Good afternoon, everyone. I'm Sumant Kulkarni, a senior biotechnology analyst here at Canaccord Genuity, and it's my pleasure to have MindMed here with us today. They've had some spectacular data fairly recently, and they're doing a lot of things. Recently announced some more trials that they plan to start. It's all coming to a head here, so thanks to Rob Barrow, CEO, for joining us, and thank you to everyone for coming and for tuning into the webcast. So the way we'll do this is, Rob will give us a few remarks just to set the stage, and then we'll go straight into Q&A, if that's okay.
Perfect.
Turn it over to you, Rob. Thanks.
Perfect. Thanks so much, Sumant. MindMed clinical stage development company. We're working on two products in the clinic. MM120, which is a form of LSD we're developing in generalized anxiety disorder and major depressive disorder. As Sumant mentioned, we had phase IIb data earlier this year and received a breakthrough therapy designation from FDA for the program. Now, coming out of a phase II meeting earlier this summer, we're in a position to launch two phase III programs. First, in generalized anxiety disorder and in parallel, a program in major depressive disorder, which will be starting later this year in GAD and in early 2025 for the MDD program. Second program in the clinic is the R-enantiomer of MDMA, which we're developing in a very different model.
So our MM120 program is come to be more familiar to the field as an acute intervention, a single dose, where we see multi-month durable effects from our phase II data. Our model for MM402 for R-MDMA is akin to how psychostimulants are administered in ADHD, which is that the on-drug effects are what we're after. We're not trying to have a disease-modifying effect. We're developing that molecule in autism spectrum disorder and in a phase I study currently, and looking to move pretty quickly into phase II early efficacy studies to demonstrate if we see any of the functional activity that we're trying to observe in the autism population. So a lot to be excited about.
We're coming up on three phase III catalysts, which will be across the year of 2026, and certainly a lot of excitement in the field with other clinical readouts and regulatory milestones in the coming quarters.
Okay, thanks for that, Rob. So I know you had your earnings call this morning. There was a lot of focus on this, and we've got to ask it anyway because it's kind of the topic du jour. How do you see the outcome of the Lycos FDA interactions recently, the action date, all of that, how all that played out, and how has that specifically impacted your plans on your Phase III clinical trials?
Yeah. So to set for anyone who isn't familiar, I think most are now, you know, Lycos Therapeutics, another company in our field, historically was called MAPS Public Benefit Corporation, was developing MDMA-assisted therapy. And that dash AT part of the equation, I think is especially impactful, for post-traumatic stress disorder. Recently came to a PDUFA date where they received a complete response letter. Certainly, a lot of discussion in our field. There was an ad com earlier in the summer as well. The reality for us is that from day one in our program, we've taken a very different approach that is on the other end of the spectrum in terms of using psychotherapeutic interventions.
Our program is oriented around giving patients our drug product, and trying to drive a meaningful benefit just from the drug without any additional psychotherapeutic intervention, which really has allowed us to avoid many of the complexities that led to an unfortunate outcome for the MDMA-assisted therapy program. As we've kind of talked about and conceived of the advisory committee, which ultimately carried through to the CRL, the big sort of broad impact topic or topic of interest is functional unblinding, which we can certainly get into. It's something that has, you know, come under a microscope for our field, but really is not all that unique in psychiatry. I mean, we look at other historical precedents, SRIs, benzodiazepines, you could... Spravato, that's kind of meaning.
All of these drugs suffer from the reality that drugs that affect the brain tend to have a perceivable effect. So 2 milligrams of Xanax is a perceivable dose of Xanax that drives an anxiolytic effect because the drugs work by how patients feel them. Very much true with our drug class, and something that we go to great lengths to try to mitigate and address in our clinical trial design and the way we operationalize the studies. We don't add in, but when organizations and research programs add in therapy on top of functional unblinding, we end up with a situation where the intervention is actually dependent on the blinding status, which creates a huge problem, which ultimately I think was a big driver of concern.
So really, when we look at the potential carry-through, we've already gone to great lengths to address this. While an unfortunate outcome for that program certainly hasn't really meaningfully changed anything about what we're doing because we've had the benefit of early and proactive engagement and alignment with FDA, and continue to build on that as we go forward into our phase III program.
So I'll start with a bit of a general question that's somewhat specific, because you have MM120 in development for both GAD as well as MDD. That's generalized anxiety disorder, as well as major depressive disorder. Sometimes depression and anxiety are two sides of a coin. Going back decades, anxious depression was the term that was used. So do you have any reason to believe the length of an episode of depression is different versus length of an episode of anxiety, if they are indeed episodic?
... It's actually a really important distinction. I think when we look at the two indications, there's a huge degree of overlap, both in terms of diagnostic construct, but also in terms of diagnosed comorbidity. 60% diagnostic comorbidity, more like 80%+ in terms of diagnostic overlap, the symptoms that represent GAD and MDD and the scales that we use to measure them. One of the defining differences, though, is that major depressive disorder is definitionally episodic. Patients have to have periods of euthymia in order to be diagnosed with major depressive disorder. They go in and out of depressive episodes. They can either be in a depressive episode or not.
Anxiety is a more chronic sort of underlying state that lasts years or a lifetime, and there aren't episodes. Patients who are diagnosed with GAD typically are thought of as having GAD for the remainder of their life, and their symptoms may be well controlled or may wane, but fundamentally, the diagnosis of GAD is not episodic. So the other sort of defining difference is that it's somewhat of an orientation to time, that anxiety tends to be forward-looking. Anxiety, generalized anxiety disorder, tends to be a cause of psychological concern about future events and how they may impact a person. And major depressive disorder typically tends to be backward-looking, worries about events of the past that have led to occurrence of psychological disorder processing challenges.
So really, when we look at the opportunity from a development standpoint and the commercial opportunity, one of the real promises is that there are two sides of the coin in so many instances, and that for care providers, one of the big opportunities is that a patient walks in the door, and regardless if they're predominantly suffering from anxiety or depressive clusters of symptoms, if we can end up with a label where both are covered, providers have the confidence, hopefully then to you know know exactly where to put the patient, where many of the other programs have been sort of siloed into only refractory depression at this point. So in the long run, we think this gives us a better opportunity to bring more patients into availability for treatment with our drug.
So this is a really great way in which you delineated MDD versus GAD. So with that as background, do you have any reason to believe that there's a mechanistically different effect of MM120 in terms of durability of effect in MDD and GAD?
It's a little premature to say until we till we get to the later stage controlled studies and look at durability beyond what we have so far, which is 12 weeks. One, you know, we have a pretty huge body of literature on depression, though, with studies like STAR*D, and this is just epidemiological and observational for current standards of care for SRIs. And what we see there is that the patterns of major depressive episodes are such that some patients only have one depressive episode in their lifetime, and then either are well controlled or just naturalistically never have another. And so one can certainly conceive of a...
In such patients who only have 1 or 2 episodes, if you can terminate that episode, then there would be an indefinite potential response thereafter, whereas GAD is a chronic diagnosis. What we've seen so far, though, both from our data and from our collaborators and sort of real-world data that's been generated in compassionate use programs, is that the durability in both disorders can be pronounced even after a single dose. We've seen 3+ months, and in some studies, years of benefit, where patients, for instance, in our phase II study, about half of patients were in remission 3 months after a single treatment. In some of those other studies, again, the durability can last for 1 or 2 years or even longer.
So going to your trial design that you announced today, there's up to four open-label doses of 120-
That's right
... in both trials, right?
Correct.
Which one would you expect, patients to use on average or as a median, less number of re-treatments, MDD or GAD?
It's an answer that we certainly have a great interest in characterizing and understanding, but that's why we're gonna do the study and truly try to granularly define it. I think, again, based on response patterns and based on the reality of the diagnoses, there's a likelihood that in chronic conditions, over time, whatever that interval may be, that there would be a need for additional treatments, but that may be, in some instances, the course of over the course of many, many years. What we seem to come to time and again in our data and in data around this molecule, is that it's not so much a symptom-blunting effect as we see with current standards of care.
It's more about sort of reorientation, almost a phase shift for patients, such that they end up in a new state and don't seem to show any sort of on average reversion in either, you know, either back to baseline or in any direction, such that based on the data we have, the high-quality data we generated in phase II, we don't have trend lines pointing to worsening or further improvement after 12 weeks. So, something we're really interested in characterizing as we get out beyond three months in time.
So I'm enrolled here asking questions that are too early to answer, so I might as well ask this one, which is, you know, it's, you're just starting a phase III program. We have phase II data. Typically, when products go from phase II to phase III, there's, for lack of a better term, a haircut on efficacy. What would you guesstimate would that haircut be in the GAD context relative to the GAD data that you have in phase II?
... Well, so yeah, going, going back to the phase II data as a starting point, we again demonstrated about a 50% remission rate 12 weeks after a single treatment that corresponded with a 21-point reduction from baseline, and an effect size, which of course, gives us sort of ease in talking about these things of 0.8, more than double the standard of care. As we've approached our phase III program, we have designed it to detect an effect size of about 0.5, which assumes that we're gonna get a haircut. Now, we have a lot of reasons to believe that the placebo response we observe, I mean, a lot of times that haircut happens because placebo responses grow. What we saw is that in our phase II study, it was a 5-arm study.
Patients had an 80% likelihood of getting a dose of drug, and as a result, a third of our placebo patients guessed that they were on drug, even though they were not. That led to a really outsized placebo response, about a 14-point improvement from baseline, compared to a historical average of about 9 or 10 points. So if we see as we go into head-to-head studies, if we see a more normalization of that placebo response, that would certainly give us an opportunity for even more separation. But again, that said, we've assumed that we'd be able to pick up a 5-point difference or improvement over placebo.
We have 90% power to do so, and of course, if we saw even an improvement that was 3.5 or 4 points over placebo, would be designed to then result in a statistically positive study. And we've also made the assumption that if we see. We have a blinded interim sample size re-estimation, such that if we see in our GAD studies an increase in dropout or higher variability than we expect, we'd be able to increase the sample size in the phase III studies by up to 50%, so we maintain the 90% power.
So we've done everything possible and have a high degree of confidence that if we see a clinically meaningful response, even if we do have a reduction in the effect size, that we would then be able to come to successful studies.
So on that high degree of confidence, GAD is typically a very heterogeneous patient population. So, how do you ensure that you get the right type of patient into your phase III trial?
Well, we go to great lengths to recruit, and, you know, ultimately it comes down to site reliability. You know, our team has great connectivity to really experienced psychiatric research sites that drive, you know, patient diagnosis. We also use independent raters for disease severity. That's important both for diagnosis, but also for maintenance of the functional blind in these studies. And then, we're also using a third-party independent verification of diagnosis, such that we ensure we are getting patients who have GAD. That's the primary cause of clinical concern, and again, to the greatest extent of it, I think any study have confidence in the population they'll be getting.
This might sound like a question that makes me wanna make my life easier in terms of financial modeling, but it's not. It has really important commercial implications. What do you consider the ideal durability for MM120 in GAD and MDD?
I think fundamentally, our view and our... You know, the ideal here is to help patients get better. So as long as durability is possible, certainly what we're hoping to demonstrate. The reality is, this is likely an episodic treatment paradigm, one where, you know, we don't expect to be in a world in a post-approval setting, where patients are taking the drug on a fixed interval at every X number of months or years or whatever it may be. This would be more akin to an antibiotic or something, where patients have a reemergence of symptoms and then need retreatment, and that interval between retreatments is going to be variable, variable by person.
The best data we have today suggests that we do have really compelling support for long-term durability after just an acute treatment. So if we can demonstrate three months or longer, we think that is certainly something that would be incredibly compelling from a use scenario in both indications and part of the reason why we've established our primary endpoint at 12 weeks in the GAD studies.
So there's lots of variables with durability right now, right? Because you have to generate the data to know exactly what that might be in the first place. But we do have some products that proved in the MDD context. We have products approved for GAD. So when you think about an eventual pricing paradigm, do you consider annual branded pricing of those kinds of products and then sort of back into what you would want to do for your product? Or how does that work when you're internally doing your math?
Yeah, it's a great... We generally think of annual pricing, you know, across the board as just the sort of practice and what makes comparability possible, for you know, any drugs for HEOR kind of argument. So when we think of the costs of Spravato, say, versus a branded SRI, we don't talk about the per unit cost. We do talk about the per unit cost, but at the end of the day, what we're looking at is total annual treatment costs.
That's where, when we stack up the data we've seen and the kind of economics we could ultimately derive from that, if we have a drug that needs to be only administered a few times a year, and we compare that to the costs of overall care for patients who are taking daily drugs and not responding well, or if we compare it to things like J&J's Spravato, which requires up to 56 treatments a year, 112 hours of monitoring, and has a price tag of $25,000-$62,000 a year list, we come up with a really attractive, you know, comparison and a really attractive pricing opportunity.
So, given the difference, like the chronic nature of GAD versus more episodic nature of MDD, you have the same dose, dosing paradigm in both indications. What does that mean for the potential to price things differently in those two indications, or is there no potential to do that?
We think that there's certainly gonna be value derived from, you know, treating patients in both GAD and MDD, and that collectively, if we are able to show benefit in both of those sets of symptoms and diagnoses, that we'll be able to really make strong HEOR arguments. So when we think of, you know, we do think kind of holistically about caring for patients, regardless of the indication. And again, I think regardless of the sequencing of those approvals and where they land in discussions with payers, would be a really wide range of opportunity because of the costs that both of these indications represent.
Let's fast forward to a time, let's say, that MM120 is approved for both GAD and MDD. What do you see are the key commercial challenges that you'll face?
Well, certainly, we're seeing an evolving infrastructure to adopt these. I think at face, when anyone looks at the, the drug class and the opportunity commercially for the first time, this isn't how psychiatry has been set up historically. That's a good thing for us, and there needs to be a change. If the treatment options we had today were working so well, we wouldn't have the kind of growth and the kind of numbers we see in both GAD and MDD. So we really look at that as a meaningful indication that we are onto something that is going to potentially have a lot of progress. You know, that there's certainly millions, tens of millions of patients that could potentially benefit from these treatments.
When we look at, again, Spravato as an analog, there's about 45,000, excuse me, 4,500 treatment centers around the country. So in order to treat all of the patients, we would need more centers and more providers. We don't think that necessarily everyone who has GAD or MDD is going to take MM120 one day, although, again, we, we wanna make this option available as, as widely as possible. So, certainly building out the infrastructure and making sure there's a, a recognition of, the clinical data. These are...
LSD is a drug that has its own, you know, history and sort of socially and medically, and so we wanna make sure that the world is ready and that the infrastructure is ready to adopt these if we're really driving the kind of long-term benefit that we've been able to show so far.
So this is one of those purely stock analyst type questions, right? So you've had good data, you've had the benefit of interactions with several investors now, given you've raised capital a couple of times, at least. What's the best comeback you have to a quote unquote "biotech investor" who says, "I like the stock ahead of data, but I don't want to stick around for commercialization?
My answer to anyone who would think that is that they're going to miss out on an opportunity, because we certainly see a huge opportunity. We think this is going to be a really meaningful change for patients, and given the economics, given the burden, and given the prevalence, you know, when we kind of look at any opportunity as financially or as a business, we start with wanting to make sure we can help patients in a meaningful way. And then we start looking at all the factors that would need to be lined up in order to enable adoption. And really, that's where we see all of those factors converging. You know, the treatments we don't have are not very good. The numbers of patients are absolutely, unfortunately, extremely large.
The infrastructure has adapted, and it's continuing to evolve in favor of this. We have enthusiasm from providers and from patients, and data suggests that, you know, a good majority, a vast majority of psychiatrists, especially those that are familiar with the research, believe this is going to be a real game changer, a sort of paradigm shift in psychiatric care for mood and anxiety disorders. So all of those factors converge around an incredibly exciting commercial opportunity, and there have been many instances in you know, drug development and biotech where the commentary is that things can't be done until they can, and all of a sudden, when they can, certainly they prove themselves out, and that's certainly what we're hoping to achieve here as well.
Yep, point well made. So now that you have, like, the trial design, you mentioned there was a key thing there, 12 hours-8 hours, dosing-wise. What led you to take that step? What made you take that step in terms of your ability to pull that off, and what's the key bottleneck that might prevent you from going even lower than 8 hours?
Well, we're gonna be guided by the data, and the thing we've done across our program on that issue and on many others, is to really take a proactive, data-driven stance in any arguments we're making.
So when we have embarked on our phase II program, we came up with a structured set of criteria that we presented to the agency and said, "Here's how we're going to determine when a patient should be allowed to leave the dosing session on the day of dosing." We ultimately collected those data, kept everyone in the clinic for 12 hours in phase II, but started assessing on an hourly basis at hour 8, and we came to the data at the end of the study and presented those data and said, "There's not a good rationale for keeping patients in longer than they need to be, and a really substantial portion of patients should be allowed to go much earlier." We're taking the same approach, although we've been informed by the data to further refine and really streamline the criteria that would be required for a patient to be able to depart a dosing session.
We'll be assessing that as early as hour 5 in our study. We'll keep everyone in, you know, under observation for 8 hours, but start collecting on an hourly basis at hour 5. That would give us then the data, and after we complete the study, to go and say, you know, X number of patients are able to leave at Y point in time.
We certainly believe that from a patient safety standpoint and a recognition of the burden of keeping patients in a clinical setting for longer than they need to be, a fixed monitoring interval should be as short as possible, and then it should be left up to, you know, a well-defined set of criteria that investigators and the real-world practitioners can use their discretion to determine when a patient is safe to leave.
So we're almost out of time, so I'll ask a 402 question. Given you have two very large registrational programs ongoing with 120, how do you prioritize the level of focus that you might need on the 402 program in autism spectrum?
It's a really exciting program, of course, in phase I, and we look to move quickly thereafter into early efficacy studies in the autism population, but an incredible opportunity to have a long-term impact there. That program will be, you know, paced at the right rate, so that it complements our pipeline and that we're being thoughtful. We also recognize the need for sensitivity, both around the way that we're trying to develop that molecule, but also in the population that we're pursuing, and all that will need to be done to get that right and to make sure that it integrates with patient desires and needs. And so, we're gonna be really thoughtful about that, and certainly laser focused on getting our phase III readouts in GAD and MDD.
Thanks, Robert. I think we're out of time, so thank you for making it. Thanks to everyone for attending.