All right. Good afternoon, everybody, and thanks for attending CITI's 16th Annual Biopharma Conference. I'm Neena Bitritto-Garg , one of the biotech analysts here at Citi. For our next session, I'm really happy to be joined by the CEOs of two companies addressing mental health conditions through studying psychedelic drugs, including George Goldsmith from Compass Pathways and Florian Brand from atai Life Sciences. Over the next 45 minutes or so, we're going to talk about the potential for psychedelic medicines and mental health conditions, as well as some specifics of each company's programs. Before we do get into the discussion, if anybody listening has questions that you want me to ask, feel free to either email me directly or submit your questions through the web portal, and then I can incorporate them if there's time. Now I wanted to just turn it over to Florian and George to each give kind of a quick introduction. I do not know if we want to go alphabetically. Florian, you want to go first, and then George.
George, yeah, happy to if you want to take the lead, George.
Sure. Compass Pathways is a mental health care company looking to transform the patient experience in mental health care. Our goal is to provide accelerated patient access to evidence-based innovation in mental health. We do that by really focusing on breakthrough areas of new models of care where we can integrate digital therapy and powerful medicinal catalysts. In that case, we're using psilocybin as our initial program. We'll be talking more about that. Our focus is being a mental health care company transforming outcomes and patient experience through our research and through the tools that we create.
Great. Yeah, atai and the two of our companies share some history together. We were leading the Series A and B round of Compass. We know each other since quite a while in the meanwhile. Go back some years a tai was founded three years ago, actually shortly after Compass Pathways. We share kind of the very, very same visions that we need more efficacious therapies available for mental health patients. Once we realized that there's a lot of potential in psilocybin, we also realized that there are very interesting other psychedelic compounds such as ibogaine, ketamine, where we're developing one of the enantiomers, as we can discuss a little bit later. We really saw an even greater potential beyond psilocybin.
That is why we decided to start atai as a company that is really focused to demonstrate the safety that those compounds initially focus on psychedelics, demonstrating that those compounds are safe and efficacious. Really a heavy R&D focus here on our side. We ventured out more broadly and are, in the meanwhile, very much agnostic when it comes to mechanism, compound classes, et cetera. I have also, yeah, a lot of non-psychedelic compounds in development that we are equally excited about, in addition to some of our also digital therapeutics that we are also developing.
Perfect. To start off, and you both actually touched on this a little bit, but I guess if you can tell us a little bit about just kind of the genesis of both of these companies and how you got kind of involved in this space, in the psychedelics kind of drug development space, and then also just like what your near-term and long-term visions are for kind of how psychedelic medicines should be incorporated in the treatment landscape for mental health conditions. I know it's a very high-level, broad question, but I'd appreciate any thoughts you have. Whoever wants to go first.
I'll get started on that because we started on the journey a little bit before. First of all, I think it's important. While everyone's terribly excited about psychedelics, really the huge unmet need is in mental health care. What we're really focused on is transforming patient experience and outcomes in mental health care. The way we got started was a personal sense of experiences with our family. Our son became incredibly disabled with depression, OCD, et cetera. We looked for care at some of the leading institutions. It seemed like trial and error in medicines, and it kept getting worse. We nearly lost him. I think that this for us was a wake-up call to the need for innovation in mental health care. My co-founder and life partner is a doctor, a physician.
She was shocked at kind of the state of psychiatry compared to other areas of medicine. Out of that, we realized that there was a huge opportunity for innovation. As we looked at areas of potential innovation, we saw very much the promise of psilocybin. She woke me up after reading a paper, said, "Hey, you were in the 1960s and 1970s. What do you know about this?" That led a journey where we became familiar with the re-emergence of this research, became key donors in the area for some of the academic studies, but also realized very deeply that there was no path forward from the small studies into patients. My past background prior to that was working on what is not an oxymoron for many in the audience. It's actually regulatory innovation and really looking at how do we accelerate access to medicines. We are bringing a lot of those concepts into how do we integrate digital, how do we integrate psychotherapy and a powerful medicine into a new model of care to create transformative outcomes. Florian?
Yeah, thank you. I think nothing more to add there, essentially, because I think we very much share a similar background in the sense of why we got involved. As many know, Lars was a co-founder of myself in a different context when we started a company in a different field, and then joined Compass Pathways after he found help and healing in a psilocybin-assisted therapy in a jurisdiction where it is legal. Kind of seeing him going through this very, very troublesome phase and finding ultimately healing in alternative approaches that he then tried based on the clinical data that was produced in the academic studies was really encouraging to double down and then get involved similar to what George says to really make a difference in a true leap forward for patients that have not really seen any true innovation since 20, 25 years. That's really kind of the main driver for all of us at atai. I think that's what we definitely share with the Compass team.
Two mission-driven companies really looking at how do we change outcomes in mental health. We certainly need to do that. It is bigger than all of us.
Absolutely. Just kind of regarding because there's a lot of questions that I get kind of from investors around the use of psychedelics and kind of the history of psychedelic drugs. Obviously, one of the things that both of your companies have talked a lot about is the importance of co-administration of psychedelic drugs with extensive kind of psychotherapy. I guess, can you each kind of give me some of your thoughts on just kind of the whole process that a patient goes through as it relates to taking a psychedelic drug kind of for a medical use? What part of kind of that process of the prep, the dosing, and the integration do you think is really the most critical to ensure that the patient has a positive experience and that the benefit is durable?
I'm going to start out with that just because we're doing just finished our phase II B trial where all these things had to come together. It's not extensive psychotherapy, to be very clear. It's actually a very focused process. The way to best think about this is a protocol in which a powerful medicine is delivered under support. Regulators, the model that really worked for regulators was thinking of almost like chemotherapy where there's a protocol and a powerful substance and a follow-up treatment plan. For us, what we do is we have to take people off of their existing SSRIs if they're on them because that has a dampening effect on the effect of psilocybin. That washout is done over a couple-week period with support.
Some patients need more or less, but that doesn't seem to be a problem in our study or in other studies that have used a washout period. They have two preparation sessions basically to help them understand what the experience could be like for them, to understand some of their issues with the therapist. That therapist really is providing psychological support rather than psychotherapy. That psychological support then is used in the actual session. There are two preparatory sessions accounting roughly an hour each. They then have a powerful high-dose psilocybin experience in the high-dose condition or medium dose or a very low dose in our phase II B trial. There is a six- to eight-hour dosing period with the patient and the therapist. That's given with eye shades, soundtrack.
It's a deep inward experience with a supportive therapist there should there be any kind of encountering of challenging material or a need to share insights. The following day, those insights are processed with that therapist. There may be additional integration where people think about how to create an action plan for their life. If you think about depression and many mood disorders as actually a story and narrative that deeply grips people, it's lots of rumination, lots of negative valence to it. Psilocybin and our work in this substance seems to reset that. Therefore, there's also indications of a period of neuroplasticity, which could be used to accelerate learning and a new way of seeing the world. A new narrative can emerge. The integration's about that. It's really impossible to say which part is most important.
No one could ethically do a study where we do not prepare people and see how that compares to people who are prepared. This is really a protocol that has been developed, and it has been really modernized from the work that was done many, many years ago. Sorry, I went into so much detail, but it is a novel approach. That is done as an episodic monotherapy, really important. No other medicines on board, no other augmentation. This is a single experience with a durable effect. That is what is so radically different about it. The durability, since it is different in different patients, gives us an opportunity to use digital phenotyping to really understand how we get to the holy grail of psychiatric care, which is being precision, predictive, and preventative. That is really our focus in this work and where it is afforded by this unique substance.
Okay. Great. Florian, I guess, do you have any thoughts?
Yeah. I mean, for us, it really depends kind of as we have a very broad pipeline, right, a very broad portfolio of 11 drug development programs. Half of them, again, psychedelic in nature. For those compounds, it really depends, again, on the compounds, how we structure that preparatory dosing itself. Also, the time window varies. The durability of effect varies on a compound basis. We are equally convinced about the potential of digital therapeutics to increase efficacy and safety of the therapy, as well as, in our case, also ability to block, as we're often working on naturally occurring substances with quite some history, as well as ensuring scalability. Basically, how can we optimize the therapist's time to really deploy their time where it matters the most? We believe that digital therapeutics can be a key ingredient to ensure that scalability going forward.
Absolutely. No, that makes sense. That was actually going to be my next question. I guess, George, any additional thoughts kind of on your end in terms of the potential for digital therapeutics and scalability kind of of the commercial model?
I think, yes, absolutely. Everything that Florian said, obviously, looking at digital phenotyping, this idea of how we can anticipate and predict and prevent any relapse in what are typically chronic relapsing conditions is a huge value proposition for payers and for patients. On the therapy side, what's interesting is not only using these different tools, but the data derived from those tools. How do we improve the delivery of therapists? How do we improve therapy itself? I think one of the real powers of work in this area is that the medicine, the actual drug product, is almost like hardware. It constrains. It is something that will have a longer life. All of the learning, the digital tools will advance and be based on the learning in the real world.
This gives us an opportunity to optimize therapy models, optimize outcomes through the data derived using everything from natural language processing, machine learning applied to the actual content. What we really need to do is to look at how do we create a deeper understanding, not of mechanism of action alone, but mechanism of change. What changes and how do we accelerate and broaden those changes in patients' lives?
Got it. That makes sense. I guess just thinking kind of about the commercial model, right, one of the questions that I've gotten from investors is around Spravato and kind of the pace of that launch and what's working well and what isn't in that launch. I guess, how do both of you think about that, kind of the precedent that this Spravato launch has set for psychedelic or psychedelic-like drugs? How do you think your kind of model can improve upon what we've seen so far with Spravato?
George, do you want to take this or?
Yeah. I just feel like I've been talking a lot, so if you want to start, Florian.
Sure. Yeah. I think, yeah. I think in this case, it actually is helpful not to be the first mover. I think both of our companies were very early in the space that allowed us to evaluate, in our perspective, every compound or every treatment modality and every kind of angle that makes sense in terms of medical innovation and mental health. Here, I think it's good to actually see some lessons learned from J & J's rollout. I think that we all, I guess, as a space, as an industry, can benefit from to kind of, yeah, incorporate those learnings into kind of the second or third follow-on drugs that hopefully come to market. I think there's a lot to be said around stakeholder education. These therapies are very much paradigm-shifting in nature.
They are very much different than anything that psychiatry has had in the toolbox in the past. I think talking to also, I guess, on the reimbursement side, early on involving payers in the process to getting those therapies eventually reimbursed is key. Talking early on with therapists. I think, luckily, now the awareness around the potential of those compounds is definitely greater than five, six years ago. There is a lot of interest in the key opinion leader field that will also greatly benefit kind of the potential rollout of the compounds that Compass or atai is currently developing as there is quite an excitement building among, yeah, practitioners, at least in our perspective. These are kind of some thoughts where we need to, I guess, start in early.
A lot of the therapies that we develop actually fit right into kind of the treatment window that also Spravato is looking at. We actually want to kind of leverage that to our window. That's kind of how we optimize our compounds and development in terms of durability effect so that we also here can benefit from currently infrastructure that is being built out so that we need to reinvent the wheel, but kind of slot some of our compounds, our treatments into this treatment paradigm. These are kind of some thoughts on the Spravato rollout.
Yeah. I would agree with everything that Florian said. They were first. They learned a lot. We can benefit from that learning, are benefiting from the learning. I think in my past life, I worked to create something called Parallel Scientific Advice in the European Medicines Agency with the European Medicines Agency, which really brings payers and regulators together to design trials before, not after they're conducted. We use that even before we formed the company. We've used it several times, engaging payers early. Regulatory approval is seeing the starting line. It's not crossing the finish line. That's been embedded in our development process with health economic indicators in our phase II B trial as well as digital endpoint. We're really very much focused on designing this for the 21st century.
Great. Now that makes a lot of sense. Another question that I get frequently kind of around the development of psychedelic drugs, especially naturally occurring ones, is around IP, right, IP and exclusivity. I guess, can you walk us through kind of at a high level your general IP strategy? I know you have different programs in the pipeline, but yeah, that would be helpful if you could just kind of walk us through high-level thoughts and then any specifics, particularly kind of for George, obviously, for COMP360, specifics kind of of the IP and your thoughts on I know there's been some questions around the recent challenge in the U.K. If you could talk a little bit about that too, that'd be great.
Where were you starting off?
Yeah. Yeah. Have you decided? We at atai, I guess, more broadly are focused on, I guess, mental health, again, agnostic when it comes to therapeutics. Hence, I guess our approach might slightly differ from Compass in one or two areas. We have kind of everything currently from composition, overuse patterns to formulation. More broadly, think about IP as part of our ability to block strategy, including our digital therapeutics. Basically, the combination of the compound and the app as a kind of companion app. It's a little bit like a drug-device combination. On the IP side, we are again exploring everything around formulation of PK/ PD, parameter optimization. Again, we talked about durability, r oute of administration is a big one.
As we kind of want to get those compounds in the best, safest way to the brain, there's a lot of innovation potential here. Really thinking along those lines around formulation, manufacturing, and use patterns and composition of matter, of course, like we talked about, which is the latter, which is less relevant for the psychedelic companies that are around. Also here, looking at second- and third-generation molecules where we look at how we can optimize those compounds in terms of, and George talked about neuroplasticity, downward regulation of the default mode networks, so what's actually driving the efficacy.
Here, we are researching different areas and will eventually have also here a more robust IP, given that these will be considered composition of matter if we basically show what we intend to show in terms of efficacy and safety with those new leads that we have in development.
Just building on that, I think much of what Florian said certainly applies to us. We have eight patents that have been granted right now. More announcements forthcoming. I think obviously, this is an important area to continue to build upon. First and foremost, when we talk about protection, we have stuff to look at data exclusivity and market exclusivity afforded by regulation. Psilocybin is actually a new chemical entity despite its history because it's never registered before. We have all of that that's part of an NCE, a new active substance from a regulatory sense. Then on the patent estate, I think what we discovered is that the prior art simply didn't create the scale and the purity that was needed. We used that plus formulation difficulties to create a polymorphic strategy.
It's kind of geeky and technical, but has served other companies well in terms of NCE approaches for that particular polymorphic form. We've been struck by how early some of the challenges have been, both pre and post-grant. That means we must be onto something somewhere because you rarely see those that early. There was a non-binding opinion offered around in the U.K. That's a non-binding opinion. It has no effect on any of our filed patents. Obviously, there are people who are watching and looking at this strategy, which we're quite comfortable and confident in. As we add technology and more indications, we're using all the tools that we can to create a robust value proposition to really look at getting the investment we need to transform mental health at scale.
Absolutely. Now, that makes sense. There is also, I know both of you are also working on efforts to create kind of novel therapeutic or, sorry, novel psychedelic drugs, drugs that are targeting, right, like 5-HT2A, where you can kind of tailor the properties a little bit more deliberately, right, like the duration of the psychedelic experience and things like that. I guess, can you talk a little bit about some of the efforts that each of you is kind of undertaking on kind of that front? What also are kind of your thoughts on, I guess, the give and take between safety and efficacy when actually shortening or prolonging the psychedelic experience?
Florian, why don't you start, and I'll dig in a little bit to what we're doing.
Sure. Happy to. Yeah. I think I mentioned earlier, we are also exploring how to treat those molecules in a way that they maintain the efficacy. We shorten the duration to ensure a more scalable approach. These are kind of the third-generation approaches that I mentioned earlier. That's basically happening at our drug discovery engine called Entheogenics, where we're basically exactly doing that. I think there's also intellectually, academically, very interesting research going on. Again, what's driving the efficacy, right? Is it neuroplasticity? Do they need the psychedelic effects? I think there's a lot of interesting angles here to be explored. It's early days. I think what's important is that we have a scalable solution at hand. If we have a compound with a psychedelic effect, how do we deploy it in the most scalable way?
Here, we're, again, interesting in kind of the one or two-hour range. I think that there's a reason to believe that this is based on prior evidence in humans. That's kind of what we always look at when we onboard compounds. What's actually the prior evidence out there, at least anecdotally in humans, that points to efficacy and molecules like DMT and others where we believe that we can, yeah, through also an appropriate route of administration, achieve a one or two-hour treatment window. We believe that's a good hypothesis to start that we can demonstrate efficacy in a shorter time duration. There are certainly also companies out there that maybe try that in a very, very short duration where we are, at least at atai, are rather skeptical. We're not necessarily testing the extrema of 12-hour trips and 5-minute trips, but think somewhere in the middle, there's sufficient reason to believe that this is a reasonable approach.
Yeah. As we started our plan, it's really important. We have, given the mission that we're on. Our job was to figure out how the fastest path to helping as many patients as possible. It's why we started with psilocybin and built the organization around it. It enabled us to go quickly into a phase II B and then into a phase III program. That helps more patients. That's why we exist. Obviously, optimizing that through shorter acting is important. No scientist we've talked to understands whether this downregulation of the default mode network is a switch or a length of an experience. Does the experience length matter? We need to look at that. I think, Florian, in this one to two, three-hour window, it's interesting. All that does is leverage the existing infrastructure for greater throughput to meet the huge unmet need.
Let's get that all built with psilocybin and obviously building on the work done in ketamine, the infrastructure for that. Our whole focus here is really around what is the nature of the experience that is usable and a basis for changing a person's narrative, a view of their life. We're quite skeptical, I think, with Florian as well, of these very rapid experiences where people meet aliens, they talk to entities, they come back, it's a shot from a cannon, and what happened to me, and with high levels of issues around reenactment or flashbacks and so forth. I think patient safety, absolutely front and center, patient experience shortly behind. We were looking at all of this.
Our primary focus is reaching patients as quickly as possible with the most safe and effective approach using psilocybin and then using that as a foundation for others. We have a large number of compounds going into screening, and we expect to see some of those, some of these shorter acting, but similar durability of action over the next 18 months. Focusing on that. Obviously, the last thing I would just say is because we're so focused on building a robust infrastructure for late-stage trials, developing payer propositions as part of those late-stage trials, we're happy to partner with any organizations that have earlier stage infrastructure. The infrastructure that we'll have in phase III coming out of our 10-country, 22-site phase II program, radically expanding that, I think is a very attractive proposition for others. We're really focused on the late-stage path to patients.
Definitely. That makes sense. I just want to talk a little bit about conducting studies with psychedelic drugs now. One question from investors is around how do we think about translating data from investigator-initiated studies that are relatively small, right, single-center studies typically into a larger, rigorous, double-blind, placebo-controlled, randomized, multicenter international study, right? How do we think about that? Because that's obviously in psychiatry in particular, that can be a tricky thing to kind of navigate when you go from these smaller single-center studies to a larger global study. Yeah, how should we think about that, both just the general dynamics of that and then as it relates specifically to psychedelics, if there's anything to keep in mind there?
I think that first of all, this is about developing this medicinal catalyst that we surround with technology and therapy to produce an outcome. As such, we're not going to defy history. My headline of how to think about that, best word for me is cautiously. What's what we've done? Obviously, there's a predominance of signals that are similar, which is what gives us such confidence in the design and development of our program. All the concerns are, right, that's why we're doing this program. There's never been any dose-finding studies which we need to do, right? Our whole phase II program is very much focused on identifying the most safe, tolerable, and efficacious dose. These are things that we need to look at going into longer and later-stage trials. Obviously, there's also a question of the population.
Do we have a bunch of people who have been in earlier studies who like psychedelics, found them useful and come into the studies and find them useful again? How do we think about that? We have spent a lot of time working with regulators on limiting the upper number of people who have had prior psychedelic experiences so we can look at the generalizability, which has been one of the concerns of some of the smaller studies. You basically take that learning, do the best you can, put it in your studies. It is what we are doing. I am sure it is what others do. You do the work. That is what we are doing. We have the largest study ever done following the second largest study in healthy volunteers ever done. We did the first largest study in healthy volunteers, largest study in patients right now. End of year, we'll be reporting out. I think we'll be able to answer this question better come the beginning of next year.
Absolutely. Florian, I guess, do you have any thoughts on kind of translatability?
Yeah. No, I think completely agree with everything that George said. I mean, it's key to our approach, right? We heavily rely on the prior evidence out there. It's certainly, in our perspective, a very valid approach to, in general, de-risking drug development in an area that has proven to be quite tricky. Those signals are, and I think it's also worthwhile mentioning, often, even though academic studies, they're really large effect sizes. Even if you kind of think about that multicenter trial might kind of decrease that effect size by some degree, there's a good starting point that makes us confident, gives us reason to believe to explore those compounds further and generate the data that is needed, of course, then to kind of make the next decisions, right?
Absolutely. No, that makes sense. Just one more question kind of on clinical trials and running clinical trials with psychedelic medicine. I know, George, we've talked about this a lot in the past, but just kind of the issue of expectancy bias and the potential for unblinding. I guess, can you talk a little bit about what you've kind of done in the study, specifically for COMP360, and how you're thinking about addressing those issues? Florian, you're obviously welcome to comment as well as it relates to how you're thinking about some of your programs.
Our whole focus is early and often engagement with regulators because it's much better to engage before than after. This has been a really interesting and interesting for regulators question. The way it's been addressed is we do the best we can on blinding. Obviously, we have to prepare people for a high dose. They may not have that high-dose experience. That can lead the patient to perhaps suspecting that they received a lower dose. Therapists who support this are also blinded, obviously. The study team's blinded to this. Sometimes you could see some differences in a high dose, low dose, which led us to the final blinding, which is the blinding of the ratings. This is what really matters, right? What we've agreed is that to be working with regulators to agree a remote, completely blind assessment of MADRS that is administered by phone.
We have lots of MADRS across the studies because we really want to understand the durability of a single dose, remember, of episodic monotherapy. I think what we do is the best we possibly can in this. The regulators know it's difficult for expectancy. We all agreed on somewhat unusual strategy, which is let's equate expectancy by telling everybody you're getting psilocybin. That was seen as a best, as an emerging best practice. It's now been supported as a best practice in these kinds of trials because you equate expectancy. Everybody expects that they'll get it. The question is, do you end up in these kinds of trials where you don't have ongoing interactions, ongoing dosing?
Do you end up creating what's called a nocebo effect rather than a placebo effect where essentially people who are waiting for the full-on big experience that they're prepared for from a safety perspective, they don't receive that. They have a narrative that says, "The world doesn't treat me well. Things are not going to work out. And here I failed this trial." Does that actually worsen the depression, which increases separation? That's a concern for us. It wasn't a regulatory concern. Obviously, it's a patient concern in the trials. I think that gives you probably more than enough to think about in this area.
Yeah. From my side, nothing further to add except what George said. I think really looking at what matters for us, it's how do regulators position themselves. So far, they don't seem to, well, they seem to be supportive with the strategies that George laid out. We are intending to apply the same also for our portfolio.
Okay. Great. Now in the last 10 minutes here, I want to talk a little bit more specifically about some of your individual programs. I guess we'll start with COMP360 just because we've been talking a little bit more about that extensively. Obviously, you've got your phase II B study that's ongoing right now, data by the end of the year. Can you walk us through, George, kind of how we should think about the magnitude of the treatment effect at week three, the potential for a dose response, and how we should think about durability just because that is a pretty active investor debate after Sage had their data earlier this year in MDD. I've been getting a lot of questions about that. I guess specifically, what would you view as a win at both kind of the 3-week and the 12-week time points?
That we have separation across doses, that there are a population that we can identify who will respond and maintain that response, that it will be different across this. We have a 3-week endpoint looking at a 50% reduction in symptoms. And we're interested, can we hit that with 25? What does it look like with 10 relative to 1? So we're comparing a 25 mg dose to 1. We're then comparing a 10 mg dose to 1, looking for what is the safest, most tolerable dose. This is to inform our phase III design. The purpose for us is to create the most robust, which we have done, data set on the planet with regard to controlled studies for these medicines, both with healthy volunteers and now with patient populations, TRD, but other things we're working on. Our real goal is to inform our phase III program.
I'd be speculating, and I don't want to have other people's speculation based on my speculation of what we're going to look at. Obviously, we've seen in the smaller studies very significant differences. How that translates based on your other questions is we have to take that with a grain of salt. I think some of this is patients. I do want to clarify that this is not an ongoing study. We recruited 216 patients with the target three arms of 72. We exceeded that through the midst of COVID, actually. 233 patients were participating in this study. Last patient received psilocybin administration on the 8th of July. We have a 12-week follow-up and some data analysis to do. We are well on track for reporting later this year.
Absolutely. Okay. I guess just in terms of kind of going back to kind of the durability question, is there a specific, I guess, threshold that you're looking to meet on durability or that you've received kind of from your regulatory discussions?
From a regulatory perspective, remember, we're doing a single dose, a single dose of something of people who've been taken off of medication. We're looking at, will that single experience translate into 3 and then 12 weeks and for whom? If we have something that will actually do that with a significant number of responders, that's never, ever been seen in the past. What we do know from prior studies is that there is heterogeneity in the durability. What we don't know is how the heterogeneity in the initial patient population led to the heterogeneity in the durability. We spent a lot of time working on eliminating as much heterogeneity in the sample as we possibly can with referral, patients who come in with validated medical records for past failures, etc. I think we're going to see a lot of that.
What we see in durability is a large number of patients make it 3 weeks-5 weeks. Some decline after that. In Robin Carhart-Harris's study, which was the basis of our FDA Breakthrough Therapy Designation, what we saw was that at even 12 months for patients who had an average of 18 and a half years of prior depressive and 4.6 prior failures, approximately 25% of those folks had no longer any pharmaco or psychotherapy at 12 months, self-reported, and that the durability for many of them went at least to 12 weeks through the study. We are quite positive. I think the real issue here is who has the more durable experiences and how can we predict and how can we preempt relapse? That is really the focus so that we can help people get better and stay better.
Absolutely. No, that makes sense. Okay. I just want to save some time to ask Florian some questions too.
Please.
Sure. I guess, Lauren, just obviously, you have a very large portfolio of psychedelics and non-psychedelic drugs as well. I guess just thinking broadly about the portfolio, what would you say is, in your view, the most exciting program and why?
Other than Compass?
I was about to say. I was about to say. Sorry, I was still on mute. I was about to say, yeah. No, of course. I mean, with Compass, and it is also the most imminent one, of course, still this year, which will have—and I think George mentioned that or you mentioned that before—it will really have a great impact on the mental health industry, I would say, writ large, right? This is going to be very informative for all of us. We are looking towards those results and this data readout with great excitement. Next to Compass, we have—it is always difficult to pick your favorite child, but given that we have 11 programs. Ultimately, I think we are well diversified, and we are having a quite advanced program for each anxiety, addiction, and depression. With Arketamin, where we develop a program as a rapid-acting antidepressant for at-home use.
I think that's key here because it could circumvent kind of the scalability question that often arises in psychedelic-assisted therapies. We would have here something that is rapid-acting and potentially deployable at home. We now have to generate the data to actually prove that is true. We believe on the preclinical data as well as clinical data that, given the lower dissociation that you see in Arcetamin versus Esketamine, we have a good therapeutic index where we believe, where we have reason to believe, again, based on all the data, that we can develop the target product profile is suitable for at-home use. Very excited about this program. In addition, in the anxiety space, developing with GABA Therapeutics, the deuterated version of Etifoxine. Etifoxine, again, there's also a lot of prior evidence that shows that we can potentially develop a safer benzodiazepine.
I think we believe still that many of those available therapies also for anxiety. Benzos have clear drawbacks with a safety profile, addictive properties. If we could make a leap forward here for patients by offering them a safer version of a benzodiazepine, I think that is very exciting. In addition to that, in the addiction space, with DemeRx developing Ibogaine therapy, we would have another shot at a potentially disease-modifying compound that also, and we mentioned durability of effect, has a very, very durable effect when it comes to addiction patients. Very excited about those ones. Not meaning that we're less excited about the other ones, but these are just the more advanced ones in our pipeline that are closest to be in phase II or beyond, or yeah, about to be in phase II or in phase III.
Got it. I guess just a general question then on your portfolio strategy. I know you do have also, in addition to the Compass readout, right, there is also a phase II readout for RL-007 later this year. I guess can you just walk us through kind of how you are thinking about the go, no-go decisions kind of within the broader portfolio, not necessarily related to RL-007 specifically, but just the broader portfolio, and then I guess also related to RL-007?
Yeah. I mean, the common denominator of our approach to de-risk kind of the programs is on an asset level, look at prior evidence in humans. Here in the case of RL-007, and that's very consistent with all the other compounds, we have a good understanding of the safety profile of the compound. It has been in humans. It has been in phase I studies. We have also here strong signals on efficacy. Not only anecdotal evidence, we actually have biomarker data that points to pro-cognitive effects of this compound. That's what we're basically now trying to replicate, those pro-cognitive effects based on biomarkers, e.g., for instance, to then show that in the patient population of schizophrenics, we can replicate that. Basically to address cognitive impairment in schizophrenia.
That approach, deploying biomarkers as part of the clinical development plan to have, I would say, kind of micro milestones on the way to proof of concept, is our approach then to not only just say, "Here, you have $20 million, $30 million, $25 million," and get us to POC, but in a very challenged milestone-based way, deploy the capital and get it to work in those programs. That is kind of generally how we think about structuring trials and deploying capital to de-risk and also enable us to, you mentioned go, no-go decisions, to be really truth-seeking versus success-seeking.
I think that's also a benefit from this portfolio approach, that we are able to say, if we don't see the signals, then to reallocate funds that we earmarked for that program to other funds where we believe, based on data, that they have a better ROI and a better likelihood for patients to get approved medicines to the market.
Absolutely. No, that makes sense. Awesome. I think we're actually out of time. I just wanted to thank you both for taking the time to chat with me today. It's been very insightful. It's been great having you. I definitely look forward to staying in touch, especially ahead of the Compass data or the COMP360 data later this year.
Thanks so much, Nina.
Thank you, Nina.
Thanks, guys.