All right, thanks very much. It's my pleasure to be introducing MindMed here. Rob is going to give an overview of the company, and then we will do some Q&A. Take it away. Thanks very much.
Yeah, thanks everyone for being here. I guess, high level, who we are as an organization, I think I'll probably just not read the slides and just give you a bit of an overview of what we see. We've had a lot of progress over the last few years. We're a company that's developing psychedelics, two programs in the clinic with two phase 3 programs and three pivotal readouts next year. First program, LSD D-tartrate, MM-120 we call it, which we're developing in generalized anxiety disorder and major depressive disorder. Coming off of some really exciting data last year in 2024, where we demonstrated a really strong dose response and efficacy about double the magnitude of the standard of care every way we look at it. Then durable efficacy out to 12 weeks after a single treatment.
For those who aren't familiar with what we do with these molecules, we bring patients into our clinic, give them the drug, keep them there for effectively a workday, and at the end of the day, they go home. By the next morning, we can detect really dramatic improvements in a variety of symptoms and overall disease severity in these psychiatric disorders that, again, are persistent out to at least 12 weeks after that single treatment. We subsequently launched the two phase 3 programs, have three studies enrolling right now, two GAD studies, the first of which will read out in the first half of next year, the second of which will be in the second half of next year, Panorama. Then our first study in major depressive disorder.
In phase 2, we also observed an effect on depressive symptoms, and so kicked off a pivotal program there, and we'll have our first pivotal readout in depression in mid-2026. I really need to convince people that anxiety and depression are high impact or large disorders. These are some of the most burdensome and largest disorders in all of medicine, but especially in psychiatry. There's nothing bigger than these two indications. It just cannot speak enough about the desire and really the need and the demand from practitioners to have something new. We've been working in GAD. The last approval was Cymbalta in 2007, after its initial approval in 2004. Twenty years with nothing new. Over that time, the prevalence of GAD has tripled.
We have 10% of U.S. adults who, when we conduct epidemiological studies, show symptoms of generalized anxiety disorder, even though only a portion of those are actually diagnosed. When we have the ingredients of a huge population, a huge burden of disease, and a field that is really demanding this kind of innovation, it gets us incredibly excited about the opportunity that's ahead of us. Mechanistically, it's always a question for any psychiatric drugs, what is happening to drive these effects. Here, it's especially interesting because the clinical effects persist and last so much longer than the actual drug exposure. We're not used to acute interventions with long-lasting clinical effects, but it's exactly what we've been observing in our research to date. Largely driven by serotonin 2A receptor, it's obviously a system that's been largely implicated in psychiatry for a long time.
Those acute effects, though, drive a degree of neuroplasticity and changes in the brain that we believe are correlated with these longer-lasting changes in patient experience and clinical outcomes. Getting into phase 3 data, we observed a dose response study, really the most comprehensive and only true dose response study that's been conducted in this field. Some really important findings there at a top level, rapid, as I mentioned, durable, and high impact effects. We had about half of patients, 48%, who were in clinical remission 12 weeks after a single treatment. The magnitude of the efficacy was such that the effects, almost no matter how you look at it, were more than double the standard of care. Benzodiazepines and SRIs are predominantly used in GAD today. Over time, we saw these dramatic changes, again, detectable as early as they can be measured.
The HAMA is a one-week recall instrument. When we looked at the effects one week after treatment, we saw already a near maximal effect that was maintained with no loss of activity through the subsequent 11 weeks out to week 12 in the study. The same is true for depression symptoms. GAD, MDD, anxiety and depression symptoms are highly overlapping, both in terms of construct and in terms of presentation. The fact that we observed this dramatic reduction in depressive symptoms in GAD population also gave us a lot of conviction to go on that second program and launch a pivotal study in depression. From a safety standpoint, really not a whole lot to speak of, a really favorable tolerability profile. Patients were largely, the effects were largely limited to the day of dosing.
Acute transient perceptual alterations that are mechanistic, that are the effects of taking LSD. However, we go to great lengths to characterize those and document those as adverse events so they could be appropriately labeled if we're successful getting product approved. The other thing we did in the study, and it's a 50 microgram dose as noted here, we did a dose response study. An important feature and an important question that comes up a lot in our field is that of functional unblinding. It's a sort of funny construct where patients who take the drug pretty reliably know that they're getting the drug. That's especially true at high doses, 100 micrograms of LSD, and we showed 100% of patients correctly guessed that they were getting drug.
We interestingly showed them in that study that 90% of patients who got 25 or 50 micrograms also correctly guessed they were getting drug, even though they showed no clinical separation from placebo. It was a really fascinating finding to show that patients know that they're getting drug regardless of dose, but only the high doses work, which both puts to rest any concerns about functional unblinding being the driving effect of clinical activity, but also gives us some really important arguments as we progress with the development program now that we've established that evidence and have it to bolster the robustness arguments about the clinical effects of the drug. Speaking to that, when we look at the landscape for currently approved therapies in GAD, we saw, again, almost 22-point reduction from baseline in the Hamilton Anxiety Scale.
When we look at SRIs and we look at benzodiazepines, we're looking at low teens, 12- 13-point improvements in the HAMA with those drugs. The fact that we saw a 7.7-unit improvement over an abnormally large placebo, both, again, gives us comfort around the robustness of the clinical findings, but also the magnitude of the change that we're able to drive with just a single dose of drug. Going into the pivotal studies, of course, gives us a lot of confidence that we feel good about being able to replicate in all of the phase 3 studies we're running.
Why do you think the placebo effects in these types of interventional studies when you have some unblinding are so big?
Yeah, we really point to three different features that likely drove the placebo response we observed in phase 2. The first is just in studies where there's a higher allocation ratio to any dose of drug, regardless of disease area, regardless of drug, that tends to drive up placebo response.
Right. Did the people on placebo in this study think they got LSD?
About a third of them did.
Okay. Interesting.
Largely probably driven by the fact that we had these lower doses. So 25 micrograms, yeah, the patient's still going into the room if they're getting placebo. They're sitting in a room, they have eye shades, they have music, they have reading writing materials, their phone's taken away.
Sounds like a great day.
Sounds like a great day if you ask me. I mean, we love the Steeple Conference, but a day in a room by yourself sounds quite nice. We saw a third of the patients guess that they were on drug even though they were getting placebo. The other is a bit of a numerical feature of this, which is that in the phase 2 study, we offered patients drug and asked them to come back for the subsequent 12 weeks. They did not get any other benefit from the study. There was no other intervention. They did not have an open label extension like we do in phase 3. As a result, the patients who did the worst were the most likely to leave in the placebo group.
If I have a patient who got treated, they were highly anxious, came up with a high degree of anxiety, washed out of background therapies, they take the drug and they feel worse, they got placebo, we saw them leave at a disproportionately high rate. The problem is their data then is imputed as if they were part of the patients who continued on in the study. That placebo response numerically is going to look inflated compared to.
Your placebo response because of MMRM actually, like if you did LOCF, your data would probably look a lot better.
Presumably, when we looked at this, yeah, the placebo response comes down if you do LOCF.
Right. Makes sense. Okay. Interesting.
All of those features, though, are addressed favorably in terms of placebo responses to go into the phase 3 program, one-to-one or, I guess, three-to-two allocation ratio to get drug in the phase 3 study as opposed to 80% in phase 2. We do have a 12, after the 12-week period, and I'll go here, opportunity for open label treatment. There is now an incentive for patients who are not feeling good to stick around in the study and continue on and get to that open label treatment. All of those features we think give us an even better chance of seeing a reduced and hopefully a more normalized placebo response. When we look at the historical studies, we typically see a 7-9-point placebo reduction, not 14. Most of the active drugs that are approved only get to 14.
If we see that placebo response come down in phase 3 it of course gives us an even wider margin to show a separation between drug and placebo. Across the two indications, two studies are ongoing, as I mentioned, in generalized anxiety disorder. Voyage is our head-to-head study, 100 micrograms versus placebo. Panorama, our second pivotal study in GAD, is testing 100 micrograms versus placebo also. Again, to try to bolster the robustness of trial design, we include a lower allocation, so 50% or 50 patients who get a 50 microgram dose of drug. That is again there so that patients in the informed consent process can be told, just because you feel the effects of drug on dosing day, you cannot assume it is the real thing. We have previously shown 50 micrograms feels like a drug effect. Patients guess they are on drug, but it does not have any clinical effect.
We do not actually care what happens in terms of the clinical outcomes for that group. We, of course, do as human beings, but not in terms of the data from the study. It is there as a secondary control, methodological sort of control, as a sort of decoy to try to confuse expectations and try to maintain the robustness of the clinical outcome assessments. Parallel designs in major depressive disorder, slightly smaller enrollment, 140 in Emerge, 175 in Ascend. Emerge will be reading out, we just moved up the timeline for that, it will be reading out in mid-2026, and Ascend, our second study, will be starting in mid-2026. Really excited to get to these pivotal readouts next year and to be launching a second study in depression along the same timeline. Let's see. There has obviously been some regulatory less.
A year ago, there was an advisory committee for MDMA, and obviously there's some regulatory concerns that were raised. I think as folks have gotten a better understanding of those dynamics, we have had an incredibly constructive dialogue with FDA, but we like to just point out many of the design features. We use centralized raters in our studies who are blind to both the treatment assignment and visit number. Again, we go to great lengths in terms of how we've designed the studies to maintain the integrity of the outcome assessments. We've also, having done really the first and only dose response study in the field, now have that evidence, all that I've been describing, have that evidence in hand to now have it already taken forward to FDA to into phase 2, but to continue to build that evidence base.
At the end of the road, what we hope to be able to do with two successful phase 3 studies is to say to FDA and to the world, we've now tested the drug in three different study designs, three different allocation ratios, and each time we're seeing a robust clinical effect. This is as tall of a bar as you could ask of any drug program.
Do both GAD phase 3s need to work for you to be able to have an approvable product?
Oh, we're going to feel the strongest if we have two. Of course.
Have you gotten any regulatory inclination on the 2B and if it counts?
We designed that study and the primary analysis of the study was a dose response analysis to establish that. While it certainly we believe would be supportive evidence, it was not designed as a pivotal study. We, of course, have seen if we see an incredibly strong effect in one study, we're going to have that conversation. We're always going to be thoughtful. We have had a really constructive dialogue with FDA, but we're banking on two studies in both indications. Given the history of this drug class, we want to stand up to any degree of scrutiny at any point in time. Trying to take shortcuts is never in the long-term interest of a drug program.
I get it. Makes sense.
I've sufficiently spread through a lot of this. I think we can talk a little bit about the commercial landscape. This is an interesting and sort of evolving discussion. We always, again, point to all of the ingredients that are there to make for a massively impactful launch. When we look at any new drug class entry in psychiatry, we are in every instance talking about multi-blockbuster drugs. I mean, benzodiazepines were multi-blockbuster drugs for a long time. Got the introduction of SRIs, we have about a dozen of them, and each of them were blockbuster drugs. When we see the level of interest from providers, the level of need from patients, the kind of value and clinical utility that we have with 120 has all of the makings for a really enormous market opportunity.
Of course, the question that's always asked is, well, how is this actually going to work in the real world? This isn't done this way in practice today. That is a correct statement. It shouldn't be, it can't be because we don't have drugs like this that have been proven to work and that have been approved. We, of course, look to the future and believe that the world needs something new. The world of psychiatry desperately is asking for something new and that this could offer a best-in-class opportunity to drive that uptake. We have seen sort of a stepping stone to that future we think is possible with intranasal esketamine, Johnson & Johnson's SPRAVATO. A lot of that infrastructure is certainly leverageable as we think about the delivery of 120 and this psychedelic class over the coming years.
Again, it's a bit of an apples-to-orange comparison. We're talking about a drug that is incredibly burdensome to deliver with SPRAVATO . When we look at the sort of durability, I mean, the first four weeks of SPRAVATO on the label require twice-a-week administration and then once or every other week thereafter. What we see a lot of times is patients either discontinuing in the vast majority of cases and therefore not getting any more benefit, or patients coming in over and over and over again over the course of the year for up to 56 visits in a year, which is highly impactful. The fact that we're able to drive this high magnitude, long, durable effect that is just flat out different. It is different in every way than what we see with any approved drugs.
We think in almost every instance and positively different has the makings again for a really incredible opportunity ahead of us when we get the drug on the market, hopefully.
On the durability side, why is your durability so much better than pretty much everything else? Is that an LSD thing or is that more about not discrediting the drug, but is this somewhat of an artifact of the population you're treating?
We certainly believe it's an artifact of the activity of the drug.
You don't think like GAD lends itself to better durability in some ways versus like, say, a TRD?
Not necessarily. If anything, depression is an episodic illness by definition. To terminate a depressive episode could in some ways drive longer durability in itself because then patients out of episode, they would need a new episode to emerge in order to sort of lose efficacy. Those new episodes in most cases do not happen. It is on a two-week cycle where this happens. GAD is often, for approved drugs today, often the second or third indication that is pursued because it is so difficult to treat. It is a chronic sort of constitutive illness that in many cases, the sort of time from onset of symptoms to diagnosis is 10 years on average. A lot of patients are living in a highly anxious state, not knowing that life can feel any different.
That sort of chronicity to the background disease, there's an open question. Of course, we'll see as we get to phase 3 data, we'll actually have data to show between anxiety and depression, what is the durability response? What do those retreatment patterns look like? Given the complementary designs we have across those programs, there should be some really interesting insights as we get to those phase 3 data.
Is there any reason to question that retreatment with this wouldn't be efficacious or wouldn't be safe?
Certainly nothing that we've seen so far. I mean, we are intent on characterizing those dynamics. I'll flip back to sort of how we're doing that, of course, is to look at beyond 12 weeks, if symptoms return, so if patients have basically a return of moderate symptoms of anxiety or depression in their respective studies, they can receive an open label dose of drug. What we've seen from evidence out in the real world and compassionate use programs and from some prior academic evidence is that if anything, subsequent treatments drive incremental pickup and sometimes almost asymptotically that it's not necessarily a sort of linear pickup of improvement, but sometimes patients who don't have any response on the first treatment, the second or third dose of drug drives this sort of sudden high magnitude, long-lasting effect.
We're, of course, really interested in characterizing the intervals between retreatment, the nature of those retreatments, but we haven't seen anything to suggest that subsequent treatment would lose efficacy in any sort of way.
Okay. Okay. Makes sense. On MDD, I guess to what degree do you think you're seeing this independent mood effect versus to one degree, could it be like you help the anxiety, which makes people less depressed?
It's a great question. I mean, it's a feature of.
Does that question even matter for the study? Like I guess obviously it depends on the population in your phase 3, but it reminds me of the Kar-XT dynamic with cognition. Benefit cognition, but is it because of psychosis? Again, I don't know if it obviously depends on the trial population, but how do you think about that?
I mean, yeah, the constructs and the measurement tools are so significantly overlapping. There's a diagnostic overlap between GAD and MDD of something like 60%. So 60% with one have the other. Construct-wise and real prevalence-wise, there's probably more like 80+%. Out of an artifact of the evolution, there's a great longer story. I mean, maybe I'll diverge there for a brief second. The vast majority of psychiatry's history has been more focused on anxiety than what we kind of modernly think of as depression. It was the advent and the introduction of SRIs and PHQ-9 that drove diagnostic screening for and increased prevalence of diagnosis for major depressive disorder. Now, that is not to say that one is real and one is not. Both are true.
The diagnoses are so, or the disorders are so significantly overlapping in what they actually are that it is very easy to be diagnosed with GAD and MDD. In GAD studies, we screen out patients who are in a major depressive episode. If you think of the Venn diagram in GAD, we're only looking for GAD or MDD outside of an episode. Someone who has had one major depressive episode.
How do you distinguish that? I mean, your madness is so high.
That is an artifact of the overlapping symptoms, right? I mean, I always point to this. Item six on the Hamilton Anxiety Rating Scale is depressed mood. So a feature of the anxiety scale we use is to measure depression.
Right.
That is sensible because of the degree of overlap. Depression is an episodic illness, right? Patients who have major depressive disorder, having had one episode, then can go a life without ever having a second episode. They still have MDD, but they're not in a major depressive episode. In practice, the way we do it is we use independent, we use site-level structured interviews, the Mini, for instance, to establish a diagnosis. We use a third party to independently verify the diagnosis. We do screen outpatients for item-level criteria, for instance, on the HAMA that are specific to depression that wouldn't be features of anxiety. We don't have cutoffs for overall HAMA score, but for specific items we do. Interestingly, the opposite isn't true. In a depression study, we don't have any regard for whether or not a patient has GAD or not.
Typically the focus has been on trying to isolate these effects in one or the other with more of a sensitivity to trying to screen out depressive episodes in GAD than vice versa. Pragmatically, it does not matter a lot if a patient shows up. This really speaks to our approach for the program. Our goal is to have both on the label at the end of the day. A patient shows up with either anxiety or depression symptoms, anxiety or depression as a diagnosis, and there is a path for them to get MM-120. That is how we tap into this very large, hard-to-treat population.
Right. Right. If we're thinking about even like, let's say you just launched and you just had GAD, if we think about the positioning of 120 versus say like a psilocybin or a DMT or S PHQ-9 , is the funnel still coming down to like it's the same type of patient that is going to be getting a psychedelic?
In many instances, probably.
Kind of you're saying there's like this overlap and like I'm thinking probably at least right now, these are going to be patients that have failed multiple therapies. They're probably pretty severe. It's always one thing I've been wondering about is like to what degree, like I love anxiety is such a huge market, but to what degree is this like a distinct population versus kind of in that same pool that everybody's hoping expands? Does that make sense?
Yeah. I think as we've seen sort of evolve with SRIs, and this could be an easy proxy to look at as how practice works. Certainly, SRIs that are approved only for depression are used off-label to treat anxiety, although less reliably so than the drugs that are approved for anxiety, right? When we think about the sort of patient population again, with a 60+% diagnostic overlap, it's not hard to conceive of the fact that we're going to have patients in every program that's after GAD or MDD are going to have overlapping patients. It is about where a patient is in the progression of the disorder and what the current symptoms are.
Because of the nature of MDD being episodic, being sort of a cyclical illness, the other thing that means is that to treat a major depressive disorder patient, you have to wait for them to have a depressive episode, whereas GAD being a constitutive sort of background disorder that people are living with on a daily basis, that whole population becomes a path to treatment today. A thing that is almost certainly going to be the case early on is that payers are going to want both documentation for past treatments, of course, but also ideally on-label treatment. Getting a drug paid for when it's being used off-label is going to be much more difficult for early adoption. Having both on the label gives us, I think, the easiest and largest market to go after.
Also, with most programs in our field aimed at treatment-resistant depression, even though we again anticipate that payers are going to require some prior failures to pay for the drug, from a marketing standpoint and who we can ultimately go out in the world and say, "This drug may be for you or for your patient," having both of these disorders on the label means a much, much larger population than having a narrow TRD label.
Makes sense. Cool. Should I keep firing away?
Let's go, yeah.
On the commercial side, how should we think about the practice-level economics of something like this versus a SPRAVATO?
Yeah, much higher efficiency to deliver 120, right? When we think about the number, let's just look at sort of the number of hours that would be required to treat a patient and get paid for an eight-hour session, right? It comes down to two sort of dynamics: monitoring time, and I guess we'll go here. It comes down to monitoring time, which is reimbursed typically on an hourly basis. If a practice is set up for buy and bill, they're going to make some margin on the drug. Now, from a unit pricing standpoint, of course, the durability and the magnitude of change dictates how much a dose of drug typically costs. We typically think of annual cost of care.
For a clinic who is going to be treating a patient and making some margin on the drug, if they're losing all the patients because it's so burdensome to treat, then for a given patient, they may make 10% of what the annual cost of that drug may be. If the SPRAVATO was $50,000, let's say, and the patient only shows up for five, and they're making even a 10% margin, which they're not, all of a sudden you're eating substantially into what the actual realized profitability for a site of care is versus if you have a single treatment at a higher cost because it's driving longer effect, there's sort of a higher efficiency of revenue capture for the site. The same is for recession monitoring. For a clinic delivering SPRAVATO , it's a two-hour session.
In order to get paid for monitoring eight hours of a workday, they need to have four patients come in back to back. That is in contrast to a patient who comes in one time, they're there for the day, get reimbursed for a day.
Is there any economic advantage to stacking patients with SPRAVATO , like having three patients all hang out in the same room?
Absolutely. We certainly.
Can we do that with 120?
Of course, it's going to be dictated by what the use practices and label and REMS are, but there's no reason to believe that we couldn't. There's no reason to believe that multiple patients couldn't take the drug. Certainly when we talk to practicing psychiatrists, they say, "Absolutely, this is how this is going to be used." Likely there's going to be a lower degree, someone working at the top of their medical license, not a physician, not a clinician necessarily, but we think of clinical social workers, clinical psychologists who are doing a lot of psychotherapy today are perfectly equipped to monitor someone who's received this drug. Of course, there's going to have to be connectivity to prescribe or for monitoring.
When we think of the dynamics of delivering 120, having three or four patients in a treatment center, getting the drug at the same time where there are a couple of people watching the patients for the day is incredibly attractive to these sites of care. It is highly efficient, and it is pretty low effort to deliver the drug, watch a patient for the day. Even in our clinical trials, a lot of the sites say, "It was a period of time when I did not have to do very much. I sat in the room, watched the patient, but I caught up on notes or I caught up on reading other than the trial assessments that have to be done." Those dynamics we think, and we have tested.
I mean, we go out and talk to sites of care and ask, "Which of these, SPRAVATO or MM-120, would be favorable, more profitable, easier for you to deliver?" The vast majority tell us that they prefer and would be more profitable with 120. Both the sort of theory of it and also the direct feedback from sites of care give us a lot of excitement about the real-world adoption of this.
Makes sense. So a bunch of readouts next year, well capitalized to when?
End of 2028. We just completed financing a couple of weeks ago and brought in $242 million of additional net proceeds. Going into 2026 with three pivotal readouts in a really strong position, we feel really fortunate for where we've been and excited to deliver some hopefully high impact data.
Yeah, that's great. What have you said about filing timelines?
We haven't said yet, but of course, when we look at sort of precedents in the field for approved psychiatry drugs, typically the time to file is somewhere in the 9-12 month range, but we like to hold ourselves to a much higher standard and go much, much, much faster than standard.