Hello, everyone, and welcome to the fifth annual HC Wainwright Virtual Neuro Perspectives Conference. My name is Patrick Trucchio. I'm a senior healthcare analyst at HC Wainwright, and I'm your host for the conference. We have a robust agenda for the conference this year, with more than 20 companies presenting, with their sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats on the day of the conference, June 27th, with a broad neurology focus across a plethora of indications, from depression and epilepsy to Alzheimer's disease and ALS, along with novel methods of drug delivery to the CNS. This is by far our strongest agenda ever.
So with that, it's my pleasure to introduce our next speaker, Rob Barrow, CEO of Mind Medicine, a clinical stage biopharmaceutical company developing novel product candidates to treat brain health disorders, starting first with lead candidate MM120, and generalized anxiety disorder, or GAD. So maybe first, if we could, start with maybe telling us more about MindMed, the founding of the company, and what differentiates MindMed among others in this mental healthcare space.
Yeah. Well, first, thanks so much for having us, Patrick, and I look forward to the conference. MindMed was formed in 2019, but really sort of had a reformation in early 2021. Since that time, we've really rebuilt the company from the ground up with an entirely new set of employees. We're now around 60 or 65 employees, and board of directors, and over that time, we've launched our clinical programs, advanced those through into the clinic, and obviously with our MM120 program earlier this year, announced incredibly positive results from a phase II study of MM120 in generalized anxiety disorder.
One of the really sort of foundational principles for us about developing the drug class of psychedelics that we're primarily focused at the moment is to do this in a way that allows for broad accessibility and commercialization. So we can do this at scale if we're fortunate enough to get these products approved and marketed. That means things like eliminating any form of assisted therapy or psychotherapy from the delivery of the drug class. So we work on MM120, LSD, which we are developing in a number of psychiatric disorders. In that setting, a lot of the other historical programs and a lot of the other growing programs have focused on this model of psychedelic-assisted therapy, or some have called it psychedelic therapy.
Our approach from day one has been that we need to develop these drugs like any other drugs. We need to eliminate the sort of therapeutic element outside of the drug's activity from clinical trials. Now, obviously, that's a different thing than what will happen likely in the real world, but from a regulatory and clinical development perspective, we need to develop the drugs as standalone treatments. And that's what we've been able to do really uniquely in the field, and have also been incredibly fortunate through that to deliver positive results, even even with that approach. So we're heading into phase III clinical trials later this year for MM120.
We also have our second program, which is the R enantiomer of MDMA, MM402, which we're developing in autism spectrum disorder, with an entirely different model, one that is not reliant on inpatient delivery or sort of a disease-modifying approach, but more like a standard drug. The analogy we like to draw is how psychostimulants are used in ADHD. So this would be a regularly administered product that would be targeted to aid in social communication skills in the autism population.
Yeah, terrific. Yeah, and it's really interesting because I think MindMed did have a very differentiated approach to clinical development of MM120 in particular, and I think some of the design elements, I think, have proven to be advantageous. So, we'll get into some of those one by one a little bit later. But I think first I wanted to just go back. On May 8th, MindMed issued a corporate update. What are the take-home messages from that update for investors?
Well, really, you know, where we are today and where we're headed as an organization, as I mentioned, is into the phase III clinical trials, and so as, you know, overall as an organization, we're positioning ourselves to be a pre-commercial stage organization, to execute on two phase III clinical trials starting later this year, and we'll continue to evolve the organization and make sure that we are positioned for success as we enter this later final stage of development.
And as we're, you know, just moving to MM120, maybe just to kind of level set everyone as far as... You know, I think most folks have some familiarity, at least, with what LSD is, but maybe you can talk a little bit more about MM120 and what makes this a differentiated psychoactive compound.
Yeah, absolutely. Many people do know what LSD is. It obviously has a place in the sort of social history and medical history and psychiatry here in the United States. The reality is that this is the drug that was most extensively studied before the Controlled Substances Act in the entire drug class. It's the one that's the most potent, we think that has the strongest clinical evidence to date. What we have done, and a lot of the innovation, has been to develop a formulation that can actually be marketed at scale to improve elements of the manufacturing, methods of use, all of the characteristics, with an aim of course to having a scalable pharmaceutical product and one that can be protected from an intellectual property standpoint.
That includes things like using a more advanced formulation. LSD is a particularly unstable molecule when it's formulated into a drug product. For instance, our phase II product had to be refrigerated and distributed with cold chain. Logistics around it, obviously something that would be a huge limitation at scale. We've solved for that with an orally dissolving tablet, a Zydis ODT formulation, that we'll be taking into phase III and would look to be the commercial formulation for MM120. Another benefit there is a differentiated PK profile, one where we get faster absorption, faster time to onset of the activity, and also an increase in the overall AUC.
So the time patients are spending in a clinical setting under observation, it can be sort of maximally used, so we have the best efficiency we've seen to date with getting drug to levels in the blood and in the brain that we believe correlate with the clinical activity, keeping them there for longer than the most historical formulations, and then, as a result, trying to sort of maximize the benefit we're obtaining from a limited time in the clinic. So that's, you know, been our overall orientation is to develop innovative improvements to LSD at every stage of the process, and come up with a product that we can take into pivotal trials and ultimately to a commercial scale.
Can you talk a little bit more about just the strategy of pursuing an indication with GAD? You know, a lot of the other compounds are, most of them are being developed in depression. So what was it about GAD that made you go first here?
GAD is an indication that has just been so severely overlooked for about 20 years, and really longer than that. For the history of psychiatry, anxiety has been a core focus, perhaps even more prominent than depression until we had the advent of the SRIs. The last approval, for instance, in GAD, was in 2007, the initial approval in 2004 with Cymbalta. So we've had about 20 years with no real innovation, and that's a large part because it's a very difficult disorder to treat. It's thought of as a sort of constitutive disorder in psychiatry, such that it is not as transient as depression can be. Obviously not to minimize the impact of depression, but depression, by definition, is episodic.
Patients have to go through periods of depressive episode and then have to emerge from that in order to meet the definition of MDD. Obviously, those episodes can be quite long, but generalized anxiety disorder is a lifelong chronic condition and one that has been targeted many times, even since 2004, but has largely been resistant to progress. A lot of the programs that have pursued indications in GAD have not been successful. So we saw it as an important opportunity and also given the historical evidence with LSD in the academic literature, there seemed to be real promise in both treating the sort of mood symptoms, but also treating at some of the sort of a layer beneath that and having these long-term improvements.
The approach has been to focus in an area where many, many different programs have tried and failed. You know, so far, we've been fortunate to continue demonstrating strong clinical evidence that we're uniquely able to see these very rapid and durable effects after just a single treatment with MM120.
Can you talk a little bit more about the GAD treatment paradigm and where you see MM120 fitting in?
Yeah. So current standard of care dominated by SRIs and benzodiazepines. Benzos have largely fallen out of practice, and there's obviously benzodiazepines, SRIs, one of the in the treatment of GAD. Benzodiazepines acutely have their mood and overall effects. Patient anxiety can actually, the current standards of care are really inadequate for the large need. About 10% of the U.S. population present with GAD symptoms, and so our hope and our opportunity here is to provide an acute treatment that has rapid and durable effects, which is a characteristic that is unmatched by anything currently approved for GAD.
Right. That, that's helpful. And then, maybe you can talk more about the clinical data generated to date in the MM120 program, specifically the phase II data and the reasons to believe in this program.
Absolutely. So, MM120 phase II study is really the first comprehensive dose-response, dose optimization study in our field. So we conducted a 200-patient, 5-arm study, where we tested 4 different doses of MM120 versus placebo. That placebo is especially important for contextualization of safety findings, but also because it gives us the most robust ability to test not only our, what we believe are now our active drug levels, but also to characterize things like expectancy bias and functional unblinding in the study, and have really the strongest evidence we've seen to date to support the robust activity of MM120.
We saw a clear, statistically significant, clinically meaningful, and readily apparent dose-response across the dose range we tested, which went down from 25 micrograms of MM120, which is right at the threshold for perceptual activity, all the way up to 200 micrograms, which was double what we expected, a clinically active dose. So this is a full dose range, and we saw a clear dose-response. Importantly, and there's been a lot of conversation in our field about functional unblinding and expectancy, one of the things that is quite interesting from our study is that effectively all of the patients, 85% or greater across all of the four active treatment arms, actively guessed they were on drug.
However, only the two highest dose groups had a response, which of course, cannot be explained by functional unblinding given that response pattern. We saw a 21-point improvement from baseline in our 100 microgram dose group that was durable out to 12 weeks post a single treatment, and the effects were emerged, the positive clinical effects emerged within 24 hours, which is measured by the CGI-S. So we're seeing again this rapid and durable response. The effect size is about double the standard of care, so we had a large placebo response by historical standards of about 14 points, but still exceeded that by over 7 points on the Hamilton Anxiety Scale, which is something we've never seen before in anxiety treatment.
Yeah, that's interesting. So what are the next steps for the program? When are the next catalysts expected, and your expectations around those?
Yeah, so we've guided into phase II in this quarter, which we're very much excited about. From there, we'll be rapidly moving to launch our phase III program. I anticipate two phase III studies to support the NDA. We've been able to operationalize those studies very well and very efficiently in the past. We were in our 200-patient study and enrolled the study in just over 12 months from start to finish. So, we're thinking of phase III studies that are not that different in scale based on the large effect sizes we've seen, and expect to be up and running with those by the end of this year.
Right. Terrific. Maybe we'll go to MM-402. This is another program in the pipeline that I think is starting to get some more interest from investors. So maybe you can talk about MM-402, what makes it a potentially, you know, differentiated compound, and what's the status of this program?
Yeah. So, so fundamentally, as I mentioned before, you know, the analogy we like to draw is how psychostimulants are, which are amphetamines, as the A in MDMA is amphetamine. So the analogy I like to draw is how psychostimulants are used in ADHD, so regularly administered to patients who have an attention deficit and then are able to focus and pay attention, and in a better way. Over time, they can have a sort of trajectory modifying effect because patients then become better self-actualized and have better academic and professional success when they're successfully treated. The goal with our program in autism spectrum disorder is somewhat similar. So we're taking patients who have autism.
The core deficit in autism spectrum disorder is social communication skills, so these individuals have a hard time engaging and sort of fundamentally a hard time seeing emotions in others and engaging with that and communicating as a result of that. So the approach with MM-402 is to try to target those very core symptoms of autism by using a drug that directly kind of improves the social communication skills. We know a lot about racemic MDMA. It's been studied extensively, and the R enantiomer has less of a dopaminergic effect than the S enantiomer. And so what we see with R MDMA is a sort of a less significant perceptual alteration, while maintenance of the sort of prosocial interpersonal engagement.
So again, the exact pharmacology of the drug, the functional pharmacology of the drug seems aligned with the deficit in autism, which gives us an entirely different approach. Again, it's something that is not intended to be a single treatment with a long-term disease-modifying effect, but rather a regularly administered product at an appropriate dose level that would just improve social communication skills in this population.
Right. Interesting. Well, I think maybe with the last few minutes, if we could, we'd like to ask a few questions about the MDMA-assisted psychotherapy Advisory Committee. So this was the Psychopharmacologic Drugs Advisory Committee that met on June 4th was discussing MDMA-assisted psychotherapy, and I think you've already alluded to it, that MM120 is quite different just in terms of not being administered with psychotherapy. So I'd like to touch on a few aspects of this advisory committee, but I think first, maybe, can you just talk about how MDMA-assisted psychotherapy, you know, how it differs from your lead programs?
Absolutely. So I think one of the most obvious sort of headline differences is exactly the dash AT, right? So the, in the briefing documents, and the entire discussion was around MDMA-AT, and the dash AT stands for dash Assisted Therapy. As I said, you know, at the outset to today, core to our approach, core to our development programs, has been to eliminate that entirely, and that is with a mind to maximize access and scale so the patients can actually access the products, and also avoid some of the methodological concerns that assisted therapy or using two interventions at once would introduce to a development program. So, you know, as we looked at the AdCom and the outcomes, obviously, the vote was quite negative.
I think below that, there was a lot positive, and there was encouraging support for MDMA as a potential therapy. There's support for psychedelics and the promise that they may hold in the treatment of psychiatric disorders from the same advisory committee who voted against that specific application. One of the biggest challenges that we heard voiced was the complexity introduced by using assisted therapy, using a psychotherapeutic intervention, effectively talk therapy, in addition to the drug, something that, again, we have, you know, avoided and gone entirely the other direction from day one in our program.
Some of the other specific items that were raised that, you know, are easy to address, you know, we capture adverse events robustly, as you would in any other clinical development program. We'll have a full cardiovascular characterization through our development program. You know, we have absolutely no concerns that there was any relevance from any of the specific commentary or issues that were raised during the AdCom to our program. Similarly, because again, from day one, we have built this and developed our products like you would develop any other drug in psychiatry, irrespective of what drug class comes from. That's core to our DNA and core to the people that we've brought into the organization.
The one, you know, broadly applicable methodological issue that was raised was functional unblinding, and that's something that I think uniquely has been focused on in our field because of the different qualitative nature. It is not unique to psychedelics. I mean, functional unblinding is par for the course for every drug in psychiatry. It doesn't. You don't have to look very far, you know, Spravato has ketamine, and GAD, Xanax, right? Benzodiazepines have really significant acute effects on patients. And so, this is something that we are mindful of, that we go to great lengths to mitigate, both for the participants in the study, for the sites, but also most importantly, for the adjudication of the outcomes that we're assessing, right?
So we use central raters blinded to treatment assignment and visit number, and we've actually presented data now showing that 80% or more of the raters couldn't guess what treatment a patient was on, regardless of when or where it was in the study. And even when they did guess, they were often quite wrong, and the patterns were consistent across the dose group. So, we're very confident in the integrity of the blind and the integrity of the rating and the scales that we had achieved. But, you know, in terms of patients feeling the effects of the drug, the reality is that drugs that affect one's brain, people can feel the effects of.
It seems quite obvious when we kind of zoom out, but it's very easy to get, you know, just spun up about methodological concerns and trials. We'll continue to go to lengths to try to mitigate this to the greatest extent possible. But again, given the large, durable effects that we're seeing after just a single treatment, I think that's not something that would be a barrier. And, you know, I'd just also point to anyone who watched the AdCom; I think has observed and commented on the fact that it wasn't any one particular issue that was raised that led to the outcome of that vote, but rather a sort of constellation of various concerns that were raised that added up to an ultimate outcome for that AdCom.
So, we're really excited about, you know, the ultimate carry-through to us and what it means, which is that, if we do a appropriate development program and are robust in our approach as we have been and will continue to be, we think there's a lot of support across the board for these types of programs.
Right. Terrific. Well, I think we're gonna have to leave the discussion there, but always helpful, always interesting to hear the update of what's happening at Mind Medicine. So congrats on all the progress in the pipeline, and with MM120, we're really looking forward to the start of that phase III program. So thanks to Rob Barrow and Mind Medicine for attending the conference, and thanks for everyone, you know, all of our attendees for being with us, and have a great rest of your day, and have a great rest of your conference.
Thanks, Patrick.