Capital Markets. Thanks for joining us and for being here. Our next featured company is MindMed, represented by their CEO, Rob Barrow, and their CMO, Dan Karlin. Thanks, Rob and Dan. Appreciate you being here.
Thanks so much, Brandi.
Great. Let's maybe kick it off on MM120 for GAD and MDD in the ongoing studies. It sounds like the studies are all, the phase 3s are all progressing on track based on your latest updates. I guess I'm curious if you could provide some more color on what you're seeing early on with respect to enrollment trends and conduct for the phase 3, how Voyage and Panorama are going in GAD, first of all, and maybe similarities and differences to what your experiences were from the phase 2.
Yeah, I'll start it off and turn it to Dan, but at a high level, we've been really, really encouraged by the early enrollment. I mean, everything we've done to design and operationalize our studies has been aimed at replicating the kind of efficiency and progress we had in the phase 2 program. So far, we're off to a great start. We've been, as I said, really encouraged. Dan, add any color.
Yeah, I think one of the upshots of having run the phase 2 program that we did is that almost entirely we've brought forward design elements from that phase 2 into the phase 3 program. For our folks, our staff, for the site staff and the sites and the PIs, they're in essence, in many cases, doing a protocol they've already done. Particularly for.
A lot of the sites are the same, I think.
Yeah, some of them. We've got many more sites. In part, that's because in the time between when we started phase 2 and now, a lot more capacity to do research in the space has emerged. While when we started phase 2, there were some pretty specialized sites working on these sorts of things, what we've seen in the interim is that high-quality psychiatry sites who are used to running phase 3 psychiatry trials have added the capacity to do session-based therapies like ours.
I imagine that's a trend we may see going forward as some of these types of therapies reach commercialization. How does that compare to the Emerge study in MDD? Guess what are you starting to see there? How does that?
I mean, again, when we think about the efficiencies of these particular studies, running a GAD study and an MDD study at overlapping sites at the same sites means that the recruitment efforts yield almost exponential benefit there because when folks come in, many MDD and GAD patients qualify for both diagnoses, right? If you've ever had a major depressive episode, now you're an MDD patient.
Which trial did I go?
If you don't have both, then they can only go into one or they disqualify. In our case, if folks come in in a major depressive episode and they qualify for the MDD study, they go into that study. If they come in despite having an MDD diagnosis, not in a major depressive episode with GAD, then they can go into the GAD study. The real operational efficiency is starting to emerge from that. Actually, what emerged, what we saw was that when we launched Emerge, two sites that were already running Voyage or Panorama, they in fact had MDD patients who had showed up, screened out, and were ready to go for Emerge.
That's great. Seems like really good potential synergy there. Can you remind us on the trial design, specifically the powering for your phase 3 GAD studies, and talk to us a little bit more about the adaptive study design features that Voyage and Panorama have and how those work?
Powering was 90% to pick up a 5-point difference between the 100 microgram group and the placebo, which is the primary analysis in both of our phase 3 studies in GAD and likewise in Emerge. As a reminder, in phase 2, we saw very much more of a response than that. We saw almost an eight-point delta between a 7.7-point difference between 100 and placebo. We want to be conservative, obviously, getting the bigger study sizes. We are very used to in psychiatry, effect sizes dropping as you get into pivotal studies. To be conservative, we assumed a 5-point delta, have 90% power. That gave us 100 patients per arm. It is based on a couple of other assumptions. One is a pooled standard deviation of 10 units and a dropout rate of 15%, a non-available rate in those studies.
The adaptive design, the interim sample size re-estimation, it allows us to maintain the power at 90% if any of those 2 nuisance assumptions, dropout or variance in the data, are higher than we expected. Obviously, there's no learnings about the delta between the active and placebo arms, and therefore we do not spend any alpha, but we do make sure that that power is maintained if there are a random distribution such that the variance parameter is a little bit different than what we expected.
Was it just standard deviation and dropout rate that guides this, or is effect size, does that go into the calculus for how much to increase the study?
Just those 2 nuisance parameters, as they're called. The actual effect between the groups, the actual effect size will not be assessed until the primary analysis once enrollment is fully complete.
Got it. If you were to increase the sample size, how would that impact the timelines for readout? What would your plan be for how you conveyed that news to the street?
We've accommodated that within our plan. Certainly there's sort of an exponential growth in any study's enrollment. Regardless of whether we increase sample size or not, we've guided accordingly.
The maximum by which you could increase the study size is already encompassed in your timeline guidance. Is that something we would just sort of see on ClinicalTrials.gov potentially?
I think we'll announce at the right time important data that would give any further clarity. Certainly as we get closer to the readouts, we'll be potentially able to offer a little bit more clarity about exact timing and such. At this point, we haven't said anything specific.
Okay. I know you're going to be doing open label extension follow-up and work. Can you talk about what specific safety or symptom severity criteria you're going to use to determine whether a patient might be eligible to be retreated with 120 during that kind of extension period? I guess how you've kind of defined and validated, because I know that's maybe somewhat of an unknown. The durability obviously looks good so far, but we don't know exactly how long it's going to go. Sort of how do you manage that in context of retreatment?
Yeah, I mean, there are a couple of interesting points about the extension phase. One of which is that unlike a daily drug paradigm where on the day that someone finishes their double-blind period, the next day they get open label treatment. While the allocation they were initially assigned to isn't revealed at that point, from the point they get open label treatment forward, they are known to be in a treated state. In this paradigm, because there's not daily treatment, it's reasonable to think that a large number of participants will remain in a blinded state for that entire year. We will be able to characterize the double-blind controlled effects of a single dose out to a year. Starting the week after someone qualifies for the extension phase by completing the double-blind period, they'll get monthly HAM-A assessments.
The threshold to be treated in that extension phase is 16. The threshold to enroll in this study is 20. Moving into the open label treatment, we're lowering the threshold there. That 16 represents sort of the category difference between mild and moderate. We expect it's reasonable to think that in the real world, people with moderate or worse severity would be treated. We make up to four treatments available, though we don't expect that to be the number that very many people get because we didn't want to rate limit those data. We wanted to actually see sort of a curve where we could describe what different types of patients, what different types of response patterns look like with that treatment available to them.
Okay. Presumably a fair number of patients originally randomized to placebo or a less effective dose could be eligible for retreatment or really what would be reverse treatment.
We certainly expect that there is a higher non-response rate in the placebo arm. Of course, we won't know what they were allocated to initially. Of course, when we do look at the data, we would expect to see that more people initially allocated to placebo or 50 end up getting earlier treatment in the extension phase.
Let's talk about the regulatory plan, because that's obviously going to be the next step once the phase 3 is read out. Given how some of the FDA leadership has evolved and come together, do you think that the regulatory bar for psychedelics is going to evolve as these trials get closer to reading out? Where do you think we stand? I know there's been last couple of years, there's been a lot more guidelines and guidance from the agency around what they're looking for. I know you've had really good engagement with them. Are things continuing to evolve, or do you think we're sort of at a steady state now with what the FDA wants to see?
I think as with any novel treatment or novel treatment paradigm, there's inevitably going to be an evolution in the regulatory framework and discussions around it. I really, in tremendous respect for the division of psychiatry and all the folks at FDA who have been engaged with us for the last five-ish years at MindMed and the good fortune of working with them even before that on this drug class. They've been incredibly thoughtful about the approach and trying to deal with some of the complexities that present themselves, but also hold to the historical standards. We're seeing more and more of that. We've had continued and really strong engagement this year with the agency. Even with all of the changes and turnover and things that have grabbed headlines for our application, obviously with Breakthrough Therapy Designation, it helps quite a bit.
You get commitment from both the division and senior levels of management to try to expedite development. That's what that program is there for. We've had really consistent, strong, thorough engagement from the division with timely feedback that's very clear and is very much aligned with what we want to deliver, which is the most complete, robust package that could be imagined.
Have you experienced any meaningful changes in your interaction with the agency in the past couple of months?
Really nothing that stands out as a meaningful change. We've continued to have really positive interactions and very, again, clear and extensive collaboration in approaching these challenges, but nothing that has stood out as a stark change in any way.
In maybe some of your recent conversations with policymakers and folks like that, do they continue to sound supportive of psychedelic therapies? Do they sound more interested even and supportive than before?
Yeah, I think, again, a lot of headlines and ink gets spilled around the executive branch, but we've been, it doesn't really matter across DC and really across the country and state and federal legislatures even, we're getting just broad support and broad engagement and an interest to really identify how this can be efficiently moved forward. The need is, we don't even need to comment on the need almost. Everyone is aware of the credible vast need in these populations. The promise of the data has really captured everyone's excitement. I think that is really showing up in intangible ways across the board. It's not one party or one group or one position. It's really throughout every level of government where we've engaged, we've been really encouraged.
I think one reason that we are able to engage smoothly with policymakers is that for the most part, our message is don't think of this as something that's radically different from what's come before it. That everything we're doing in our development paradigm leading up to a potential commercial launch is to say, yes, these drugs have remarkable properties, but nothing about this needs to be treated as completely new. There's precedent for everything here. There's precedent for people having their consciousness changed by medicine. We've had anesthesia for 150 years. Where possible, we try to give that message to policymakers so that they can relay to one another and in their thinking that we don't have to treat this as some big, bad, big, weird new thing, that we're trying to do this in as familiar and recognizable a way as possible.
You're running both traditional phase 3s. That makes a lot of sense too. Given some of the setbacks from some of your competitors, MM120 may be the 1st or one of the 1st psychedelic therapies approved for a psychiatric disorder. There will be a lot of commercial groundwork building that you guys will be doing. Can you speak to some of the efforts you've made so far and how you're planning to approach commercialization broadly?
Yeah, we're really fortunate to have a new addition. Matt Wiley came on as our Chief Commercial Officer, who's incredible experience with complex launches and complex products. Those with REMS, those are controlled substances. We as an organization and with Matt especially have really, I think, supercharged our engagement and our thinking about how we carry the operational excellence from our development program forward into a commercial setting. That includes engaging payers, providers, patient groups, legislatures, as I said, I mean, really just across the board, being thoughtful about the infrastructure and the world that needs to exist to lead to rapid and expansive uptake of these drugs. It is a world that doesn't entirely exist today to the scale that it could.
Even the infrastructure that is available today is quite large and has grown really rapidly just in response to the availability of esketamine and ketamine and such. We see opportunity far beyond that. We see a wide recognition of the need, a wide recognition of the potential, an understanding of what's going to be needed to get this done at scale. I think, again, I think the thing that can often get missed is just how we need to orient. If we have providers who are enthusiastic, which we do, and we have patients who are in need, which we do, and we can deliver a product that meets that need and that's profitable for those providers, all the ingredients are there. Payers tell us, yes, we're going to pay for this. We understand the dynamics.
We're going to find a way if the data really are as good as what we've been able to generate so far. A lot of work to be done, a lot of the finer details that need to be worked out, but just at a very high level right now for where we are in development, all the signs we have and all the data we've been able to gather are extraordinarily encouraging about the theoretical potential and then the practical uptake of that into the real world.
Let's talk about the practical real world uptake, because I think that's an area that maybe there's less, maybe the street understands a little bit less and is looking to learn more about. How should we think about the patient journey and what logistically will be required to deliver this drug in terms of just the type of center and how many centers are out there right now that are equipped? What type of personnel would be needed to be at the site to monitor the patient and administer it? What type of payment structure would enable kind of reimbursement for a treatment of this nature where you'd be in a room for a long period of time during the day, but then really wouldn't need to be treated again and wouldn't need therapy for psychotherapy before that or after that?
How does it all sort of come together? What's in place and what needs to be built?
Yeah, maybe I'll turn it to Dan and talk a little bit about it. Yeah.
Yeah, so everything we've done in our development program is meant to make the commercial target as wide as possible so that where we've assessed safety, we've made sure that there is not a physiological risk to the drug. So physiological monitoring can be eliminated. One of the blockers to Spravato's uptake was that it requires physiological monitoring. We don't think we have physiological liability, and we're gathering the data to demonstrate that. In the world of interventional psychiatry today, there are 4,000 to 5,000 clinics. The data on those is always a little lagging because it has to be pulled out of the REMS applications in this. That's a number that's going up. Even as we speak today, there are more people opening more clinics to deliver interventional psychiatry. Interventional psychiatry in those clinics today is Spravato and TMS.
Any place that can do Spravato or TMS can be a launch target for MM120. The requirements really are a place for a patient to be that's comfortable enough for them to be there for the day and a way of monitoring that patient for psychological needs. Does the patient need reassurance? Are they comfortable? Do they need a snack? Do they need to go to the bathroom? Most of the rest of what happens, that is the effect of the drug, just happens. It's not mediated by the other person in the room. There's no psychotherapy requirement. There's no structured intervention requirement. All that's really required is assistance and sometimes comforting people as they go through that experience. That's an easy core target, right? Clinics that today do interventional psychiatry, APA, the annual meeting of the American Psychiatric Association was Saturday to today.
I came back from that last night. There were half a dozen dedicated sessions to essentially our drug, to psychedelics. I have never before seen a phase 3 asset getting even 1 dedicated educational session, let alone half a dozen. There is tremendous demand from psychiatry to be able to do this. Beyond centers that exist for the purpose of interventional psychiatry, our development program is also oriented toward can this drug be used in more conventional psychological and psychiatric settings? Could an individual therapist who has a place they do therapy be a session monitor for a day instead of doing, say, 8 hours of psychotherapy? By all appearances, based on the data that we have been able to gather, there is no reason that that could not be the case. Prescribing of the drug will look like prescribing any other psych drug.
It'll be billed under the usual E&M codes. It will be done in whatever length visit the prescribing psychiatrist or mid-level thinks is appropriate. That already exists. The question of monitoring is an interesting one because that sort of service, psychological monitoring, already exists in the E&M coding system and it's time-based. Really all you need to be able to get to a place where payers are paying for the five to eight-hour monitoring session is contracting with payers so that now they expect to see an hour of initial monitoring, 5 hours of add-on monitoring, and they reimburse it at the negotiated rate. While, again, a lot about this drug seems exceptional and certainly the evidence of efficacy we've gathered so far is exceptional, the infrastructure, the systems of care, they exist today.
That's a really important point. What about Europe? Have you had any discussions with European regulators and any sense of what the commercial infrastructure might look like there?
We've had a lot of discussions across the board in Europe as well. We have a good understanding. I think we're, as an organization, from a commercial standpoint, laser-focused on getting the U.S. right. That's where certainly the largest opportunity is and where we have organizational know-how and the capacity to build out that commercial infrastructure. That's been our first and foremost focus as we think about the commercialization. We are continuing to make progress, both development, regulatory, and with commercial payers and everyone over in Europe to make sure that that opportunity is something we can harvest as well.
Great. In the last minute or 2, maybe talk quickly about your other program in autism spectrum disorder and your expectations for MDMA there, potential timelines for the phase one and maybe some of the preclinical work suggesting that pathogenic molecules like MDMA can drive a benefit in that population.
Turn to you again.
In the minute 30 left, we'll talk about the other program we're doing. We're developing our MDMA, the right enantiomer of MDMA as a potential daily drug in autism spectrum disorder. The properties of our MDMA versus the other enantiomer, versus the left enantiomer, is that it seems to be stereo-specifically the serotonin-releasing enantiomer of MDMA, while the left enantiomer is much more amphetamine-like, much more dopaminergic. In order to get to a place where this can be possibly done, we've had to do safety studies, obviously. Based on a single ascending dose that we've established, we will be able to move that forward into an ESOE study, an early sign of efficacy study, where effectively we have every reason to believe that 1 dose of this drug does everything that multiple doses of the drug does.
We have every reason to think that we will be able to take folks with ASD into a space, in essence, where we can monitor them for their social skills, their communication skills, their empathy, their ability to self-reflect, reflect on others, and give them a dose of the drug and look to see if we get the effect we're looking for. That'll give us enormous confidence to be able to bring the drug forward into a multi-dose paradigm.
Great. We're just about at time. Great to see you guys. Thanks again and thanks everyone.
Thanks, Fran.