Biotech analyst for Cantor, some would say the most senior biotech analyst at Cantor, and it's a pleasure to introduce the next presenting company, which is a company called MindMed. And, MindMed is a company that is developing an innovative, class of drugs for the treatment of common psychiatric disorders. And, I've known this company for several years, and so it's really great to speak to this company. I do cover it. We do rate it with an overweight rating, and it's a pleasure to introduce Mr. Rob Barrow, the company's CEO. Rob, thank you for joining us.
Thanks so much for having us.
Good to see you.
Yeah.
All the way in from Madison, Wisconsin, which is increasingly a cold place, but a place dear to my heart. MindMed is a company developing a psychedelic, and, you know, you'd have to live under a rock to not have any perspective on whether or not those agents could help to treat psychiatric disorders. Rob, why don't you tell us a little bit about yourself, and why you came to MindMed, and why you're interested in this space?
Yeah. It's an incredibly exciting one. I think when we look at the landscape of healthcare and disease burden, obviously, you know, even in common press, the mental health epidemic we have in this country and really around the world is quite staggering, and we've had so little meaningful innovation in the last two or three decades even, especially in anxiety, which is an area of focus for us. So, pharmacologist by background, and I've had the fortunate opportunity of being involved not only here at MindMed, but with a few other companies historically in this exciting, you know, renaissance of psychedelic research.
I came to MindMed at the beginning of 2021 to really build out a team, and you know, some of the legacy approaches and legacy studies in this area have been, I think, less informed by data and more informed by the historical practices and just you know, precedent and tradition, if you will. So we decided to take an approach that was what you would expect of any drug company, you know, designing studies to try to answer some of the really difficult questions that face us in CNS research broadly, but particularly with this drug class. We earlier this year put out data for our lead asset, MM120, which is a proprietary form of LSD that's in development for generalized anxiety disorder and for major depressive disorder.
Obviously, we put out phase II data in March of this year, received a breakthrough therapy designation, and what we saw in those data, and what gets us, and I think the entire, certainly, psychiatric community excited about the potential here, is that with a single intervention and no additional therapy, nothing beyond giving a patient a drug and watching them in a room for a day, we saw a dramatic, you know, clinical response. An effect size was about double that of the standard of care, and a durable response that showed reduced anxiety and depressive symptoms out to twelve weeks with 50%. One in two people who walked into the room in that study came away in clinical remission. These are numbers we've...
You know, unlike anything we've seen in psychiatric research in quite a while, and so, it gives us incredibly excited to embark on a phase III program now in both of those indications.
Yeah, there's been a lot of questions recently about the development of psychedelic drugs, if you will, but also really should be more broadly central nervous system-acting drugs generally, about whether or not patients know they're on the drug or investigators know they're on the drug-
Mm
... and if that can confound the results. So, you just stole one of my good questions, which was, what are you most proud of having accomplished? But let me still ask that question of the last year: What was it about the phase II data that you want to highlight, that really start to address some of these potential confounders?
Yeah, the top level, the thing we are most excited about is that magnitude of benefit for patients. And in GAD, the last approved drug was Cymbalta. It was initially approved in 2004. That's 20 years without a new drug approval, and an indication that is has a prevalence of about 10% of U.S. adults. That's 20-plus million people. But digging a layer deeper and with some of the methodological concerns and challenges that we face in CNS development, there's been a particular focus in our field, the attribution of clinical effects and the potential confounding of functional unblinding, we call it.
Yeah
... right? The fact that people take LSD, they take MM120, and they feel the effects of the drug. Now, our view is that that shouldn't be a surprise because that's how all psych drugs work. I mean, people take two milligrams of Xanax, and they feel the effects of Xanax, and it turns out that the sedating effects of Xanax are why it reduces people's anxiety. The same is true for virtually every drug class we have in this area, but, you know, a spotlight has been shone on our field because of the unique qualitative nature. Obviously, taking LSD feels quite different than taking Xanax or other CNS drugs. What we did, though, in phase II was try to address this, try to understand-
Mm-hmm
... if we can see a drug effect independent of that. So we did a really most expansive dose response study ever conducted with this drug class. And-
For any of these drugs.
For any of the drugs at any time-
Yeah
... in history, and so really, for the first time, we got a real clear insight ... about the attribution of functional unblinding to the treatment effect. We saw, we tested four active doses of drug versus a placebo-
Mm-hmm
- from a dose level of 25 micrograms, all the way up to a dose of 200 micrograms. And for reference, our go-forward dose in phase 3 is a 100-microgram dose.
Yeah.
It turns out to be the sort of peak clinical effect. What we observed is that 85% of patients across all of the active dose arms, from 10, 25 milligrams on up, correctly guessed they were on drug.
Yep.
They knew they were getting the drug.
Yeah.
But as it turned out, only the two high doses, 100 and 200 microgram dose levels, showed a clinical response. The lower dose groups were virtually identical to a placebo response. That can't be the case if functional unblinding.
Right
... is causing the clinical effect, which is something that got us, you know, even more excited about the integrity of these data and the understanding of the mechanisms at play here, and as we went into our end-of-phase-two meeting, also gave us a really nice opportunity with the agency to have a constructive dialogue about answering this question, and about a clean design as we embark on the phase three program.
And interestingly, the investigators knew that those patients were on the drug as well, or could guess, could have guessed. And so probably, that dose response probably says something about, you know, call it expectation bias, and the investigators read what the patients were experiencing.
So presumably, the people in the room, who we call dosing session monitors, right?
Yeah.
These are patients who FDA requires us to have under observation for the day of their treatment. Presumably had a decent chance of guessing what patients got as well. They had no involvement in actually rating the symptoms-
Sure
... on the Hamilton Anxiety Scale, and anxiety on the MADRS and depression.
They were blinded, right? Blinded raters.
We use central raters, right?
Central.
We use central raters blinded both to treatment allocation and visit number, and we found that 80% of the time, those raters were unable to guess. They said they didn't know what they thought a patient received.
Okay.
When they did guess, they were wrong.
Excellent. Good, so those two, you know, call it observations, give you confidence that what you saw was not hope. That, "Wow, I'm going into a trial. I'm gonna take LSD, and I'm gonna feel better. I'm gonna feel less anxious," correct? Does that hit the mark with regard to what the FDA wants to see, and how have you used those observations to design your next step?
Coming out of our end-of-phase-two meeting is exactly those data we tried to. You know, we did present to the agency to try to come away with as clean of a phase three design as possible. We try to answer all the questions we possibly can in phase two, so that we can have a straightforward and easily interpretable phase three program. We certainly feel and came away from our end-of-phase-two meeting feeling that we've reached that consensus, and that in so doing, we now have two phase threes, one of which is just a head-to-head study of MM120 versus placebo, and the second which we have effectively the same design.
The two doses of interest that we're statistically testing are 100 micrograms versus placebo, but we've also added another control, a lower dose group.
Lower dose
... to try to confuse people, to try to have them-
Mm-hmm
... not be able to guess whether just feeling the effects of a drug would be enough to drive some sort of clinical response.
So two different studies. One's called Voyage. I love it. And Panorama. Soon to start. When do you think you can first operationalize the first one?
So we've guided the first study will be starting before the end of the year. Our team has done just an exceptional job of getting these studies up and running, so always looking to accelerate our timelines, and we've been, you know, incredibly proud of our clinical group for how fast and effectively, and really the whole organization. These are complex studies to design, complex studies to run, and, you know, we've been able to really exceed in that avenue. So, have three phase 3 readouts now coming in 2026, that we're really excited about.
Including MDD being the third?
Correct.
Okay. So you just said 2026. So what gives you confidence that you can enroll these studies? They're not small. 200 patients in Voyage, or so. What gives you confidence that you can enroll them within that time period? And the endpoint is a 12-week endpoint, right?
Correct.
Is that necessary and sufficient for an NDA filing?
We certainly believe it is, yeah. All depression and anxiety drugs have been approved on endpoints shorter than 12 weeks.
Yep.
Or I should say 12 weeks or shorter.
Mm-hmm.
And so we've yet to see any drugs require a longer durability, and certainly when we're talking about a single intervention, you run into just complexities of keeping patients enrolled in studies if you go much, much further than that. So we've had alignment with the agency that a 12-week endpoint is appropriate for a phase three program, and, you know, in GAD, and then in MDD, we'll be using the more traditional six-week endpoint for depression.
Sure, yeah. Let's talk a little bit about Voyage. It's a U.S.-only study, correct?
Correct.
It's a 200-patient study, two arms.
Right.
So really reduce the expectation bias in terms of, say, patients-
Yes
... hoping they're on the drug because they are randomized to, you know, a bigger arm or whatever. One-to-one randomization.
Correct.
12-week endpoint, and then what happens? Open-label extension?
... So it's been, for shorthand, talked about as an open-label extension at times, but really what it is is an extension study. So we have patients for 12 weeks-
Not, not open label?
It's an extension study for nine more months, during which patients will have an opportunity for open-label treatment.
I see.
That's really an important, important aspect because until a patient actually receives open-label drug, they're still in a blinded status.
I see. Interesting.
So as we go out beyond 12 weeks even-
Ah, okay
... we haven't recruited anyone-
Right
... in random label capacity.
Right.
We can look at things like Kaplan-Meier curves and survival-
Sure. Durability
... durability even beyond-
Yeah
... 12 weeks and start to understand-
Mm-hmm
... What is the average time it takes for a patient to actually need a retreatment with this drug?
Yeah, yeah. That'll be interesting data, and then whether or not a patient's interested in signing up again and how many, up to four additional doses?
Correct.
That's, that's the case. What, what do you hope? After three months, you're gonna have primary endpoint. What would you like to see out of the treatment arm?
Well-
What would the agency like to see?
Certainly what we... You know, the bar for GAD is not particularly high.
Yeah.
SRIs, SNRIs, generally have effect sizes less than 0.4, a Cohen's d of 0.4-
Sure
... which corresponds to about a three-to-four-point improvement over placebo.
Not, not very strong.
Not particularly large. So, we have certainly been conservative in assuming that we're going to have that sort of magnitude of response over placebo. Even still, we have more than adequate power, and-
Sure
... if we can replicate both the magnitude of the response and the durability that we saw in phase two, you know, that would be extraordinarily exciting just because it is so remarkably different than any available treatment options today. And it is, you know, so much more durable and so much more impactful for these patients. To actually start having conversations about getting patients into remission in a sizable number of patients into remission, at the end of the day, that's what people generally want is to feel better, not just to have-
Yeah
... their symptoms blunted a little bit, which is what, you know, characterizes the current standard of care. So if we're able to get anywhere close to replicating what we saw in phase two, that would be, you know, I think exceed anyone's, you know, wildest expectations for what a drug can do in neurotic illness.
So it'll be effect size and then maybe a response rate and then a remission rate and then perhaps a durability.
The way we've constructed the endpoints, it will be a 12-week primary endpoint, and then we want to show rapidity-
Yeah
... of response, or we want to show that-
Mm-hmm
... as early as we can measure the HAM-A at week one, that we're seeing an effect-
Sure
... ideally, and then, then we want to look at durability as well, durability beyond, and that's where we use the Kaplan-Meier and survival analysis to look at the average time until patients, you know, don't, don't either achieve efficacy, have inefficacy, or, or need retreatment.
What happened in the first phase two in terms of rapidity of response? Wasn't it pretty fast?
The first time we measure it is the morning after a treatment session, and we saw a statistically significant and dramatic reduction. We have to use the Clinical Global Impressions - Severity Scale because the HAM-A is not valid-
Yeah
... until one week after.
Mm-hmm.
It's a one-week recall instrument. But we saw a multipoint drop in CGIS, which is obviously a general scale of overall disease severity that was statistically significant 24 hours after. So we're talking about people who, in most cases, have lived with severe anxiety for, in decades-
Yeah
... who, the day after a single dose of this drug, say, "I feel better." That kind of rapid and durable response is somewhat of the Holy Grail in, you know, drug pharmacology.
Now, you mentioned severe anxiety, these patients living for decades. I can tell you, this morning I had severe anxiety because I didn't know how this conference would go. I'm sure it's gonna go well, but I doubt I would've qualified for your study. But help us understand how you measure severe anxiety and whether or not you're going to be able to enroll these same type of patients, and then we're gonna get to some commercial questions.
Great
... or to future commercial questions.
So in our studies, we use a HAM-A, a Hamilton Anxiety Scale, which is the gold standard for anxiety research. We enroll patients with a HAM-A of 20 or greater, which is right in the middle of moderate category, and what we find is that in our phase two study, at least, on average, patients had a HAM-A of 30, which is quite severe.
Okay.
What we know from epidemiological research.
Mm
... is that 80% of patients with GAD have moderate or severe disease, and really an extraordinary number of people, upwards of 5%, are walking around with moderate or severe anxiety when we give them a screening instrument, the GAD-7, which is now being implemented. The U.S. Preventive Services Task Force recommended two years ago to implement general screening for any adults and adolescents for anxiety. A significant portion of the population is walking around with moderate or severe anxiety, not having ever been diagnosed and saying, "I don't have this disorder." There is a huge problem sort of lurking below the surface, and that's on top of what is already a diagnosed prevalence of around 6%.
What about that diagnosed prevalence? I assume that the patients who came into your study had been diagnosed and had experience with other classes of agents. Were they experienced with LSD?
... we have exclusion criteria for both recent use and-
Okay.
-historical use. But, in most cases, what we saw is, or I see, globally in the study, what we saw is something that looks pretty representative of the population, 10-15%.
Okay.
prior use of any psychedelic.
Okay.
Yeah.
This is a highly burdened patient population. These are not just guys like me who wake up a little anxious because I have to be on stage all day. They're people who have lived with this for a long time.
Lived with it for a long time, and it impacts every aspect of their lives. A story, we were at a clinical site last year, and talked about, obviously, with no names or confidential information, talked about, you know, a patient who had to quit their job because they were so anxious they couldn't handle going to work and going... being out in the world. They, you know, relationships suffer, general health suffers, healthcare utilization, the number of other somatic disorders that patients present with and go to the doctor for are really dramatically increased in this population. So this is a disorder that... I think everyone has transient anxiety, right? This is a sort of an emotional state, acutely.
But these are patients who, again, in many cases, have lived for ten years or longer with debilitating anxiety that touches all aspects of their health and their life. And to have them come into a study and then go into true remission, where they just don't have symptoms that you can pick up anymore, that is the really remarkable finding that we've had to date with this drug.
One could argue that anxiety is an important thing from a selective pressure standpoint. You gotta respond to being anxious, right? Do something about it. But it can result in chronic depression. So it's interesting that you're also operationalizing a depression study, yet you don't have any data that I've seen that suggests you do that. So what gives you confidence that you should move forward in not only GAD but also MDD?
So preliminarily, we have a collaboration with a group over in Switzerland that did a study of LSD in depression, and we saw-
Mm
... sixteen-week durable response, using somewhat, you know, unusual instruments. And then in our phase II study, we also saw, yes, there was a GAD population. They had to have GAD as the predominant cause of clinical concern, but these are patients who often are diagnosed with depression. They're not in a major depressive episode, which is a important distinction, but intrinsically, are going to have depressive symptoms-
Mm-hmm
... just simply because of how we measure them. The HAM-A and the MADRS, for instance, the depression endpoint are highly overlapping in terms of the symptoms that they assess. We saw patients have a in the mid-twenties on the MADRS, which is right below where we would expect patients to be if we were gonna enroll them in a study. We saw even there, statistically, clinically significant reductions in depressive scores after a single administration, so kind of a constellation of evidence that gives us confidence in depression. And sort of what we believe is that the mechanism here is something that is not directive to anyone's symptom cluster, that there's something perhaps a layer deeper that is actually being changed through the mechanisms of the drug, and that's going to have impacts.
We've seen historical studies also in things like use disorders, where-
Yeah
... where one day we also may have an opportunity.
So with operationalizing a big set of phase IIIs and then marching to potential NDA in maybe 2026, or certainly data, surely you're getting ready for a commercial initiative in the future. And so the question that I have is: Are patients going to be willing to, and are doctors, psychiatrists, going to be able to administer a drug that takes a day, basically, to do?
Uh, every-
How is that gonna work out commercially?
Every bit of research, and we’ve already started. I mean, we have a huge degree of confidence in the path forward, and obviously, if we're able to replicate anywhere close to what we did in phase II, we feel very good about the potential for the phase III studies to be positive. Two years ago, we hired a Chief Commercial Officer. We’ve already started to build out that team because we need to be ready. This is. It’s appropriate that we are having to do something new here. The system is not working. Patients are not being well served by what we have today. We’re going to need to make changes. We’ve seen a lot of those changes already starting to emerge with things like J&J’s Spravato, where-
Mm-hmm
... some of the physical infrastructure has adapted.
Yeah.
When we go out and we talk to providers, we talk to patients, we talk to payers, really every stakeholder that has to be aligned in facilitating the adoption of these drugs, and the recognition for the need here and the recognition that if we have a drug that can really do what we're seeing in the clinical research, you know, overwhelming majority of all of the stakeholders have been incredibly engaged and supportive. There are certainly pockets... There are demographics that represent a higher likelihood of wanting to use, you know, pursue these drugs as treatments. But, if you talk to a patient or a psychiatrist who treats patients who have lived with chronic anxiety, who have lived with depression, the drugs that...
The treatment options available today are just completely inadequate, and they have shown an enormous willingness to be ready to adopt these drugs if we ultimately are able to get them approved.
So you believe the concept or the paradigm of intermittent treatment of psychiatric disorders is here or is going to certainly be the case. I mean, we see it with Spravato. We see it with Zulresso in PPD, a little bit different, but, you know, and then all your innovation and that of other companies. We have a panel later on this afternoon. I encourage everyone to sit in and listen to it because we have a couple of KOLs who will speak to the future. But Rob, tell me, if you, if you get over the goal line with regard to good data, okay, in 2026, you know, this commercial paradigm starts to, you know, clearly get traction, how are you going to protect LSD? I mean, Bicycle Day has been around for quite some time, since, well, almost eighty years, right?
How are you going to be able to protect your drug?
It's one of the things we know this reality, right? We-
Yeah.
To be clear, we say this to everyone. We did not invent LSD. We're very much aware of that, and it has informed our thinking from day one about having to be intentional, to come up with innovations that can be patented. It is the reality that FDA has never approved LSD or any of these drugs in the classic psychedelics, and so it gives us a path for, at a bare minimum, marketing exclusivity. We just earlier this summer had a really key patent issued on our ODT formulation, so-
Okay.
Our go-forward formulation is using Catalent Zydis ODT technology.
Excellent.
We see both clinical benefits, but also IP benefits and market protection benefits. That takes us certainly well beyond the five years of marketing exclusivity, and because of the knowledge and the pace at which we're able to develop these drugs, it also gives us a path that our patent expiries would be on the longer side after an initial approval because of the time it takes us from today to already be able to embarking on a phase III study, and have that first patent issuance, you know, kind of coincide with that same timeframe.
It's been a fantastic year for you. The question that I have is, if we're sitting here in a year, what is it that you'll be most interested or most proud of having accomplished? You'll be before data, so what is it that you... What value creation metric would you like investors to use for the next year?
It's a year that is about, like, you know, everyone, us included, wants these studies to be completed and get to the finish line as quickly as possible because that means value creation for our shareholders. It means getting these drugs to patients faster, hopefully. The next year is certainly about execution. We've got three phase III studies that we are operationalizing now that will be reading out in 2026. We've continued. We're incredibly proud of the organization that we've built, which has still been extremely efficient. We're about seventy people-
Wow!
Who we are, we're launching a, you know, international phase III program and two indications, with a lot more coming behind it. So just continuing to bring in the kind of talent. In psychiatric drug development, we have certainly seen a sort of overwhelming interest by drug developers to get involved, they're seeing the potential impact this could have. And so to continue to bring in that kind of talent, to continue evolving not only our clinical development, but also laying the groundwork so that we can launch these drugs successfully, hopefully one day.
Silly Wall Street question: Do you have adequate capital to not only start these studies but see them through the completions?
We do. Yeah, we're fortunate to have, you know, some of our investors in the audience, but we've been incredibly grateful for the support from the Wall Street community, investor community this year. We've raised about $250 million of equity capital this year, which gives us a runway into 2027, 12 months or more beyond our first phase III readout in GAD. So, very well positioned and able to really operationalize not only these studies, but also lay the groundwork for that eventual commercialization effort.
We are pretty much out of time. Are there any quick questions from the audience? Anything... Dan, you want to add anything? The card-carrying psychiatrist in the audience, Dan Karlin, CMO. With that, I think we're going to call time, but I appreciate everyone's interest in the MindMed story. Rob, I appreciate you spending time with us today, and good luck on the next year.
Thank you. Always a pleasure.