Okay, all right. Thank you for joining the Oppenheimer Healthcare Conference. Next, my name's François Brisebois. I'm one of the biotech analysts at the firm. T hen the next story we have here is MindMed from the company. We have CEO Rob Barrow. W e do cover the stock with an Outperform. It's been very exciting times at the company, thank you very much, Rob, for joining. W e'll jump right in. I think in terms of format, we're gonna do a fireside chat from 10:00 A.M. to 10:30 A.M. here Eastern Time.
I f you have any questions to send, feel free to send them in the Q&A. If not, my email, which is francois@opco.com. A gain, Rob, thank you. And maybe just for those that are not aware of the company, maybe just brief company background on MindMed would be great.
Yeah, absolutely. MindMed was formed initially pursuing a couple of programs, and we've since expanded our pipeline, really focused on, as a neuropsych company, focused on the development of the psychedelic drug class. It's an area of research that's really had a renaissance over the past five or ten years now, and one where there's been a lot of focus in different molecules. W e're pursuing our lead program as 120, which is a proprietary form of LSD.
It's one of the most storied, most studied drugs in the class, and where we've now come to some modern clinical data that really establishes why that's the case. We have two products in the pipeline, in the clinic now. We'll be initiating our Phase III program for 120 in generalized anxiety disorder in the second half of this year.
We're in a phase I study for the R-enantiomer of MDMA, which we're developing, for the treatment of autism spectrum disorder.
Sorry, I muted myself. Great. So in terms of 120 that you, you mentioned there, you're going after generalized anxiety disorder. You see a lot of companies going after MDD, TRD, but you guys is GAD. I think what would be helpful here is just to set the stage a little bit. You had Phase IIB data in December 2023, I believe. J ust can you help us understand a little bit or just kinda paint the picture of what the design was, what the data was, and then, and we'll go from there.
Yeah, absolutely. G eneralized anxiety disorder is one of these indications that's been overlooked for such a long time. The last approval was Cymbalta in 2004, so 20 years ago. And since that time, the prevalence of GAD has tripled. It's an area that's fallen out of focus largely because the drugs we have available aren't particularly well-equipped to treat anxiety symptoms, and particularly as it's been so, benzodiazepines have fallen out of favor in clinical practice.
Really left with just a few SRIs that don't work particularly well to treat GAD. W e've got about 80% of patients who have severe GAD. W e saw a real opportunity to have to treat and hopefully be able to generate data long-term to lead to an approval for really the first and a game-changing treatment in GAD in a very long time.
In terms of study design, we embarked on a Phase IIb study. It's a 200-patient study, looking at five different arms in the study, four different doses of the active 120 versus a placebo. T hat was because, as is reflected in FDA's guidance from mid-2023, really there's been little dose exploration in this drug class.
There's been a sort of a lot of legacy and sort of historical assumptions that just because a drug is dosed at a level that makes the patient feel the effects, that that would be a good dose to pursue. T hat's really not how we view proper drug development should be pursued. So, we ultimately conducted this study, enrolled 198 patients, roughly 40 per arm.
The findings of that were particularly, you know, supportive of the approach. I think we're very, you know, gratified to see FDA's guidance also align with the design decisions we made. But it also gave us clarity. We saw a clear dose response. W e've now released a 4-week primary analysis from this study.
A clear dose response, with a clear delineation of different dose levels that actually have a clinical effect. W e also saw a sort of plateauing at the 2 highest doses we tested, which is what we desired to see, that the 100-microgram dose we tested was, you know, the best-performing dose we tested.
The 200 micrograms performed roughly similarly but had a slightly higher AE profile and a bit of a longer duration of time in the clinic and such. W ith all of that, we've really come out of this study with strong positive data that gives us a clear indication to move forward into phase III and a clear indication on the proper dose to take forward.
Okay. Y ou've mentioned a few times now the FDA guidance in 2023 that came out and how your trial kinda lines up well with the guidance. Can you remind us what is that FDA guidance? F or the space, what, why does it line up with what you guys were going after?
Yeah. W ell, several aspects. I t's a pretty all-encompassing guidance which covers everything from, you know, preclinical work all the way through clinical design and different aspects of clinical development that need to be understood to support approval for these products. T wo particular points that stand out, or really three points, I should say.
One is the fact that this is the first study of this size that has used a placebo control. With the serotonergic psychedelics, I'm excluding MDMA from that. I mean, MAPS, who's developing MDMA for post-traumatic stress has sort of likewise did placebo-controlled studies for their Phase III program. W e've seen this sort of exceptionalism occur in our drug class where there's different ideas about, you know, controls and this many other aspects.
Our view all along the way has been that the gold standard for research is to compare your drug against a placebo. T hen in order to help, you know, support the actual dose response, as I was saying before, we need to explore that fully and rigorously. T he fact that another point made in FDA guidance is the need for dose exploration, something we also did in this study.
Perhaps the most, you know, the most unique aspect of what we did compared to the field is that this is the first study conducted where there was no therapeutic intervention aside from the drug. There's a lot of talk about a, you know, psychedelic-assisted psychotherapy or things like prep and integration or psychedelic-assisted therapy.
All of these things are, you know, different words used to describe what is typically a highly intensive, you know, so therapeutic process that is carried out in addition to the drug in these studies. In our study, we eliminated all of that.
We effectively did what you would do with any other drug study: brought patients in, gave them informed consent, gave them the drug on a treatment day. They were administered the drug one time, kept under observation for safety, and then we followed them for 12 weeks thereafter.
To see the kind of data and the kind of impact we saw, after a single treatment in the complete absence of any sort of therapeutic intervention, something that's called out by FDA's guidance but also something that we think really gives us the best evidence yet of the real true standalone effect of these drugs.
Of the drugs. T hat's why you did the lack of kind of assisted therapy or whatnot is to really see the impact of the drug itself. Is that fair?
Yeah, that's right. I mean, you know, FDA has said itself. T hey don't regulate psychotherapy. They don't regulate the practice of medicine. Y ou know, just what researchers, what drug companies are required to do is to establish the safety and effectiveness of drugs. W e need to do that on a standalone basis without any sort of impact or, you know, confound of any therapeutic intervention. I t is a decision we made 2, 3 years ago but something that has now been really reinforced by that FDA guidance and something we feel gives us the strongest, most valid data ever generated with this drug class.
Right. I n the real world, how do you expect no therapy with an integration like, what are you guys – is this just to see, you know, the effect in Phase IIb, or are you gonna change that going forward in the Phase III? H ow do you expect to ultimately, if this is commercialized, what do you think the therapy, the assistance, the support might look like?
Yeah, that's, it's a great question. Y ou know, we don't expect to make any substantial changes to our phase III protocol. I mean, effectively, our phase II was designed as a phase III study. It just had five dose arms. W e obviously wanted to complete this study and land on a dose before going into phase III. In terms of the real world, though, and I think this is one of those topics that's been sort of conflated in the past several years with this drug class, you know, drugs with therapy almost always work better.
I mean, we know this for SRIs, for effectively any drugs. When drugs are administered in psychiatry along with therapy, the outcomes typically are better. We're big fans of psychotherapy.
We think that's a fantastic thing for patients. I n the real world, we certainly expect that, you know, depending on a provider and a patient's particular needs, that very likely they will have some form of therapy that gets administered. It just has nothing to do with a drug and the safety and effects of a drug. I n development, we needed to establish the clinical, you know, profile of the drug in the absence of that therapy.
I think the promising thing here is that in that context, whatever we're able to demonstrate, I think, probably is going to be an underestimate of the real world kind of durability and magnitude of effect that we could ultimately see.
If we can see these staggeringly large effects with a drug on a standalone basis, I think that could be even better out in the hands of practitioners in the real world.
On that point, what effect size with no assistance did you guys see at four weeks here in the Phase IIb?
Yeah. F or the backdrop, you know, the standard of care, benzodiazepines and SRIs have an effect size, a Cohen's d, of around 0.36-0.38. And that's the change normalized by the variance in the data. In our study, we saw an effect size that was 0.88, which, of course, is well over double that standard of care, as good as we've seen with anything to date.
Okay. Great. O kay. M aybe just for those to understand, you mentioned it quick, but what exactly is the effect size? What does that mean?
Yeah, effect size. I t's a way to normalize and compare really across studies typically, right? W hat we look at is because different studies have different variability in the data and different, you know, baseline characteristics and all these things, it's a way to normalize comparison. W hat it really is, is normalizing the change from baseline, so change to four weeks, divided by the standard deviation of the outcome.
T hat normalization allows you to say, "Well, in our study, we might have had X units of variation or standard deviation in a historical study or in a sort of meta-analysis of SRIs, for instance." You're able to pull these things. R eally that's what we're looking at and why we use that as comparison.
Really, no matter how you compare the outcomes from our study, that's just a convenience. When we look at the magnitude of change, it was really staggeringly different from what we've seen before. We saw patients who, on average, came in with a 30 on the Hamilton Anxiety Scale, which is our primary outcome measure, that had, on average, in the 100-microgram dose group, a 21.3-unit decrease through four weeks. I t corresponds to the 7.6-unit change over placebo. All of those are about double what you see with historical standard.
What's considered clinically relevant there for a change in HAM-A?
Well, for change in HAM-A, I think typically we look at over placebo, right? C hanges over placebo that would be considered clinically significant would be anything over 2.5 points would be clinically significant. T hat's why when we see the approved standard of care, most of the times it's a 3 or at most sort of 3.5-point improvement over placebo. I n those studies, the sort of absolute change in HAM-A that we see is typically around 12 or 13 units, which was interestingly equivalent to what we saw in the placebo response in our study. W e saw a 21-unit increase, which is, of course, significantly larger than.
How do you feel about that placebo response that you saw? 'Cause you guys did look at true placebo, super small dose, probably considered placebo to some. How do you feel about your placebo response, especially in this drug class?
Yeah. I t's a really important topic. W e talked about the guidance. It comes up there. It comes up in any sort of methodological discussions about researching psychedelics. The concern because of the sort of profound perceptual effects with this drug class is that it could generate a nocebo effect, that the sort of functional unblinding could result in a nocebo response, which then, of course, would overestimate the effect of the drug.
We've seen that from some studies, not in our study. In our study, we saw as strong a placebo response as we've seen in almost any historical study in GAD. Well, a few points there. One is that, you know, functional unblinding is something that is pervasive in psychiatric clinical trials.
There's not a single drug where there isn't some degree of functional and blinding. I mean, benzodiazepines, psychostimulants, Spravato for that instance, the associative effects of Spravato are really pronounced.T his is not something that is really that abnormal. The thing that we find really interesting is that as you start to compare across studies, I think that the intellectual sort of concept is that an expectancy bias that is then reinforced or not by functional unblinding results in this nocebo and impact on study and biased study outcomes.
W hat we actually think may be more at play here is that the therapeutic interventions, the psychotherapy, and these things that are happening, in other drug programs, when we see studies where heavy therapy or manualized therapy is being done, we often do see a nocebo response.
In our study, we eliminated all of that. M aybe what's actually happening here is that it's not the functional and blinding that's at play. It's the reinforcement, both before and after dosing, of the expectancy bias, that when you give therapy in addition to a drug, what you're actually doing and I've run these studies with other drugs, right, what actually happens is, the providers, the researchers are with patients saying, you know, "If you feel these effects during treatment, here's what could happen and why you're going to get better." T his sort of narrative forms. B y eliminating that, we kinda eliminate any risk of the nocebo effect in our study.
We think it if anything just bolsters the validity of our study results and really gives us perhaps one of the first, you know, true estimates of a drug effect and it's staggeringly positive, right, is good even in the absence of that overestimation. W e were really encouraged by that placebo response.
Can you just remind us what the response and remission rates were in the study?
Yeah. T here again, we saw dose-responsive signal in response, which response rate is, of course, 50% or greater change in remission in the HAM-A. We kind of conservative different cutoffs have been used. We conservatively used a HAM-A of 7 or less as being in clinical remission. At the 100-microgram dose group, we saw a 78% clinical response rate through week 4 and a 50% clinical remission rate, which is, of course, after a single treatment.
Single treatment. Yeah.
Unlike anything we've seen in psychiatry before.
Okay. What's very interesting in this space, and you guys a single dose, so you get a real look at the speed of response maybe on the first dose but also the durability. Can you help us understand what you saw in terms of durability, what you've shared at 4 weeks, how it's looking, and then maybe your confidence because I think you are expected to read out 12-week durability data this quarter. W hy should investors feel comfortable with the 12-week data that's coming?
Yeah. I t through four weeks, what we saw, and when we look at the sort of temporal relationship between HAM-A change, in this study, what we saw is that patients in the study got better as early as we could measure it. HAM-A has a one-week recall, so we can only validly measure it one week after dosing. W hen we measured it at week one, two, and four, we saw absolutely zero loss of clinical activity over that period. T here was no sort of reversion to the mean.
There's no reversion back to baseline or any sort of signal that patients were heading towards a relapse on average, which when you see a line that, you know, decreases and stays absolutely flat, that gives us a high degree of confidence that that sort of effect is going to continue on for a period of time thereafter.
We do have 12-week data. Of course, we're really interested in presenting those data and making sure that we're able to support it, you know, even at four weeks, which was the primary outcome and has been used as approval for other GAD treatments. You know, that is certainly enough to move forward, and we feel highly confident moving forward into a pivotal program.
When we think about the real world potential here, of course, these are treatments in MM120. Patients are gonna be coming into a clinical setting. They're gonna be kept under observation just for safety reasons for some period of time. W e wanna make sure even though those dynamics stack up quite favorably compared to Spravato, for instance, which is having great commercial success, the more durable the effects, of course, the better. W e've seen some academic studies and some real-world, compassionate use examples of 6-12-month durable clinical response after an acute intervention with LSD or MM120.
Yeah.
Really, you know, of course, if we can show through 12 weeks, that's as long as one can really reliably establish placebo-controlled durability in these studies just because of ethical concerns about keeping patients on placebo for too long. I f we see these effects persist out the 12 weeks, again, I think it'll be really something that no one else has seen to date and something that we'll get us even more excited about the real-world potential commercially and the path forward in the clinic.
Okay. You know, so we've touched on the efficacy. The safety looked good. You mentioned Spravato there, and commercially, it's really kicking off. It had a slow start a little bit. C an you just help really, for those that aren't aware of the space as much, why is the recent success in Spravato very interesting for, on the commercial side for you guys and just maybe remind people how people are treated with Spravato, what they have to do, how the clinics work, and just maybe really translate it into how this is a positive for your space?
Yeah, absolutely. Spravato, you know, is approved for major depressive disorder with suicidal ideation and treatment-resistant depression, marketed by J&J. You know, early days of Spravato, as you mentioned, really commercial uptake was slow to come by. It's not because of anything other than some sort of specific aspects of the commercialization and the REMS for Spravato. I think the early days there were something that was able to be corrected and which is a very much a lesson learned that anyone who's going to be developing an interventional kind of psychiatry drug in the future like us, we know where the hanging points are and where we need to get it right.
Part of the challenge is that Spravato is administered twice a week for the first month and then once a week thereafter. Each administration session is a required two-hour monitoring. Patients have to be kept under observation for two hours because of physiological risks associated with Spravato.
Is that two hours for the entire process, or how, how does the experience work? Is that two hours after receiving Spravato? Is it?
Yeah, 2 hours after administration, right? T hat's a great point and a point of differentiation here too that doesn't kinda fly below the radar often, which is that, for a you know, for a drug like Spravato, the 2-hour observation period is in addition to whatever prep time travel time for a patient or prep time and documentation time for providers.
O ne of the earliest commercial challenges for Spravato was that under the Spravato REMS, patient monitoring forms have to be submitted before the patient can be administered another dose, which created this huge logistical challenge that patients have to come in, be under observation, and within 2 days, providers have to complete the form submitted to the REMS and get cleared and get drug ready to go for the next administration.
When you stack up all the even just the time, even just those 2 hours spent in the clinic, it ends up being around 120 hours or more that a patient is spending in the clinic per year, 120 hours. Now, it's chopped up over, you know, 50-60 administration sessions. F rom a practical standpoint, again, when we go out and talk to providers and patients, you know, while it yes, it seems unique. It's sort of like surgery, right? You have surgery.
You go in for a day, and you're gonna come out with some durable benefit. That's really how we would envision the commercial opportunity with MM120, whereas Spravato is more like physical therapy or something. We have to go in every single week over and over and over and over again.
That can be even more burdensome both on the provider and the patient. The fact that we're seeing we're now approaching 4,000 Spravato centers around the country that are administering Spravato. W hen we go to talk to these Spravato centers as well, the feedback we get is that many are, you know, kind of ecstatic about the potential for psychedelic drug class and that if MM120 comes to market and some of them have said to me, "Well, you know, I'm doing Spravato because it's available today. A s soon as your drug is hopefully on the market, that's what I actually want to be doing."
Same, the same center. There's no rule for this center to not be able to. You'd use, ultimately, you'd probably use the same centers, right?
Yeah. I'd say as a baseline, we'd use the same center. Because of the unique aspects here too, I mean, there's really very little physiological risk that we've seen to date, both in our study and historical studies. T he Spravato requirement for monitoring was largely driven by these physiological risks, right, blood pressure risks.
Yeah.
In particular, we don't really see that with our drug. O ne of the things what's really interesting is that the locations that the requirements for a site and a provider to administer MM120 may be much less. O f course, this is something that it would be reserved for final labeling discussions and things as we advance in development and work with FDA to arrive at label. W e certainly believe that there's an opportunity to expand even beyond the kinds of locations and centers where Spravato is used today. T here's an even broader kind of commercial adoption that could be possible here.
Do you share your thoughts? It just, you know, for some reason, you guys have found a way to make efficacy expected in this space, which is wild in itself. A lot of questions turn into commercial. If you guys studied a little bit how clinics are, are physicians involved or anyone involved on the medical side, you know, the incentive in terms of kinda, you know, duration, the quantity, you know, just having multiple patients a day versus having one patient last longer, any news on that side that you'd like to share or?
Yeah. Well, it's really a great question. When we go out and do this work and talk to the providers, of course, we're trying to map and understand all of these dynamics. It is highly profitable for Spravato centers. I mean, reimbursement is good. Both, I think, something that gets overlooked is that reimbursement for Spravato, for instance, is both a medical and a pharmacy benefit. The medical benefit covers the monitoring time. T he pharmacy benefit, of course, pays for the drug. Now, the monitoring time is such that it's reimbursed on an hourly basis.
If, at a site level, if a site is paying their staff who's monitoring these patients for a full eight-hour workday, it's really important that they have revenue to match as much of that as possible. T hey have patients who are being run back to back to back to back to back to back in rooms and sometimes multiple rooms at a time. You compare that and the documentation, you know, to run five patients a day means you're doing five times the amount of work. You're doing five times the amount of setup. You're doing five times the amount of the documentation.
We believe, and we're encouraged by the dialogue we've had with these clinics and providers that there's a far more attractive dynamic of having one patient per room per day that's a pro, both from a provision of care and a sort of profitability standpoint. There's actually a strong incentive why there would be a reason to adopt our product over something that requires, you know, cycling through patients, multiple times a day.
Okay. Great. T hen maybe lastly, that's all very helpful. That's a lot of the questions that are coming in are around that space. T hanks for the clarity there. Maybe just lastly, you know, if you can touch on the ODT PK bridging data that might be coming and why that is important and just if you could quickly touch on, you know, your cash position. You guys were in a solid spot even off the data, which is kinda rare, especially in the last few years on the street. Y eah, maybe on the ODT and then just the cash position. I think we'll close it with that.
Yeah, sure. S tarting with the cash, ending Q3 2023, which is our last financials, we had about $117 million of cash on the balance sheet, which gives a runway. In addition to a credit facility we have in place, gives us a runway into 2026, well-funded to execute our phase three program over the next couple of years. In terms of the ODT formulation, it is one that is also we've tried to be really intentional about, you know, of course, clinical design and development, but also market protection one day. You know, I think something that gets lost often is the fact that a patent isn't protective if it can easily be worked around.
We spent the time to go explore a number of formulations and arrive at a formulation, which is Catalent Zydis ODT, which has been used for things like Biohaven's Nurtec ODTs and migraine. In our belief and we'll be sharing PK data this quarter, but our hope there is that we see faster absorption, that we see better bioavailability, we see a differentiated profile that you know is minimal risk in terms of changing in development, but would be very difficult to replicate from a generic or a follow-on applicant's perspective.
If we can see somewhat of a differentiated profile that'll give us a high degree of confidence that not only will we have, we believe, good IP, and we're just now starting to see some applications be granted, some claims be granted in different jurisdictions, but you know that we'll believe we'll have strong IP and that that IP will be differentiated enough that it'll be very difficult to work around and to you know have a follow-on product, which gives us a great opportunity for long market protection after approval.
That's great. You knocked out a couple other questions I had. P erfect. I think we're up on time. Thank you very much, Rob, for.
Thanks a lot.
For your time. Hopefully.