Okay. All right, thanks for joining this afternoon, the Oppenheimer Healthcare Life Sciences Conference. I know it's been a very busy time for a lot of people, so I appreciate the time. Next presenter here, we have Rob Barrow, who's the CEO of MindMed. Just full disclosure, we cover MindMed at Oppenheimer. François Brisebois. I'm one of the senior biotech analysts at the firm. With that, Rob, thanks for joining. I think what would be helpful in terms of format, we'll just do a fireside chat. I think what would be most helpful is just maybe to those that aren't familiar, just an overview of the company.
Yeah. Thanks so much, François. Thanks for having us here. To give a high level overview, we're a company headquartered in New York that's developing the psychedelic drug class. I think we've taken a particularly unique approach in the opportunity of developing these molecules. It's one that tries to utilize sort of multi-generational approach, one that, you know, harnesses both the sort of psychological mechanisms that we see more commonly used or targeted with this drug class, but also some approaches with certain molecules and dosing paradigms that don't really focus so much on a session-based delivery platform, but instead focus just on utilizing the biology. We have drugs that are potent serotonin agonists that target the serotonin system.
Our two lead candidates being our proprietary form of LSD or lysergide and the R-enantiomer of MDMA. We've got several programs in Phase II at the moment. A Phase II B study of LSD for generalized anxiety disorder that'll be reading out later this year, a Phase II A proof of concept study of LSD in a low repeat administration model that'll also be reading out later this year. We'll be going into our first Phase I clinical trial of R-MDMA later in the year as well. It's an exciting 2023 for us, coming up on some, you know, some very clear milestones to demonstrate in modern sponsored research what we've seen from many studies in the past with this drug class.
Okay, great. On the, you know, in terms of readouts, can you just mention maybe, in terms of so you have GAD, you have ADHD, but, can you talk about your MDMA program maybe on the, in terms of preclinical data? Are you expecting that this year, or just a start for next year?
Yeah, absolutely. Historically with the enantiomers of MDMA and racemic MDMA, there's obviously racemic MDMA has been in clinical development for quite some time, and our colleagues at MAPS have reported successful phase III results in post-traumatic stress disorder. With the enantiomers of MDMA, there was some preliminary research just looking at functional activity and, you know, the cellular pharmacology assays. What we see is that there's a really distinct pharmacological profile for R versus, as S MDMA. There's even some preclinical animal data suggesting that the R- enantiomer enhances or at least maintains the prosocial benefits we see with racemic MDMA while eliminating some of the more dopaminergic stimulant-like activity that is more commonly associated with racemic MDMA's use.
We took that evidence and really advanced it further, looking at various CNS disease models and particularly in areas of interest for us. Our indication that we're pursuing with that program is to treat core symptoms of autism spectrum disorder, those being primarily social communication deficits. There are preclinical models of ASD which we've utilized. The first half of this year, we'll also be sharing and publishing results from those studies to demonstrate some of the preclinical activity that we certainly hope will translate over into the clinic.
What are you hoping to see just for something that you know, you're hoping there's more of a social aspect to it? On the preclinical side, what are you hoping to see in this data?
Yeah. These are generally sort of looking for social engagement. The amount of time that these animals... Obviously the translatability is something that's critically important. We see when we're looking at drug, we're looking at the on-drug activity of our MDMA, and we're trying to demonstrate that it enhances social functioning. In preclinical models, what that means is that animals, for instance, that are, you know, have a syndrome that is either the same or similar to what we'd expect in autism spectrum disorder, which is associated with social and communication deficits. We're looking for animals that are going to be engaging more frequently, spending more time, engaging in social activities as you know, as opposed to, you know, being isolated or isolating, self-isolating themselves.
Certainly some more extensive methodology for what we studied, and the exact population will be coming out with those results. Generally what we see is in these preclinical models that when there is an enhancement of prosocial activity, there's a nice translation over into the same sort of activity in humans. Certainly given the history with racemic MDMA gives us an added level of confidence that preclinical results would have a good likelihood of demonstrating something similar in humans.
Okay, great. Just as now as we're on the racemic MDMA program, can you just talk about your collaboration with the University Hospital Basel and, you know, maybe the study that's going on over there to really figure out, you know, the difference between the enantiomers?
Absolutely. One of the key features early in MindMed's formation was a collaboration with Dr. Matthias Liechti at University Hospital Basel. They've been doing extensive work with the drug class of psychedelics, with LSD and MDMA for many years now. As part of that collaboration, it gives us really an opportunity to de-risk our clinical approach and get some very early clinical data and explore some things that, you know, it would be more challenging to explore in a sponsored research program. That study that you mentioned is a comparative PK/PD study which we're actively enrolling through our partnership with University Hospital Basel. What we're looking to demonstrate are the differential pharmacodynamic effects.
All these things that we're seeing pre-clinically and seeing in terms of the pharmacology of these molecules to see how that translates over into humans. Really what we're interested in is looking at both racemic MDMA, which again, has been well-characterized in a comprehensive development program by another organization. Looking at those distinct perceptual and acute effects for the R versus the S enantiomer. Certainly when we're looking to treat something like autism spectrum disorder and we're trying to see enhanced prosocial effects, this is something that has been reported with racemic MDMA's use historically, right? It's thought of as an entactogen and talked about in terms of the enhanced connectivity that you see within MDMA's administration.
That's really been our approach with the R-MDMA program is to look for those on-drug effects. This opportunity to get in very early and demonstrate whether, you know, the different kind of profile we see and to start characterizing the pharmacokinetics of different doses of R-MDMA as well, to give us some really important insights and allow us to try to get, you know, early evidence that we're seeing the desired clinical activity as soon as we possibly can in development.
That's great. Well, it's very interesting that you're going into ASD. Seems like there's nothing out there. It's not super understood. Maybe if you can let us know why you chose autism spectrum disorder.
It has a lot to do with what we already know about the these molecules and what we've been able to demonstrate pre-clinically that we see because there is such a marked increase in social activity and social and thought of as prosocial effects. That is really sort of functionally at the heart of where we see a deficit and where the focus for regulatory programs that have been developed previously, for instance by Roche, had a phase three program and a Breakthrough Therapy designation targeting Autism Spectrum Disorder. When we looked at the activity functionally of R-MDMA, and we look at the opportunity where there are no approved therapies to treat core symptoms of ASD, only for comorbid conditions and agitation in ASD.
We think there's an enormous market. Autism costs our healthcare system $460 billion a year. The opportunity to help the patients who have absolutely nothing, we see that the pre-clinical effects and what we believe will be the pharmacodynamic effects of R-MDMA also align very much with what patients report desiring in that population from pharmacotherapy. You know, for us, it represents really an untapped area, an area where we could have an enormous impact and one that is so closely aligned both in terms of the mechanisms of action of R-MDMA, but also in terms of functionally how the molecule behaves pre-clinically and how we believe it will ultimately translate into human activity.
Great. Okay, great. You just had your quarter recently. It seems everything's on track. Clearly, I mean, the big program this year is MM-120 for Generalized Anxiety Disorder, GAD. In terms of that program, can you just maybe to start why there's been a lot of hype, of noise and you know, ultimately I think in this space, the data will, you know, tell the story itself. I guess here, why LSD as a molecule over others that are used? Maybe if you could touch on, you know, it seems like there's a lot of study on it. There's a lot of information about its durability, its potency, its PK/PD. Just what's the background of LSD versus maybe others that people are using?
Yeah. It's really important to highlight that LSD is in this drug class, in psychedelics, LSD is the most extensively studied molecule. It's the most potent molecule, but by a factor of many. I mean by a factor of something like 200 over psilocybin. It's also a molecule where we've seen over 20 studies historically in anxiety, depression, and neurotic illness where there's you know, a consistent positive clinical response. This is in hundreds of patients. It's been studied in clinical trials alone in over 10,000 patients historically.
When you look at a drug class and you look at the molecule where there's the best information, you have consistent signals of clinical activity, and you know so much about it really stands out in terms of the opportunity to bring the therapy forward. You know, certainly we've seen our colleagues, I think it's always perhaps overlooked, but our colleagues in Switzerland have under a compassionate use program, have a ability to treat patients with a number of these molecules, and many of them, you know, choose to use LSD.
We've heard other, you know, anecdotally, a lot of commentary about why LSD is such a preferred molecule to study it and the likelihood of seeing those profound acute effects that are so highly correlated with clinical response. We believe that LSD has the greatest chance of success in terms of imparting on a, you know, reliably inducing the kind of acute effects that will then lead to improvements in things like anxiety, depression, and other CNS disorders.
What is from a patient's perspective, maybe more anecdotally or whatnot, is it clear from the patient's perspective if he's receiving psilocybin versus LSD? How is the experience different?
That's a really interesting question, one that's somewhat difficult to answer, of course. You know, would obviously rely on sort of self-reported qualitative perceptual effects, something that, you know, really is, I'd say would be hard to do reliably. Certainly the activity at a cellular level and a signaling level is not all that different, although you do see distinct binding patterns. You see, you know, in terms of other, the subtypes of the serotonin receptors that you're engaging. We believe that the perceptual effects and the acute sort of hallucinogenic psychedelic effects are driven by serotonin 2A receptor and you'd see engagement both from psilocybin and LSD.
There's been some studies looking at, you know, the comparative effects between the two, but it'd be a little bit, you know, getting a little bit ahead of ourselves, I think, to try to draw too many conclusions. We do know is because of LSD's potency and because of, I think, the clinical design we've taken forward into phase II, where we're looking at a full dose response up to doses that would be the equivalent of, you know, a multiple over what has been studied with psilocybin in most of the programs that are being developed today, you know, we think that gives us a great opportunity to, on average, see a more likelihood of generating those acute effects.
Again, those are so highly correlated with clinical outcomes that we think LSD both stands on its own, but also just because we're testing such a broad range, we'll have the greatest insights in terms of the right levels and the activity that we can ultimately drive to a phase III program.
Great. In terms of some of the data that's coming out of phase II B, you're saying before year-end, late this year. In terms of expectations, you know, what can investors look at to help feel confident about the outcome here? Maybe if you could touch on, you know, there's historical data, but there's also last year data that came out of your collaborators there at University Hospital Basel, you know, IIT study. Those phase II results, maybe if you could touch on, you know, the design and the data that was shown there.
Absolutely. I think that's always one of those data points that's critically important. We've so much historical information, but those studies are from the, you know, prior to the Controlled Substances Act, which came into effect in the early 1970s. We always take those legacy data and want to confirm them with modern methodologies and modern study conduct. That's where the our colleagues at University Hospital Basel, as you mentioned, last May published results where they administered two doses of 200 micrograms of LSD to patients who had anxiety disorders, including generalized anxiety disorder. What we saw is was consistent with that historical evidence. We saw a rapid and durable response, and it was a crossover study design.
You know, the response, the anxiolytic effects were present as soon as we measured them after dosing. Even after the first dose, you saw a significant reduction in anxiety symptoms. Overall, we saw about a 65% response in the active group versus a single-digit response in terms of patients who achieved 30% or greater reduction in anxiety symptoms between the placebo and the active group. 65 versus nine is a pretty staggering difference. We also saw that even though it was a crossover study, at six months patients were crossed over, so those who got LSD first subsequently received placebo, the patients who did receive LSD first demonstrated reduced anxiety symptoms out to a year after baseline.
Both the acute and durable response, it just supports that historical evidence and gives us a high degree of confidence that the study we're conducting that includes the highest dose being tested is 200 micrograms. We certainly believe that those more modern confirmatory data give us a greatest chance of success in our phase II B program, and gives us an opportunity to nail down our dose and then have a very efficient pivotal program.
Great. People with depression, with MDD and people hear about the MADRS scores a lot. Can you just talk about what the endpoint is for GAD and how validated are those endpoints?
Yeah. The endpoint in anxiety has been used for effectively all anxiolytics is the Hamilton Anxiety Rating Scale. In depression obviously we have the Hamilton Depression Rating Scale, and we have the MADRS, Montgomery-Åsberg. Every drug that has been approved in anxiety has used the Hamilton Anxiety Rating Scale (HAMA), that's exactly what we'll be using in our program. The study out of UHB last year did use a slightly different endpoint that is highly consistent with the Hamilton Anxiety Rating Scale. Certainly we're looking very closely. It's also really important to highlight that our Phase II B program, you know, from day one we've tried to take a very rigorous approach and not, you know, make sure that we're making valid assumptions and not, you know, inflating our expectations.
That's really important that we set our expectations appropriately for what this drug class can do. We've powered our Phase II B study so that even if we saw a similar or just a marginal improvement over the effect size that's there for the standard of care for benzodiazepines and SSRIs, you know, we would be powered to detect a difference in our study. You know, certainly historical evidence, we're seeing a reduction in anxiety symptoms that's two or three times greater than standard of care, which again, gives us a high degree of confidence in the likelihood of success with this study.
Are you looking at repeat dose like they did in the IIT study from UHB or no?
Not currently. Certainly one of those interesting questions that will need to be answered at some point in development, or, you know, in a post-approval setting is exactly what a retreatment paradigm looks like, right? I mean, these no matter the condition, it's not our expectation, I don't think it should be anyone's expectation that this is a one treatment and it's curative. That would be a, you know, an unrealistic expectation for any drug treating a CNS disorder. We're certainly focused on how to demonstrate that appropriately. Given the durability of activity we've seen, for instance, from the UHB study last year, you know, I think that opens up a lot of opportunities for later, you know, downstream, later in development, exploration of what repeat administration looks like.
In the UHB study they did use two doses of 200 micrograms. We really saw that the magnitude of response was there after the first dose. We want to characterize what happens after a single administration, and certainly think that a single administration from a commercial standpoint obviously is, you know, half the amount of doses means half the amount of time delivering these treatments.
That's interesting because Yeah, the time on that's an interesting point you bring up because that's a big, you know, a big point of debate in terms of the duration of treatment. Although, obviously, if it's more durable, there's less treatment. Maybe if you could tie that into what have you learned from Spravato, and when you look at other analogs in the space, you know, in terms of the whole delivery of care discussion of time on treatment, maybe compare and contrast to Spravato and how that's happening and just your learnings from it.
Absolutely. You know, Spravato is one of these in some circles it's talked about as a psychedelic, but it most clearly is not, right? I mean, these are dissociative anesthetics effectively that have been repurposed as antidepressants. We are seeing it's really important to highlight the fact that the commercial dynamics of Spravato, when you talk about S-ketamine, you can't ignore the fact that we have a highly genericized racemic ketamine that is, you know, very easily accessible. The dynamics of delivery and the interplay between the infrastructure and uptake for ketamine versus S-ketamine, and I think we have to look at them in a combined fashion, right?
If we look at what has been the growth in ketamine and Spravato's use and what has been the infrastructure build-out, if you look at them together, it's really been quite staggering. We've seen an enormous growth in the number of physicians, the number of clinics, the number of prescriptions, both for Spravato and for generic, you know, racemic ketamine. There isn't a perfect analog there. We certainly think it represents, you know, when you have a novel treatment paradigm that comes into an area like anxiety or depression where there's such a major unmet need and the available therapies really don't work well over time for patients, you know, when there's a new treatment, the infrastructure has demonstrated by ketamine and S-ketamine that there will be adoption.
We see this all the time in our provider engagement and our patient engagements from key opinion leaders. There's such a desire for a new form of treatment that can have a rapid and prolonged effect, and that's exactly what we're seeing in the preliminary clinical evidence for our drug. We certainly look externally and, you know, it's, we have yet to find an example where you have really a game-changing therapeutic to treat a highly prevalent disorder that there is a major unmet need for. We've yet to find one where you have a new therapy that works incredibly well that hasn't gotten, you know, taken up into the market.
While we are looking over the course of this year to further refine our pre-commercialization strategy to engage with payers and providers and make sure that we have an innovative care delivery model that will ultimately allow accessibility and get these drugs out to the patients who need them at scale, you know, we certainly believe it is a matter of execution, but it is a very surmountable challenge.
Interesting. Then, you know, I have to ask you this question because it comes up all the time. It has been coming up for years in this space. How do you view IP?
W e view Intellectual Property, I think like any other pharmaceutical company views Intellectual Property, which is to say that it's critically important, and it's critically important to know where it fits in a delivery paradigm and how it serves to protect a market. Obviously one of the most relevant and the most critically important aspects of Intellectual Property in developing novel drug candidates is what gets listed in the Orange Book, and that offers you. First of all, it should be, you know, a baseline expectation. LSD, for instance, has never been approved by FDA before. Here in the U.S., that gives us certainly a likelihood and a baseline expectation of getting marketing exclusivity when we're ultimately submitting our NDA, if we get an approval.
Beyond that, getting patents listed in the Orange Book is critically important because it offers opportunities both to immediately delay the entrance of generics by, you know, you get an automatic 30-month stay. We also just see, you know, in reality, sort of a de facto timeline when you do have Orange Book listed patents, pushes generic entrants out typically more into the 8-10 year timeframe. We've seen this over and over again. There's so many products on the market where composition of matter has not been available, and I think we look at other instances like combination products, for instance, you know, Axsome's new therapy that's obviously gotten a lot of visibility.
It requires us to be very thoughtful about our development approach, and every decision we make in terms of our R&D strategy is informed by how we can make sure we get appropriate intellectual property that will actually be protective and that will differentiate our product and will offer an important improvement over what's already available. LSD was discovered in the 1930s. We do not have composition of matter patents on it, but what we do have are sort of a multi-layered approach that we've, of really over the last 12- 18 months in particular, have had a lot of discoveries, a lot of learnings, and have filed multiple patent applications we believe will be important to protect our market and also represent, you know, an actual innovation on our products we're gonna take to market.
It seems like you mentioned, in our last couple of minutes here, you mentioned more details to come on the commercial strategy or pre-commercial launch or pre-commercial, you know, strategy, I guess, or thought process to deal with the market. What, what do you share at this point in terms of your commercial thoughts? Then, you know, how much more can we expect this year, is it in the next few years? Where, where do you ultimately want to let investors in on your commercial strategy?
Yeah. Certainly, I mean, it'll certainly be an evolving situation over time, and by the time we, of course, get an approval and are launching a product, it's going to be very clear, I think, to everybody exactly what we're doing. I mean, at this stage, what I can say is that. Our, you know, our conviction about how to approach our product candidates and the entire drug class from day one has been that we have to take a view that is going to be scalable. We have to work with a delivery model that will ultimately incentivize providers to prescribe and ultimately deliver the therapies we're developing.
At this stage, you know, really it informs everything about how we are approaching the delivery model, how we think about the psychosocial support and the container that surrounds the delivery of these therapies. You know, really, while there's been a lot of historical talk about, you know, assisted therapy or assisted psychotherapy, our view from day one is that certainly psychosocial support is an element that's going to be critical. We're big advocates for any sort of care for patients who have psychiatric disorders, and our chief medical officer is a psychoanalytic psychotherapist.
What we want to demonstrate very clearly is we have a standalone drug effect, that our products can work on their own, and that would lend itself to easier adoption, and ultimately that we're gonna have a model that will be more user-friendly for patients, for providers, and give them a real incentive to drive uptake beyond just the compelling clinical data.
Excellent. That makes a lot of sense. big, big year for MindMed. Just I guess in closing, any comments, maybe if you could tie in the cash position, and then just, you know, how comfortable you are given everything that's going on, with the market these days, and then just any closing comments or something maybe we didn't touch on during this call?
Yeah. No, thanks. It's an incredibly exciting year for us. I think, you know, we've got the LSD-GAD program that will read out late this year. We've got our LSD program in ADHD, which is an entirely different dosing model that will also read out later this year. We're gonna be in the clinic with our MDMA program in autism later this year. This is really a transformational year for us, where we should have some big leaps ahead in our programs. We did just report year-end earnings. We had about $142 million of cash, which gives us a runway out into the first half of 2025.
We're, we feel very fortunate and appreciative for all the support we've received across the board and for everyone's effort to get us where we are. Over the next 12 months, want to deliver on some really key milestones that should propel us forward into that leadership pack in the organizations that are developing this drug class. We're, we're excited about what the year holds.
That's great. Well, thank you so much, and thanks for everyone, listening in. Appreciate it. That'll be it for us.
Thanks, François.
Thanks.