Yeah, yeah, yeah. All right, we're going to get started. Thanks, everybody, for joining us. There you go. Come on in. We have MindMed next, Rob Barrow, who is the CEO. Thanks again for joining us. This has been one of those very interesting stories in the psychedelic space. There are so many companies that are trying, right, in the psychedelic space. What was interesting about your story from the very beginning is you were doing things just a tad different. There were not a lot of people doing LSD. It seems like everybody was doing psilocybin. You know your lead program is anxiety. Everybody else's lead program was something, you know. I always felt like, wow, okay, this is really differentiated. You look at the data, and you are like, holy cow, this really works.
Now we've got to figure out a way to get this forward to the market. That was kind of my quick takeaway. Tell us about how the company came together. Tell us about where your product, the technology, kind of came together. Just give us a quick kind of update to where the study was. Then we'll want to talk about the data.
Yeah, yeah. Kind of going back in time, definitely an evolution of the company in the first iteration, predating our current management team, myself, leading into 2020, 2021 time frame. Since then, we really turned around the entire company, board to every employee, and have built it from the ground up over the last four or five years. It has been a really rewarding journey. Obviously, LSD is not a drug that we discovered. It has been around for about 100 years. It is one that we have continued to improve upon and certainly had a lot of regulatory and clinical progress to date. Over the last year, you mentioned about 12 months ago, almost exactly right before the 2024 conference, had phase II data, got a breakthrough designation for our lead program, LSD and generalized anxiety disorder.
Since then, have continued to build out the team, brought in a really incredible leadership across the board. Now going into a year of execution, but three phase III readouts in 2026. that are really excited about one step closer to market.
Just explain to people exactly what it is. I mean, everybody understands LSD, but what exactly are we talking about? What are the patients taking, and how was it made, or where was it found?
Yeah, so LSD, our name for it is MM-120. It's an orally dissolving tablet, same as we've been talking about Nurtec ODTs a little bit before this. Same technology out of Catalent. Some advantages there, the ultra-rapid dissolution, which leads to faster absorption, faster onset of drug effects, and a differentiated clinical and physiochemical profile. Took the old molecule, optimized the performance clinically, and landed on the ODT formulation, which we then conducted a bridging study last year and now have in the phase III program.
okay, so let's talk about the phase II. Tell me about the program and what the data was.
If we go back in time a little bit, this reemergence of research with psychedelics really started out of academia. And primarily at that time around psilocybin, a sort of fascinating conversation I got to have early on in the field maybe seven years ago was talking to some of these early researchers saying, why psilocybin? Is there something about it? The comment that I generally got back was, well, I didn't think my department chair would let me study LSD. It's a drug with a long history. It obviously was a catalyst for the Controlled Substances Act and really put on ice for the better part of 30 or 40 years. That unfolded. At the same time, over in Switzerland, there's a lot of research happening with LSD and MDMA and many of the drugs in this class.
We looked at the data with LSD, and it really stands out for both the magnitude and the durability of the response that we've observed. Going into phase II, we certainly had a lot of information about the general performance. Obviously, it's a well-known drug. How it loosely behaves has been talked about a lot and been studied a lot. One of the things that had been really overlooked in our field and in the historical literature was just actual clinical performance in modern diagnostic areas in depression and anxiety. Really poor characterization of dose response, for instance. A lot of assumptions being made. There's also a legacy of these drugs being studied in the context of a drug plus psychotherapy model. The reemergence of research really embraced that, for not particularly scientific reasons, but just out of tradition.
As we conceived of the program, we wanted to make many of those decisions that were quite distinct from the rest of the field, going after the broadest possible indications. We want to be able to actually have a meaningful impact. These are some of the biggest indications in medicine, certainly in psychiatry, upwards of 50 million people who suffer from anxiety and depressive symptoms. We wanted to have a label that would be as broad as possible and lead to the broadest ability for adoption. The other thing we wanted to do is demonstrate that the drug actually has an effect on its own, that without a psychotherapy overlay, the drug can actually perform, because that's the sort of bounds of what FDA regulates. We also thought that a lot of the scientific questions had not been adequately answered.
Dose response dimension mentioned, there's a lot of methodological intrigue around how to study a drug that has such distinct, clear functional effects like LSD. We did a five-arm phase 2 study looking at a complete dose response, including a placebo, doses of 25, 50, 100, and 200 micrograms. As a result of that study, what we saw is that the 200 patients study in total, we saw that a clear dose response that was both clinically observable and statistically significant, we saw that after a single dose, the two highest doses, 100 and 200 micrograms, led to a 12-week durable effect that was present as early as it could be measured. Depending on the instrument, as early as the day after treatment, that persisted out to 12 weeks. We just stopped following patients. Didn't see any degradation of that response v ery likely could persist much longer. We did that in the absence of any psychotherapy. That kind of robust drug effect really establishes that there is a real drug action going on. The other thing we saw by doing the dose response study was a data-driven decision for the dose to take forward, 100 micrograms, and clear evidence that the drug's effects are not simply due to the functional unwinding of the functional effects. What do we mean by that? In the study, virtually everyone who got drugged knew that they were getting drugged. 88% at the lowest dose that we tested, up to 100% at the highest doses we tested, correctly guessed that they had received drug in the study. These were patients who were kept in a room for eight hours.
Most of them who got drugged said, yes, I think I got drugged when asked. What we showed is that the two high-dose groups had this dramatic clinical response. It was from baseline, a 22-point reduction from baseline, which has never been seen before in GAD studies. A placebo-differentiated, so a placebo-adjusted response of 7.7 units 12 weeks after a single dose. Patients come in room one time, and three months later, they've got a 7.7-point improvement over placebo, which is more than double the standard of care. Just data that we have never seen anything like it. Even more remarkable is the fact that half of the people were in remission after that single administration. Yet again, just not data that we've ever seen in disease like generalized anxiety.
So this is this on the MADRS?
On the HAMD and GAD.
This is on the HAMD? You did not measure the MADRS. You measured the HAMD?
We measured the HAM-A and anxiety and then the MADRS for depressive symptoms. There's a high degree of overlap.
I guess I was measuring that up, the HAM-A for this one. What's standard of care right now in anxiety, and what is the average kind of improvement that you see?
Yeah, typically we see a, first of all, standard of care primarily dominated by SRIs, historically benzodiazepines as well, although those have fallen out of clinical favor pretty significantly. Historical studies with SRIs, for instance, and Xanax and the benzos as well, we see about a 14 or so-point improvement from baseline, really around the size of the placebo response we saw in phase II. We see a placebo response of about 10 units. Somewhere between a 3.5-4-point improvement over placebo would be standard. We're seeing more than double that in our program.
When you set out to 12 weeks, how are you confident that it was out to 12 weeks? What were you doing? Basically, patients are not on anything.
Correct.
You're just measuring the HAM-A. At what points were you measuring?
Right, so we dose patients, then we follow them at weeks 1, 2, 4, 8, and 12.
One, two, four, eight, twelve.
You get a pretty granular definition of the treatment response over that time frame. Again, we saw the response as early as the HAM-A can be measured. It's a one-week recall instrument, so you can't measure it validly before one week. At one week, dramatic near-maximal reduction in HAM-A scores. We saw no loss of activity from week 1 out to week 12.
Pretty amazing. What about any side effects, anything that was, I mean, obviously, we know what the side effect of taking LSD is, so to speak. That's not the side effect, though. It's what you're looking for. Anything unusual?
It is certainly an interesting dynamic with any clinical research where we capture even positive or pharmacodynamic effects as adverse events. Effectively, the AE profile was largely limited to dosing day. Things like illusions and hallucinations, I mean, exactly what you would expect when you're on this dose of normal.
LSD, exactly.
To capture that, I think it satisfied FDA that we're doing a good job at capturing adverse events. Beyond what you would expect just from knowing about the properties and the activity of LSD, nothing really to speak of. We see low levels of nausea. Really, again, almost entire AE burden is limited to the day of dosing. Thereafter, we see almost nothing.
okay, let's talk about the phase III trial. Obviously, very excited, high effect size. What was the effect size on this?
It was 0.88.
It was like 0.88, very high. High effect size, everyone's excited, we're moving into phase III. What's the phase III look like? What's the timing? What's going on?
Right, two phase III studies, virtually identical designs as the phase II, with the difference that we're doing one study, Voyage, which is a head-to-head study of 100 micrograms versus placebo. In the second study, Panorama, we have added, in addition to the 100 and placebo doses, a 50 microgram dose level. That's to sort of methodological control to try to basically confuse patients so that if they feel something on the day of dosing, they can't know that it's actually drug. They know that it's something, but it could be a clinically inactive dose. Dose patients one time, follow them for 12 weeks, with the primary endpoint being the HAM-A change at week 12. Another unique feature about the phase III is that we then continue patients on for nine months thereafter.
It's an extension period where they have the opportunity for open label retreatment, up to four doses over the subsequent nine months. That allows us to characterize the sort of dynamics of retreatment, the safety of retreatment, what the average treatment profile looks like. What we see out from the real world is that after an acute phase of treatment, what be at one or two doses, patients generally have a pretty durable response, obviously to be defined more granularly, but that we don't typically see a sort of regular interval of administration, but rather an acute administration that leads to this durable effect, whether that takes one or a couple of days.
Yeah, what are you seeing on the open label so far? Are we out there yet?
Yeah, can't speak to the open label data quite yet. Certainly because of the nature of the study, in most open label extension periods for a daily drug, for instance, once patients roll over, they become unblinded and they're taking open label drugs. The dynamics are here such that once patients continue into the extension phase, they're still in a randomized status until they take an open label drug. They're only eligible to do that if they have a HAM-A score of 16 or greater.
Right, so if it pops back, okay.
If a patient takes a single dose and say it's an active, hopefully, dose of drug at their first administration, and then they just stay in remission for a year, what we'll do is just have observational data over that period. We'll certainly understand for at least that patient or that group of patients that they don't need more than one dose.
How often in this open label time, how often are they coming back in? Or are you calling them? How are we finding out if they need a pick-me-up?
Yeah, we use both the screening tool, the GAD-7, and also the Hamilton Anxiety Scale. The GAD-7 is something that is rolled out in clinical practice today and recommended by the U.S. Preventive Services Task Force based on GAD-7 scores. Regardless of those, monthly, we're testing patients on the Hamilton Anxiety Scale. If they have a 16 or greater, they'll be eligible for readmission.
Do they come in or you're testing them at home?
We do both. Some in-patient visits and some of them are remote.
Right, okay. They were allowed to come back and do four doses plus the one. It would be, theoretically, it would be five over the course of a year.
Up to five over the course of a year.
That would be the most you could, right, right, got it, got it, got it. okay. Enrollment, how are we doing on enrollment?
Yeah, we've been really encouraged, I mean, by the early enrollment. We just dosed our first patient in Voyage in Q4 of last year and first patient in Panorama in January of this year. Both studies, we've just been really seeing an overwhelming response from patients and providers and a lot of enthusiasm engagement to get patients into the study. There is just very, very little out there for GAD, both in practice and in research. What we have heard over and over again, it was two of our clinical sites yesterday. What we hear continuously is that when given the option, patients really want to be in a study where they can take one dose and then perhaps have a durable effect.
With sites that have had multiple GAD studies ongoing, we've seen a pretty heavy skew to selecting patients and putting them in our studies versus others as well.
How many sites do you have in the phase IIIs? How many are overlapped? How many versus the phase II that you had? What was overlapping?
Yeah, so in phase II, we had 20 sites spread throughout the U.S. In Voyage, we have just under 30 sites all in the U.S. In Panorama, we have about 35 sites spread throughout the U.S. and Europe.
Right, and those are different sites versus Voyage?
Correct, at the outset. We had the ability to roll.
How much of those do we have all 20 sites from the phase II within the 65? Were you happy with all of them?
All of the good performing ones, all the ones who did a good job in rolling and screening patients.
We left a few out.
We chose to go forward with the ones that were.
How are we making sure that these are actually patients who are real anxious patients?
We go through extensive screening, including a diagnostic tool, the many multiple Hamilton anxiety assessments conducted by a central rater that's not only blinded to eventual treatment assignment, but it's blinded even to visit number or where a patient is in the progression of the study. We also use a third-party interview called the SAFER to confirm independently that the diagnosis is real. About as extensive as one could possibly go to ensure we're getting real patients.
Yeah, that's pretty, I mean, that's the biggest deal here, right, is the placebo effect. Can we eliminate the placebo? In this situation, you would think, right? I mean.
One of the things in.
It would be pretty dramatic, you kind of know.
Yeah, one of the things in phase II that was actually so encouraging to us and really unique in our field is that we saw a dramatic placebo response. I mean, most anxiety studies see a placebo response of about 10 points on the Hamilton Anxiety Rating Scale. We saw 14 points from baseline.
Yeah, that is true.
It's about as good as you see for benzos or SRIs. We still beat it by almost eight points. That really speaks to the robustness here, because when we see programs where there is no study where there's any sort of placebo effect, it really calls into question whether the drug effect is real or not, right? Whether you're just seeing this functional blinding leading to a nocebo response. We've been really fortunate to have such strong data in phase II.
okay, so we've got these two studies ongoing. What else do we have ongoing with the product?
A phase III study that was starting the first half of this year called Emerge, that's a major depressive disorder, virtually identical design with the caveat that, like all depression studies generally, we're using the MADRS at week six as the primary endpoint as opposed to the HAM-A at week 12. Virtually all of the sites are overlapping with the anxiety program, which has great operational efficiencies. Effectively, in anxiety studies, if a patient is in a major depressive episode, we exclude them. At sites where they exclude someone who's in a depressive episode, they instead of being put on Voyage or Panorama, can be put right on to Emerge. We maintain those patients and effectively don't have to let them go. We can include them all one study or the other.
It really helps with operational efficiency, both how we set up the sites and monitor them, but also how we maximize the efficiency of patient throughput.
30 or so sites here, what are we talking about?
Slightly less, yeah, around 20 sites.
Twenty-six sites, fine. In this situation, we do not have like a true phase II proof of concept study. This is more of a, this should work, let's do this too, kind of thing.
In major depressive disorders specifically, there has been some academic work using some different endpoints that have been encouraging. What we saw, there's an important distinction here, which is that obviously with anxiety and depression, they're both diagnostically highly comorbid. From a construct standpoint, both the scales and the diagnoses are highly overlapping as well. What are we about? Around 60% of patients who have GAD or MDD have the other disorder as well. Even the symptoms, I mean, item six on the Hamilton Anxiety Rating Scale is depressed mood. The scales we use and the diagnostic criteria are so significantly overlapping that it's pretty easy for a patient to have both disorders. We did also observe a dramatic and durable effect on the MADRS in the GAD population. Now, they weren't in a major depressive episode.
Just by the disease definitions and the scales we used, we saw they had elevated depressive symptoms. We have some preliminary data, but we do not have the standard sort of proof of concept given the long legacy of potential immune anxiety disorders of the class.
You've built in an interim to the anxiety, going back to the anxiety, right? Both anxieties have interims.
Correct.
Just talk about the strategy there and the timing and what would be scenarios.
Yeah, so effectively in both studies, the arms of interest, the ones that we're testing statistically, are the 100 microgram and the placebo groups, both of which have 100 patients at the outset. We do halfway through the study when half the patients have completed 12 weeks, we do a blinded sample size re-estimation. We've made assumptions around the standard deviation of the data and around the dropout rate. If either of those are larger than we anticipate, then the blinded re-estimation will allow us to increase the sample size by up to 50% so we don't lose power. Now, these are almost an eight-point improvement in phase II. We're at 90% power in both studies to detect a five-point difference. So pretty good margins there.
Just to make sure, an abundance of caution to make sure we don't lose power because of non-directional variance or just because patients drop out from the study, we can increase the size up to 150 patients in each of the arms of interest.
Interesting, okay. The timing of that is sometime next year, this year?
We haven't given exact guidance on when the timing of the re-estimation would occur, but it would be when about half the patients are through 12 weeks through the primary endpoint.
There has been no guidance with respect to how long you expect this trial, when the data is coming, or what are you even telling people?
Yeah, for Voyage, first half of 2026, and for both Panorama and Emerge, second half of 2026.
okay. Let's talk about the commercial model. I think we have to start with Spravato. Explain to everybody what Spravato has done, what did J&J do well, and how will you be able to leverage learnings from J&J?
Yeah, so Spravato, intranasal esketamine, it's now been about five years or so since it's been on the market, six years since it's been on the market, with a label for treatment-resistant depression as an adjunctive therapy and just recently as a monotherapy in treatment-resistant depression. To date, about 60,000 patients have been treated according to J&J's filings.
60.
$60,000, and now running at $1 billion a year. Obviously a not insignificant revenue driver for a drug that is quite burdensome for delivery. Spravato, it's a dissociative. Ketamine, of course, is a dissociative anesthetic. There are some early observations that the mechanism seemed to have an antidepressant effect. Spravato is administered twice a week for the first month in an induction phase and then once weekly thereafter. Each administration, it's a two-hour monitoring period that's required for a total of up to 56 doses a year. A lot of time patients are spending in the clinic getting delivered the drug. There are roughly 4,500 clinics certified under the Spravato realms to deliver it. We see a pretty concentrated, about 800 or so providers are responsible for, excuse me, 600 or so providers are responsible for 80% of the scripts for Spravato.
A really concentrated set of interventional psychiatry clinics that are now delivering Spravato at a pretty significant scale. Those centers are highly motivated, and our research with them very engaged in preparing for the delivery of psychedelics, of drugs like MM-120, should it become approved. In order of magnitude, there's something like 75% of those providers say, delivering your drug would be more economically attractive to us, would be easier for us to administer. Of course, the way our drug is delivered, it's a longer single day of administration. Something like eight hours is what we're requiring for monitoring in the phase 3 program. So far, what we're seeing is such a durable effect that instead of coming back twice a week, patients may only need to come back never.
Even if it's once a quarter.
Once a quarter, right? That's certainly what we would expect to be there or even better. Those dynamics have been really encouraging for both patients and providers. The economics for delivery, both at the site level and from a market access reimbursement standpoint, are incredibly attractive. We are really launching into an infrastructure that has been built out because of the adoption of both racemic ketamine and Spravato. It is very much the low-hanging fruit, clinics that are ready-made to deliver our drug.
How do the sites make money?
Two delivery models. One is buy and bill. They're buying drug, and they're making a significant profit based on selling that drug to patients. The other is being reimbursed primarily for monitoring time. It is relatively attractive economics for monitoring multiple patients who are getting Spravato at a clinic at a time, something around the order of $150 an hour to monitor these sessions. Both economic models are viable for these sites. It turns out Spravato and much of the research we've done is really a profit driver for many of these clinics, is really profitable and something they're excited about.
Interesting. Do they use ketamine for anxiety as well? I mean, Spravato's not approved for it, but I guess it's so close, anxiety.
There has been, yeah, there's certainly been a lot of cross-diagnostic use. We see this in psychiatry all the time, right? That mood and anxiety disorders are so significantly overlapping that very often drugs are used off-label. Certainly, drugs labeled for MDD are used in GAD quite frequently. The predominant use for Spravato certainly is in treatment-resistant depression.
Let's fast forward, your product's on the market. Help us think about, you don't want to talk about pricing, but just frame some type of reference for us to think about pricing relative to, talk about the Spravato pricing, I guess we can.
Yeah, yeah, I mean, I think it's a great analog to look to because of, again, some more burdensome delivery dynamics for Spravato would appear based on our research. Even there, Spravato, dependent on the dose and the frequency with which patients are taking the drug, can cost anywhere between $25,000 and $60,000 a year just for the drug as a pharmacy benefit. In addition to that, the medical benefit, which is paying for the monitoring period, 112 hours a year. That can add north of $15,000 or $16,000 a year of cost for payers. When we look at a dynamic where drug can be taken much less frequently, certainly the pricing and the health economics are such that there's an incredible value capture. I mean, GAD is a diagnosis that for the long history of psychiatry was a real prominent focus.
With the introduction of SRIs, the diagnostic drift towards depression was quite significant. There is this huge burden of moderate and severe GAD, both in diagnosed patients and in undiagnosed patients or patients who have an MDD but not GAD diagnosis. Demonstrating the burden both directly on health care utilization, but also on things like productivity and the workplace, on absentee and presenteeism, is really quite staggering and is linked to severity. There is a really compelling value argument within any sort of reasonable pricing.
Is it fair to say 25-60 is a fair range for how you price your product per year?
Yeah, certainly a little premature to say precisely. As we look out into the market and look at other drugs, including other new entrants in MDD that are not nearly as significant leaps forward in terms of patient outcomes, there's a really attractive argument to be made that we think will lead to really attractive pricing.
Yeah, I mean, that's obviously very attractive pricing. There is another product that you've talked about, and we haven't really done a lot of research on this yet, but you're in phase I, MM-402. You want to talk about this product a little bit?
Absolutely. It is the R-enantiomer of MDMA. MDMA is a drug that was being studied for post-traumatic stress disorder in a similar sort of session-based delivery. Our approach with 402, with our MDMA, is to really look at the direct pharmacology of the drug. What does that mean? We are studying in autism spectrum disorder. We have a good understanding of the pharmacodynamic profile and sort of behavioral profile of patients who take MDMA or our MDMA, and we were able to define in phase I as well in healthy volunteers. The core symptoms of autism spectrum disorder are social communication deficits. It happens that the direct activity of MDMA and our MDMA is to be prosocial, to sort of facilitate interpersonal connectedness and ability to basically communicate.
The goal there is to identify a dose and a regimen that would, simply, the analogy we like to draw is how psychostimulants work in ADHD. That it's not about changing or treating, fixing the disorder of ADHD with a psychostimulant. It's that while the drug is on board, while it's having its activity, individuals are better able to focus and function. That is the goal of the MM-402 program in autism spectrum disorder and something we're excited to eventually move into patient population.
I think everybody understands what MDMA is, right? That's ecstasy. Like you said, that's the drug that Lykos had trouble with getting through FDA for a whole bunch of reasons that we do not need to backtrack again. But our MDMA, why that isomer?
Yeah, it's a great question. It's primarily serotonergic isomer of MDMA. We see a much more dopaminergic activity, much more of the sort of amphetamine-like properties of MDMA are associated with the S-enantiomer . Some of the preclinical work and certainly now some of the human clinical work that both we have done and others have done have pointed us in the direction that we're seeing a profile that would be more aligned with perhaps a reduced AE burden compared to the S-enantiomer and maintaining or even enhancing those prosocial effects.
Interesting. So it's more dopaminergic than the racemic?
It's less dopaminergic.
Less dopaminergic. You said it's less dopaminergic.
More serotonin.
It's more serotonin, is what you said. Yeah, yeah. Interesting. I didn't know that. And the AEs are less? Like what AEs are you referring to?
Many of the stimulant-like properties, right? Increased heart rate, blood pressure, temperature, things of that nature.
Interesting. okay. Last question is IP on both of these assets.
Yep. I mean, we've got a robust patent portfolio. Last year, we got a pretty key patent on our MM-120 ODT formulation issued. It's an Orange Book patent that we're really excited to have in hand. We've solved not only for some direct benefits there that would block out any sort of generic entrants, but also clinical performance advantages, getting drug into the system and to a level of therapeutic effect faster compared to any other formulations that we've studied, and also leading to more time at those therapeutic concentrations. We get a better AUC without any Cmax change, which means harder to replicate PK profile. It means beyond just the patents have been granted a nice mechanism for protection later on.
Oh, interesting. Excellent. Thank you. Thanks for joining us.
Thank you.
Good luck with everything.
Appreciate it.
All right.