it's premature to say precise numbers, but we have a great handle on it. We know exactly what we want to do there and how we're going to go about it. And I think there's sort of a balancing act in that given the manageable size of the audience of the centers we were just talking about as a starting point, it's something that we can easily build and do. At the same time, one of the things that has really allowed us to excel in the development, and it's going to be something we're going to replicate when we think about commercial setting, is being able to really manage relationships with these investigators or providers in the real world, research centers or treatment centers in the real world. And to do that with a sort of white-glove approach where we go in and we make sure that these centers are set up well, that they can support patients well, and that we are supporting them to adopt this, we're not going to under-invest in our launch. That's the only way to guarantee it isn't successful. And so it is something that's going to be hyper-focused and really efficient, but also comprehensive in how we're doing this to make sure that adoption goes incredibly well and is done really safely and responsibly. I want to sneak in a quick question. I know we're out of time, but I want to sneak in a quick question about payer access. So you get a wide label in GAD, right? And that's a vast audience. How do you see payers, I guess, narrowing the funnel, if they do at all? I mean, we hope payers aren't a burden to patients having access to drugs, but it is a reality of our system, and so any opportunities we have to both work with them and to find other avenues to ensure patients have access is something we're going to try to pursue. Those are discussions we've already started engaging in, and we'll continue to progress as we move forward, but given the enormity of the need, there are more than enough patients, even through the most onerous requirements that payers could put in place, but we do think the best interest of patients is the broadest possible access, and it's something we're going to be pushing on very hard over time. All right, terrific. Wish we had more time, but we don't. So I'll leave it there. Thanks, Rob. Thanks, Dan. Thanks, everyone in the audience. Thanks so much.