Welcome to the 6th Annual H.C. Wainwright Neuroperspectives Conference. My name is Patrick Trujillo. I'm a senior healthcare analyst at H.C. Wainwright. We have a robust agenda at the conference this year with more than 30 companies presenting, with their sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats with world-class KOLs on June 16th for the in-person portion of the conference. With a broad CNS drug development focus across multiple indications, from depression and epilepsy to Alzheimer's disease and ALS, and featuring novel methods of drug delivery to the CNS, this is by far our strongest agenda ever. It is my pleasure to introduce our next presenter, Rob Barrow, CEO of MindMed. MindMed is a clinical stage neuropsychiatry company focused on transforming mental health treatment through next-generation compounds, including psychedelics. Its lead candidate, MM 120, a proprietary oral dissolving tablet formulation of LSD, is currently being evaluated in three active 3 trials across general anxiety disorder and major depressive disorder. All the readouts are expected in 2026. Maybe we'll start with MM 120, just the phase 3 program strategy and execution. Perhaps you can begin with a high-level overview of MM 120 and your vision for its role in reshaping the GAD and MDD treatment landscape. First, thanks so much for having us, Patrick. Yes, MM 120, as you mentioned, is in three phase 3 studies, two in GAD and one in MDD at the moment, and currently enrolling. Just building off of phase 2 data we put out last year in 2024, where we showed about half of patients after a single dose were in remission for 12 weeks. This high magnitude and durable clinical effect that we saw, that really has shaped our thinking not only about our phase 3 program, but about how this could potentially fit into the treatment landscape. We've lived in a world in neurotic illness and psychiatry for the last 30 years of symptom suppression, largely relegated to primary care with SRIs. This field and this product have emerged as something that represents a really big leap forward, something that is, we think, going to be transformational. The concept of a single administration that has a multi-month durable effect and is also very rapid in terms of the initial effects is something that certainly, as we talk to psychiatrists and patients and everyone in the field, is incredibly excited about that kind of potential. As we think about the prospect in a phase 3 program, but also in a post-approval world, the concept of a rapid and durable single-dose drug that has that kind of activity is really attractive to us and something that we think has broad appeal in both of these indications. All right, terrific. All three phase 3 trials, the Voyage, Panorama, and Emerge programs are now enrolling. What learnings from the phase 2 trial were most influential in shaping the pivotal program? Certainly the dose selection, landing on a 100 microgram dose, we did a comprehensive dose response study and supported taking the 100 microgram dose forward. That was a critical decision, and some data has been incredibly valuable in shaping our thinking. In terms of the execution and the trial design, obviously, we worked with a number of sites, around 20 sites and 200 patients in the phase 2 study. Of course, operational learnings for all of us, including at the site level, we were able to streamline some aspects of the study and, I think, improve the efficiency with how we conduct these studies. Everything from operational efficiencies on through to aspects of the study design were informative from our phase 2 trial. I will say that by and large, we put a lot of thought and a lot of engagement with regulators into our approach to the phase 2 program and really designed it with the phase 3 in mind. While we have gained some efficiencies and some enhancements, by and large, it is almost an identical study in GAD and a very similar study with only a change in the population and endpoint in MDD compared to what we did in phase 2. Can you talk about the decision to include a 50 microgram dose in Panorama and why it wasn't included in Voyage and Emerge? Hello everyone and welcome to the 6th Annual H.C. Wainwright Neuroperspectives Conference. My name is Patrick Trujillo. I'm a senior healthcare analyst at H.C. Wainwright. We have a robust agenda at the conference this year with more than 30 companies presenting, with their sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats with world-class KOLs on June 16th for the in-person portion of the conference. With a broad CNS drug development focus across multiple indications from depression and epilepsy to Alzheimer's disease and ALS, and featuring novel methods of drug delivery to the CNS, this is by far our strongest agenda ever. With that, it's my pleasure to introduce our next presenter, Rob Barrow, CEO of MindMed. MindMed is a clinical stage neuropsychiatry company focused on transforming mental health treatment through next-generation compounds, including psychedelics. Its lead candidate, MM 120, a proprietary oral dissolving tablet formulation of LSD, is currently being evaluated in three active phase 3 trials across generalized anxiety disorder and major depressive disorder. All the readouts are expected in 2020. Maybe we'll start with MM 120, just the phase 3 program strategy and execution. Perhaps you can begin with a high-level overview of MM 120 and your vision for its role in reshaping the GAD and MDD treatment landscape. First, thanks so much for having us, Patrick. Yes, MM 120, as you mentioned, is in three phase 3 studies, two in GAD and one in MDD at the moment and currently enrolling. Just building off of phase 2 data we put out last year in 2024, where we showed about half of patients after a single dose were in remission for 12 weeks. This high magnitude and durable clinical effect that we saw, that really has shaped our thinking not only about our phase 3 program, but about how this could potentially fit into the treatment landscape. We've lived in a world in neurotic illness and psychiatry for the last 30 years of symptom suppression, largely relegated to primary care with SRIs. This field and this product have emerged as something that represents a really big leap forward, something that is, we think, going to be transformational. The concept of a single administration that has a multi-month durable effect and is also very rapid in terms of the initial effects is something that certainly, as we talk to psychiatrists and patients and everyone in the field, is incredibly excited about that kind of potential. As we think about the prospect in a phase 3 program, but also in a post-approval world, the concept of a rapid and durable single-dose drug that has that kind of activity is really attractive to us and something that we think has broad appeal in both of these indications. All right, terrific. All three phase 3 trials, the Voyage, Panorama, and Emerge programs are now enrolling. What learnings from the phase 2 trial were most influential in shaping the pivotal program? Certainly the dose selection, landing on a 100 microgram dose, we did a comprehensive dose response study and supported taking the 100 microgram dose forward. That was a critical decision, and some data has been incredibly valuable in shaping our thinking. In terms of the execution and the trial design, obviously, we worked with a number of sites, around 20 sites and 200 patients in the phase 2 study. Of course, operational learnings for all of us, including at the site level, we were able to streamline some aspects of the study and, I think, improve the efficiency with how we conduct these studies. Everything from operational efficiencies on through to aspects of the study design were informative from our phase 2 trial. I will say that by and large, we put a lot of thought and a lot of engagement with regulators into our approach to the phase 2 program and really designed it with the phase 3 in mind. While we have gained so3me efficiencies and some enhancements, by and large, it is almost an identical study in GAD and a very similar study with only a change in the population and endpoint in MDD compared to what we did in phase 2. Can you talk about the decision to include a 50 microgram dose in Panorama and why it wasn't included in Voyage and Emerge? Yeah, so the 50 microgram dose, and this is not all that normal of a feature for trials where we have demonstrated a dose, but this is in part a function of this topic that's come up quite a bit in our field about functional unblinding, the concept that patients who take a dose of MM-120 can clearly perceive the acute effects of the drug. A 100 microgram dose of LSD very clearly feels like something. Again, while this is very common in psychiatry generally, we always point to other GAD drugs like Xanax. Milligrams of Xanax very clearly are perceivable. We know this in so many different realms in psychiatry that this is a common feature. Given the qualitative aspects and the sort of significant dynamics of the functional activity of this drug and this field of drugs, the FDA has asked us to include a secondary control effectively. They asked us to do that in one study in the GAD program, and that's why we included it in only one. In both of these studies, our comparison for statistical inferential tests is 100 micrograms versus placebo. The point of including a lower dose or an intermediate dose control is simply so that if a patient on the day of dosing feels the effect of something of the drug, they won't know whether it's due to what we've shown in phase 2 was not clinically effective, a 50 microgram dose, or whether it was due to a also perceivable full 100 microgram dose. Therefore, they can't make any sort of certainty or extension that because I feel something, I'm going to feel better. At least that's conceptually why we include it. Given that it's sort of one aspect of study design and something that is only included in one study, really what it's there for is arguments about robustness. We're trying to show that in three different studies with three different study designs with three different allocation ratios, if we're able to consistently show a strong and durable clinical effect, that will really make a strong case that the drug effect is real and that we can stand behind the safety and effectiveness of the product, hopefully. Right, great. How does the adaptive sample size re-estimation work? How does it help maintain statistical power in the face of potential dropout or variance risk? Yeah, so in both Panorama and Voyage, when we get halfway through enrollment, we do a blinded sample size re-estimation. We make assumptions at the outset of the study. We have 90% power to detect a five-point difference, assuming a 15% dropout rate and a 10-unit standard deviation of our primary outcome measure. Those latter two assumptions, the dropout rate and the standard deviation variance, are what are called nuisance parameters. Again, we make an assumption about them, but if those numbers are different than the numbers we assumed, they do not speak to the efficacy of the drug or how much it separates from placebo. They just create variability. By doing a sample size re-estimation, it allows us to maintain that 90% power even if those nuisance parameters are larger than we anticipated by compensating for that with an increased sample size. What it ultimately does is allow us to be quite efficient with how we think about designing the studies, keeping it on a reasonably sized starting point, but making sure that we do not miss the mark in terms of how we intended to power the study if there is a surprise on one of these random variables that could influence the statistics. Right. How is patient and investigator enthusiasm compared between GAD and MDD? Are you seeing strong overlap among high-performing sites? Absolutely. Strong enthusiasm across the board. We're really encouraged not only in the conduct of these studies, but as we think about the future beyond that, given the really strong enthusiasm that we've seen in both programs. We intentionally wanted to have the MDD study up at the same sites that we're conducting our GAD program for operational efficiencies. These are very, very similar study designs. In GAD studies, we don't include patients who are in a major depressive episode. For patients that come in, and these are highly comorbid conditions, patients who come in who have a GAD diagnosis but happen to be in a major depressive episode, instead of losing them and having to walk away, we're able to say, "Okay, you aren't eligible for the GAD study, but you may be eligible for our MDD study." That way, we get better patient capture, better efficiency in terms of enrollment at these sites. We've designed it that way out of the theory that that would work. We're really seeing that play out now and have been, again, really encouraged by the enthusiasm and how that's translating into the conduct of these studies. Right, great. Maybe just some on efficacy, durability, and dosing. MM 120 produced placebo-adjusted 7.7 point HAM-A reduction in week 12 in phase 2b with effects observed as early as stage two. How are you thinking about replicating that early signal in phase 3? Yeah, we're really excited by that magnitude of change. I think even on an absolute basis, we had almost 22-point improvement from baseline in that 100 microgram group, which was at 7.7 points is a large improvement over an already large placebo response we saw in the phase 2. Obviously, different study designs, different allocation ratios, some features of the phase 3 study that we think very well could result in a lower placebo response in the pivotal program. We're certainly really encouraged by the magnitude of this response we've both seen on a placebo-adjusted and a standalone basis and are doing everything possible, of course, to get high-quality data from this phase 3 program. We'd love to see, I think, anywhere even close to that magnitude of response in phase 3 would be incredibly exciting and positive, especially given that effect is more than double the standard of care in terms of what we've seen from approved drugs in GAD. Right. What measures are in place to assess and define durability across the 40-week open label extension in each study? What will success look like? Yeah, so durability is a really important concept here, right? These are treatments where we expect to have many months' durability as characterized by the week 12 primary endpoint in the phase 3 studies. Because of the nature of our study design, patients in most open label extension studies of a daily drug, for instance, at the time a patient enrolls in the open label extension, they start taking open label drug and therefore are effectively no longer randomized and no longer blinded. A feature of our study is that even beyond part A, the 12-week randomized control period, a patient who does not qualify for open label retreatment, so who would have a HAM-A of less than 16, they are not unblinded. They continue on in a blinded status until they take open label drug. We can look at durability in a few different ways. First of all, 12 weeks after a single treatment is more durability than we've seen with any approved product to date. We can look even beyond that for up to a year. Some patients may well take a single dose in a randomized status, not need another dose for the remainder of the year of the study. In that case, we have a year of durability in a randomized controlled fashion. We can look at that on a single dose basis up to a year. We can also look at durability on an open label basis. Once patients take open label drug, we're going to be looking at the number of treatments, the interval between treatment, what happens upon retreatment, all the features that could be informative to how we think about real-world use of the product if it should be approved. Right. And you've emphasized that MM 120 is a standalone therapy without adjunctive psychotherapy. How do you see that influencing clinical adoption and scalability? One of the critical components in terms of a development program is to isolate a variable, right? We wanted to study MM 120 as a standalone therapy, not because we think that additional psychotherapy or additional psychosocial support is anything but good. We hope that all patients have access to the best possible care. What we need to demonstrate is that the drug has an effect as a drug. That is not restrictive in any way. Really, what it does is it opens up the possibility that clinicians in clinical practice can utilize this as a tool in their toolkit. They can use it as a standalone therapy. They can use it for patients who may already be in psychotherapy or who newly are starting psychotherapy. It's a whole wide range of possibilities in terms of what real-world patient care would look like. We, as a sponsor, as a manufacturer and FDA, we do not dictate how physicians conduct medical practice. We try to develop drugs to establish the safety and effectiveness. Isolating that variable, doing very clean studies that answer that question, we think are really important from a scientific integrity standpoint, but also really important from a regulatory standpoint. Right. And so just moving on to some regulatory strategy and functional unblinding questions. MM 120 received breakthrough therapy designation for GAD. How has that shaped your engagement with the FDA throughout the design and execution of the phase 3 program? We've been really fortunate with the breakthrough therapy designation. It is a program that allows for really constructive engagement with FDA. We try to capitalize on that opportunity at every opportunity, every chance we get. We have continued to have a strong, frequent dialogue with the division, with the agency, really working together and partnering on how to expedite development of this program and try to make sure that we are as efficient as possible with the overall program. We have a tremendous amount of respect for FDA and the engagement we've had with them to date. Under the breakthrough program, that's only expanded and accelerated how we're thinking about approaching the regulatory process. Can you walk us through the primary endpoints across Voyage, Panorama, and Emerge and how they align with historical regulatory approvals in GAD and MDD? Yes, so in Voyage and Panorama, obviously in Panorama, there's three arms, but in both studies, the primary endpoint is the change from baseline to week 12 in the Hamilton anxiety scale between the 100 microgram dose and placebo. In Emerge, it's very, very similar, which is the change between 100 micrograms and placebo. But in that study, because it's depression, we're looking at the MADRS as the outcome measure and at a six-week primary endpoint, which is consistent with a long history of FDA guidance and regulatory approvals. The Hamilton anxiety scale in GAD is the regulatory endpoint that has been used to approve all of the products that are currently on the market for GAD. It is a well-established gold standard in GAD clinical trials. A 12-week endpoint is really longer than many approved products. There are approved products that are approved based on only around four weeks of clinical activity or clinical efficacy. Again, to show the kind of durability that we were able to in phase 2, if we're able to replicate that in the phase 3 program, we're using the standard endpoints at standard time points and are hopefully going to be able to demonstrate really rapid and durable clinical effect for months after a single treatment. We've already talked a little bit about functional unblinding. How do you anticipate the FDA will evaluate functional unblinding? We've talked about the use of the 50 microgram dose arm, but I'm wondering also about how blinded central raters help also mitigate that risk. Yeah, so the blinded central raters, of course, the potential biases in clinical trials can come in many different forms and many different places. Because of the nature of the functional effects of MM 120, we try to separate the adjudication of the outcome measure from anyone who is on site and could be unblinded functionally. We did this in the phase 2 program. We're doing it again in the phase 3. We use blinded centralized raters who are blind not only to treatment assignment, but also visit numbers. They don't know if it's a patient's first visit in the study before they've received drug or if it's 12 weeks after a high dose of MM 120. That gives us additional confidence. What we showed in phase 2 is that while patients were clearly functionally unblinded, they could clearly tell at any dose that they were receiving a dose of drug. The central raters in that study were not. They stayed blinded and were not able to guess with any degree of accuracy. Most just said they were uncertain whether a patient had received a drug or a placebo. It gives us additional integrity in the study design, additional controls against potential functional unblinding in the program. We have had a great dialogue with FDA across the board, including with respect to functional unblinding. We have aligned around the primary endpoints in our study being the 100 microgram versus placebo. That 50 microgram dose there as a control arm is there as a sort of methodological control. A fundamental reality about statistics and logic is that you can't learn anything about group C or group A by looking at group B. So a 50 microgram group just doesn't tell us anything about what's happening with placebo or the drug that we're trying, the dose of drug we're trying to get approved. And so it's there as a control, but it really doesn't influence our primary assessments of efficacy in any way. Right. Maybe a few now on commercialization and market differentiation. First, just how are you thinking about payer engagement, step therapy requirements, and whether additional health economics or real-world evidence will be necessary for market access? Yeah, we've already had really constructive dialogue with payers and will continue that as we progress through the development program. Like with most new products, there typically are prior authorization requirements and tends not to be a first-line therapy right out of the gates at least. We certainly are making plans for whatever those engagements may hold and wherever we may end up. We have an incredible health economics research team and they're continuing to generate that evidence even today and put out publications and posters in that regard. GAD has been sort of a dormant overlooked condition for a long time, in large part because the drugs that were being developed do not work particularly well against GAD symptoms. Trying to make sure everyone fully appreciates the magnitude of the problem and the disease burden and all of the challenges that are associated with for patients who live with GAD is something that's really important to us. We're going to continue to build that body of evidence as we progress closer and closer, hopefully to approval. What infrastructure is needed to support MM 120 administration? How do you plan to leverage the interventional psychiatry model to ease adoption? Yeah, it's a great question. I think there's been probably an overestimation from observers of the field in terms of the kind of infrastructure and even the kind of infrastructure investment that would be required. Based on the data we've generated to date, we're not seeing physiological risks emerge. We certainly anticipate that patients are going to need to be in an observed clinical setting by a healthcare practitioner. The kind of infrastructure that has already adapted to uptake other interventional psych treatments, including things like TMS, Spravato, Ketamine, these locations could very well be appropriate locations, as could many others. While the interventional psychiatry model that exists and has grown pretty rapidly over the last several years is a great starting point, we think the opportunity based on the dynamics of our product and the way it could be delivered could open up even more opportunities that are broader than that. We are certainly engaged with many types of providers, including interventional psychiatry providers and networks that have shown a huge degree of engagement and a definite desire for new products like MM 120. Engaging strongly and they are going to continue to as we progress. Right. Great. Just moving on into MM-402. You recently completed a phase 1 single-setting dose study for MM-402. What were the key learnings in terms of tolerability, pharmacokinetics, and pharmacodynamics? What are the next development steps for MM-402? Should we expect a phase 2 efficacy trial in autism spectrum disorder to start in 2026? We had phase 1 study was quite informative. Obviously, in phase 1 studies, we're looking to find a dose and show that it was well tolerated enough to be progressed forward. We got great definition of the PK and PD in that study, and it has informed how we think about dose selection and where we go next with that program. The next steps, obviously, we want to progress at some point into a study of patients. We haven't given exact timelines around that, but have continued progress with that program. While right now with the pivotal programs ongoing in GAD and MDD for 120, I think a lot of attention has been paid to that program externally. We're certainly progressing not only 402, but also looking at other earlier opportunities in our pipeline for potential progression. We're really excited about that program. As we progress and get closer to being able to offer clarity, we'll be able to share a lot more about what comes next in terms of study design and timing. With a cash runway that runs to 2027 and the amended agreement with K2 Health Ventures, how are you thinking about capital flexibility and optionality heading into the key data events, particularly in 2026? We've been really fortunate to have strong support from not only equity investors and raised a little over $250 million last year in equity offerings. K2 has been great partners with us in allowing us to have that flexibility, have that optionality, and to make sure that we're in the best possible financial position as we're progressing and as if we're getting closer and closer to pivotal data to maximize that optionality and be in the best possible position for every outcome is exactly where we want to be as a company. We feel very fortunate again to be in such a strong position today and are going to continue that in that position of strength, hopefully for very long into the future. Finally, what do you think investors are missing about the MindMed story? Certainly we see an incredibly expansive opportunity, even if we're just talking about MM 120, our late-stage program, our programs in GAD and MDD. When we go out and engage payers, we engage patients, we engage providers, we certainly believe all of the ingredients are there for a really transformational kind of product that changes essentially even ways in standards of care and ways GAD and MDD are cared for. I think the magnitude, certainly this is something new, right? This is something that is not following the standard SSRI model that has been the dominant model of the last 30 or so years. As with anything new, I think there can often be a missing of the scale of the opportunity and a misunderstanding about some of the complexities. There's undoubtedly a lot of work to be done, but we think that work is very achievable and should hopefully position us for a really impactful product that changes the lives of many, many patients. I think the scale of what we can achieve is something that we are incredibly optimistic about. I think everyone over time, if we're able to generate the kind of data we have and have the kind of success that we hope to have, everyone will come to fully appreciate just how impactful this product hopefully can be. Right. Terrific. It is a very exciting time for MindMed, and we truly appreciate your time today, Rob. Thank you to the MindMed team for attending the conference. Thank you to everyone for attending our conference. Have a great rest of your day and a great rest of your conference. Thanks much.