Good afternoon, everybody. Welcome to the Jefferies Global Healthcare Conference. My name's Brett Gallagher with the Healthcare Investment Banking Team. It's my pleasure to welcome up Rob Barrow, CEO of MindMed.
Great. Thanks everyone for being here and for Jefferies for hosting us this week. It's an exciting time for us as an organization and our field generally. We're hitting a really interesting point in the regulatory environment and our development programs that gets us really excited about the years to come. Before we start, I'll put out the disclaimer that it will include forward-looking statements, and those are as of today, and obviously they may change, and we will not be changing them here on the stage if they change subsequently. We are working—MindMed is an organization, it's a phase III clinical stage development organization working on the drug class of psychedelics, a class that's been sitting on the shelf for the better part of the last 100 years.
What we've seen so far in modern clinical data is that there's real potential in treating some of the largest and least well-controlled conditions in psychiatry today. We, as an organization, have had a lot of momentum and progress over the last 12 months or 18 months. March of 2024, we put out phase II data, the only and first comprehensive dose-response study in the field. We saw remarkable efficacy results, which we'll get into, and allowed us to get a Breakthrough Therapy designation from FDA and subsequently to have really strong engagement across the board, both here in the U.S. and throughout the world with regulators to map out a path to get these products ultimately to market, hopefully with some successful data from our phase III program. In terms of pipeline, our primary focus in late stage today is on our lead program, MM120.
It is an ODT formulation that we have received patents on and that has some unique advantages both physiochemically but also from a clinical standpoint in terms of its behavior and performance in patients. We have ongoing phase III studies in both generalized anxiety disorder, two studies, and a study that is ongoing in major depressive disorder, all of which will read out next year in 2026. We also have an early stage program with the R-MDMA, which we are developing initially in autism spectrum disorder. This is one where our field has been characterized by a lot of historical assumptions and sort of inherited practices from an era that is long past that we have intentionally not followed. We want to be evidence-based in everything we do. With that second program, the analogy we like to draw is how psychostimulants are used in ADHD, right?
In ADHD, patients take a psychostimulant every day, and it allows them to focus. In autism, where there are no drugs approved to treat the core symptoms, the goal is that the pharmacodynamics of R-MDMA would allow patients who otherwise have a social communication deficit to improve that social communication deficit. Obviously, earlier stage, but if successful, it would be the first program ever to show that kind of effect in that population. When we look at the current landscape, and most of the rest of this will focus on our later stage programs, when we look at the current landscape for GAD and MDD, we have been living in an era for the last 30 years of focus on SSRIs. Our lead indication, the one that we had phase II data on last year, is in generalized anxiety disorder. The last approval was in 2007 with Cymbalta.
We have been living in an era where the only focus is on a framework of fast med management meetings in psychiatry, largely that happens at primary care. We have around a dozen SRIs, but we still have a growing problem with anxiety and depression. Part of the shift away from anxiety was because the drugs we have were not particularly well equipped to treat them. We saw chronic use of benzodiazepines fall out of favor, rightly so, in many ways, due to abuse liability and some of the adverse events that are associated there. What we hear from patients and physicians is just an urgent need for new products that actually drive meaningful change. So much of what we have been doing is symptom suppression. Really, for the first time, we see an opportunity to have a sort of transformational impact on this population.
Some of the patient testimonials, as they come out of trials, suggest that those that are getting better say, "I do not just feel less. I have a new relationship to the disorder that I have been living with in many cases for decades." Incredibly encouraging. Again, talked about the chronic sort of symptom suppression. There is also, I think, an interesting challenge that comes with this. We have millions of patients that would be potentially eligible for treatment. We have a model that everyone has gotten used to, even though it is not good enough, it is underserving the patients we have. The current model that is so low touch and not particularly effective is one that emerged because of the availability of these treatments. Again, it is the model of the SSRI era. Where we want to go is a whole new state, though, and that is going to require changes.
It requires changes in how we think about drug development and clinical trials. It requires a redefining of what good looks like for these patients, and then ultimately a clinical infrastructure and a clinical model that recognizes that and embraces it and leads to that ultimate change. What we've seen in our clinical data, which we'll certainly get into in greater detail, is rapid action, durable responses. About half the patients that got a single dose of our drug in phase II were in remission 12 weeks later. And it's just because we stopped following them at 12 weeks. It's another thing that I think is underappreciated is just how big of a pull there is from psychiatry. Many of us have gotten very well familiar with J&J's intranasal esketamine product, and there's been a pretty substantial infrastructure build-out to adopt that. It's a nice proof point.
It's certainly not the optimized, best-case scenario for what products could do or for what a treatment paradigm looks like for providers. When we go on and ask interventional psychiatry clinics, and we ask psychiatrists generally how they are thinking about psychedelics in anxiety and depression, and we see the numbers here, I mean, the availability will change their approach. 86% of providers that are doing SPRAVATO and ketamine and TMS and ECT today say that's the case. 74% of all psychiatrists, and this is survey data that we generated internally. These are numbers that are practice-changing kind of feedback from the field. This isn't incremental change. This is a whole paradigm shift and something that providers for so long have been asking for and are now really embracing as we get more and more data accumulated.
Digging a little bit more into our lead program, LSD, like the classic serotonergic psychedelics, and it is a pertinent distinction. Even FDA's guidance on psychedelics says that out of convenience, a lot of drugs are lumped together. Ketamine and psilocybin and LSD and MDMA are not part of the same drug class. Psychedelics has basically come to mean drugs that feel like something. There is no surprise that a high dose, 100 microgram dose of LSD very much feels like something, and that's good. That's an okay thing. These drugs work by agonism at serotonin 2A in particular. That drives network effects in the brains. We talk about things like the default mode network. It drives neuroplasticity.
Really, even though the sort of loudest noise in the room, the thing that people focus on are the perceptual alterations in terms of the sensorium, it really drives an also similar sort of change in sort of the cognitive framing of one's self-narrative and the things about anxiety and depression that are driving its recurrence and its duration. This is one I almost never have to spend a whole lot of time on in any discussion because everyone knows that anxiety and depression are highly prevalent disorders that have been growing rapidly. We've had the drugs we have today for 30 years, and yet the rates are still growing. That's why there is the need, and that's why we have such an incredible opportunity.
A thing that also gets missed, and it's worth spending a second on GAD, GAD is a disorder that has been overlooked for so long, so we do not have many drugs available. The burden of GAD is also extraordinary. So much of the focus was intentionally shifted away from anxiety. I mean, most of the history of psychiatry going back to the early drugs, thalidomide was an anxiolytic, right? Barbiturates were anxiolytics, benzodiazepines, and then we get the advent of SRIs, and all of a sudden there is a pretty strong push to move diagnoses towards depression. It turns out SRIs work a bit better on the anhedonic symptoms on the depressed mood and such and can be acutely anxiogenic in treating GAD.
When we look at this framework, we think, of course, there's an incredible opportunity in GAD, but given the prevalence, given the focus on both of these disorders, we have programs in both and aim to be the product on the market that has the broadest possible appeal. That when patients show up with neurotic psychiatric disorder, it includes things, of course, GAD and MDD, but also other areas where we could explore in the future that would become the drug of choice. Our program, our phase III programs, again, two studies ongoing in generalized anxiety disorder, one study ongoing in major depressive disorder with a second study that we anticipate starting at some point in the future. These are largely replicas of what we conducted in phase II. Our phase II study, again, we'll get into in a second.
Voyage, our first phase III in GAD, is a 200-patient study, randomized one-to-one to our clinical dose, 100 micrograms versus placebo, 100 patients in each of those arms. Twelve-week primary endpoint using the Hamilton Anxiety Rating Scale. It is the primary endpoint for every approved drug in generalized anxiety disorder. It is a well-trodden path that we understand very well. Second study, same design, same primary endpoint, same comparison, 100 micrograms versus placebo. Because of the feature of this drug class, that they have such clear, profound perceptual alterations on the day that patients take the dose, FDA has asked all of us, all sponsors in this field, to include a secondary control.
I think the point of that has been, I think, confused at times, but the point effectively is to be able to tell patients, if you feel something on the day of dosing, it may be a real dose of drug, or it could be a dose that isn't clinically active. We showed in phase II that our 100-microgram dose group had an effect that was more than double the standard of care. That is both on an absolute basis and on a placebo-adjusted basis. 50 micrograms showed nothing. It was the same as placebo, statistically, clinically. To be able to include that allows us to add a layer of integrity in terms of the interpretation of the overall program. At the end of the day, if these two studies are successful, we'll have three studies, three different designs.
The point of showing continued clinical activity across those three studies is that we can make robustness arguments. No matter how we study the drug, if it keeps performing and keeps outperforming placebo at a large magnitude, that gives us really strong evidence that there's something real happening here that isn't just people saying, "Oh, I feel something that I'm going to say I'm better." I mentioned it before, the rapid effects, we can't measure the Hamilton Anxiety Rating Scale before one week after dosing. The one-week recall instrument is how the instrument is set up. We can use momentary assessments like the CGIS, Clinical Global Impression of Severity, that is used across medicine. There we see reductions as early as the next day and statistically significant two-point reductions within 24 hours. Those reductions then translate into one-week Hamilton Anxiety reduction and a 12-week durable response.
Again, 48% of the participants in our phase II study were in remission, meaning a Hamilton Anxiety score of seven or less 12 weeks after treatment. These patients came in with severe anxiety with a starting point of around 30, which is quite severe. When we look at the historical drug classes, benzodiazepines, SRIs, effect sizes, so normalized for the variance in those studies, around 0.36, 0.38. We saw an effect size at 12 weeks of 0.81. Regardless of how we slice the data, we're seeing more than double the standard of care on almost every point. Another feature, the adverse event profile is very limited to the dosing day. It mostly looks like the effects of taking LSD. We know what that is. It's perception alterations. We have some transient effects that resolve, mild to moderate severity.
In our study, there was one SAE in the 50-microgram arm that happened three months, actually later than three months after administration. So a profile that fits very nicely. Obviously, it's a different delivery profile in a medical setting, but one that clinically is quite meaningful and is very exciting for us. Just focusing on the 100-microgram arm in that study versus placebo, again, you see a really interesting feature is that we both saw reductions in Hamilton Anxiety scores, but also MADRS scores, which is the primary endpoint in depression programs and in our depression program. These responses were as early as we could measure them at week one. And then interestingly and uniquely in our field, really, were durable out to 12 weeks. We didn't see any sort of reversion back to baseline.
That feature has certainly gotten clinicians we've spoken to incredibly excited because we're not talking about getting better and then trending back to baseline and needing a dose every couple of weeks. If these data hold, what we're saying is that there is a many-month durable effect and maybe even well beyond 12 weeks, something we won't know until the conclusion of our phase III program. Also, for context, again, a lot of folks don't know the Hamilton Anxiety Rating Scale quite as well as they do other scales. It is sort of worth putting into context. These patients started very severe, and these are median scores represented here, but on average, on the median average, patients started around 30, very severe, ended up median in remission in the 100-microgram group. Just data that we've never seen before in treating GAD or MDD for that matter.
Touch on the AE profile. Maybe we'll transition and talk a little bit about what comes next. We're actively enrolling in our three phase III studies. The two in GAD are Voyage and Panorama. I already described somewhat of the study design for the acute phase. There are two parts of these studies, though. After 12 weeks, patients continue on into a 40-week extension period where they have the opportunity for open-label treatment with the active drug 100 micrograms of MM120. That gives us an ability to look at the real-world kind of treatment profile. What happens over the course of nine months or a year for patients who get active drug first? How often do they need the drug? How many doses of drug do they need on average? What happens upon subsequent retreatment with the drug? It's triggered retreatment.
Patients who have symptoms of 16 or greater on the Hamilton Anxiety Rating Scale will be eligible for treatment, and they can get up to four doses of drug in that extension phase. Another feature of the design is that because we do not, unlike most studies, a daily drug, an open-label extension period, on the first day of that open-label extension period, patients are unblinded. They get open-label drug. In our study, they are randomized, get a dose of drug, follow them for 12 weeks. After that 12 weeks, until they have symptoms return, we also just continue to follow them. They are still blinded. They are still randomized. We can still analyze their data accordingly. Until those patients take open-label drug, we have a longer-term randomized withdrawal or, excuse me, randomized controlled study that can speak to things like durability, that longer than 12 weeks.
We get Kaplan-Meier curves, time to hitting a certain endpoint or time to needing a retreatment, which gives us a lot of ability to argue for that extended durability of a single treatment of the drug. Emerge, I can say, copy and paste almost. The main difference here is that we have a slightly smaller study, 70 patients per arm. Out of a well-established practice in depression, we use the MADRS as the primary endpoint. We use the MADRS at six weeks. Again, this is consistent with virtually all, with FDA's guidance, virtually all the approvals in MDD. A single administration where we again follow patients for 12 weeks, have the same extension period where patients can have open-label drug. A feature operationally is that this study is also running at the same sites as our Voyage and Panorama sites.
It gives us the ability to keep patients in our studies. If they screen out of a GAD study because they're in a depressive episode, we're able to retain them and keep them and put them in the Emerge study, something that a few months ago was theoretical, and now we're actually seeing happen in practice, which is quite encouraging. From a regulatory standpoint, there has been obviously a lot of regulatory progress that we've made over the last 12 months. We've been really encouraged by comments from the new administration, by new leadership at FDA, and are seeing an incredible dialogue. We've been very fortunate with the Breakthrough Therapy designation to have very frequent and thorough engagement with the division.
I've been fortunate to work with them for the last seven years on this drug class and know the ins and outs, our program knows the ins and outs of how they're thinking about and how we need to stand up to the highest level of regulatory scrutiny and be positioned best possible if we get compelling phase III data. Another feature of our program is that while there's been a whole spectrum of approaches to the sort of patient course on a day of treatment, what it looks like to get the drug, there used to be terms like prep and integration that got talked about quite extensively. Those became unpopular and have now been rebranded as other things. From day one in our program, starting in our phase II study, we just give patients drug.
We give them informed consent, of course, as we have to do in any clinical trial, and we would expect informed consent in the real world, just like happens in everyday medical practice. What we do is then give them the drug on the day of dosing. They're kept in a monitored setting under observation. They're kept under observation for a fixed eight-hour period in our phase III program so that we don't want placebo patients saying two hours in, "Oh, I feel fine. I'm going to leave the room." That wouldn't be a good thing for trial integrity. Everything about our program has been designed to maximize the flexibility and the breadth of potential adoption if we get an approval and marketing the drug and are fortunate enough to be launching it.
When we think about our overall strategy, again, we talk about, as a field sometimes, we talk about the broad potential. We talk about the unmet need that is in the millions and millions of patients. That need has informed our labeling choices. It's intentional that we're going after the broad labels for GAD and MDD. It's also informed how we think about generating evidence for value and for the real-world treatment patterns. We have the best possible case with payers to get reimbursement, market access, and the infrastructure that, as we showed before, is already asking for this. It's saying we're really excited about a practice-changing new drug approval that we can leverage that, that we can lean into that. There is a wide, wide range of clinics that are doing interventional psychiatry today that we can leverage. There are undoubtedly others that will want to be involved.
They're already telling us they're excited about the potential and want to adapt and want to be ready to deliver these drugs if we get them approved. Another feature here is when we talk about value and we talk about the outcomes, a lot of questions we get from time to time are, "Okay, well, that's great. How does this fit into this Bravado framework that has evolved?" It doesn't, and it shouldn't. That is our view of why we're doing something different is because it is transformative. It is something that is going to align nicely with patient desires, with site economics. Of course, incumbent on us is to price the drug and come up with a contracting and a commercial framework at the end of the day that is attractive for clinics. You put the ingredients together of patients are getting better.
We get site economics right so that they're making money. The clinician experience with this is quite attractive. I mean, in our phase II study, we had investigators come to us and say, "I sat in the corner and caught up on notes for most of the day." It's not very much that's happening while they're in the room watching patients. Add all of that together. If we can drive value and drive attractive economics for sites of delivery and drive the best outcomes we've ever seen in a field, all of those ingredients are exactly what you would ask for for a sort of paradigm-shifting drug and something that we're very excited about building more and more evidence on all these facets as we progress. We won't spend a ton of time on the specifics. We've got a few minutes left. I guess happy to take questions.
Otherwise, happy to wrap up a few minutes early. All right. Everyone has places to be, so we'll let you go. Thanks so much. Oh, we have one question. All right, please.
So how's the experience of the MM120?
In what capacity?
For the patient.
Yeah, I mean, so the question was experience of the patient with MM-120. We have gotten into it's an early dissolving tablet. No, no, please.
Not the experience throughout the weeks, just the moment throughout the period of experience. Is there hallucinations?
Yes, the questions are the sort of phenomenologic aspects of it. What do patients go through? Yeah, hallucination is a word that is probably commonly used. It's not quite precisely what happens. And it's worth maybe spending one second. Hallucinations mean a de novo view that something is real that is not. There's no sensory input to suggest it's real.
People talk a lot about seeing tastes and hearing colors and things of this nature. These are more properly characterized as illusions. Yes, these absolutely happen. Where there are sensory inputs, there can be distortion. Really, this is a function of turning off the brain's filtering network. When we talk about the default mode network, that is your brain organizing a bunch of very confusing, if you walk around the streets of New York, lots of sensory inputs that we have to filter through so that we can navigate the world and live a life. That disorganization of the brain's normal filtering mechanism leads to sensory changes. It leads to cognitive changes that also allow for this sort of processing.
That is why we look at, and why we have been studying the drug as sort of autotherapeutic, if you will, that there is no sort of dietic therapy that is needed with the drug. Any drug is therapeutic, of course, but really what is happening and what we hear from patient experiences is there is some sort of processing, reframing of a person's relationship to the things that are the source of distress, of anxiety, of depression, whatever it may be. Again, as they come out of that experience, they say largely they feel sort of a reorientation to the things that were causing them distress in the past. From an observer, from the outside looking in, generally it looks like a patient is laying down on the couch taking a long nap. Occasionally, they will sit up and say, "I need water. I need to go to the bathroom.
I'd like a snack." There's not a lot that ends up happening. It is a very sort of, I mean, again, we hear a lot of historical stories and naturalistic illicit use of psychedelics. People talk about very challenging experiences and things. These are just not features of really what we've seen in the development program to date. Challenging experiences, I mean, words like bad are in psychiatry quite interesting because sometimes they're the things that drive the most insight and the most change. Certainly there will be challenging experiences that happen. There will be patients that don't respond. There will be patients that have bad outcomes, as there are with any drug. By and large, what we hear is that patients have a fairly pleasant and enjoyable experience. Many times they say, "I don't really want to do that again.
I would if I needed to. But we've been really encouraged by all that we've seen from a patient experience standpoint. All right. Thank you.