 All right. Good morning everybody. Thank you so much for joining us My name is Kate and I'll be here to lead this discussion. I'm just gonna move that slightly Maybe we could start With some introductions, would you'd like to start a cat arena? So thank you very much for inviting me. My name is the Katerina Malievskay I'm a co-founder and former chief innovation officer of company called compass pathways the the company is focusing on accelerating patients access to innovation evidence-based innovation in mental health and the leading program is developing psychedelics for Treatment resistant depression and other conditions of significant unmet need Thanks guys. Hi everyone I'm Cosmo. I'm the CEO of another psychedelic drug development company called spectly sci-tech It actually has a very similar mission to what a cat arena just said So it's it's developing psychedelics into licensed pharmaceutical medicines to help treat conditions such as treatment resistant depression and alcohol use disorder and we're looking at kind of short duration psychedelics like five MEO DMT Great, maybe you could both tell us a little bit about how you got started in the field So I'm a physician. I was trained in internal medicine and for many years I was practicing completely oblivious to What's actually going on in the mental health care space? I wrote a lot of prescriptions for antidepressants, but never really Understood what happens to patients when they cross over to purely mental health care space and when our Family became on the receiving end of mental health care My son developed severe depression and OCD and I was trying to find help for him I found it to be probably the most challenging thing I had to do in my professional life Completely against all my expectations. So that led us to think about how to actually bring mental health care to the level of evidence-based practice and efficacy and acceptable side-effect profiles Comparable to traditional medicine mainstream medicine But also we were very aware that it hasn't been any meaningful innovation in Psychiatry in terms of second from ecological treatments and even psychological treatments And the treatments are barely effective And the treatments have tone of side effects So the we started the company. It was an involuntary start-up So we kind of didn't have a choice after we've seen the What's the you know the experience that we had And we always thought of ourselves as a mental health care company to have to have a little more holistic approach to the development of psychedelics and we have chosen psychedelics not for Necessary for the love of drugs and not with a mission to help society enlightened or let's all take psychedelics But actually as because the early studies show such promising signals Signals that haven't been seen in psychiatry At all if ever We Thought we would explore whether there is a there where that we can you know take this compounds through regular Clinical development and develop it into a medicine that would be available and integrated into the National Care Guidelines Reimbursed and accessible to everyone So that was our story Amazing. Thank you. Great. Yeah, and Our stories kind of overlap and intertwine to some extent, so I Guess my story Starts with my mother who is actually one of the kind of most well-known pioneers of psychedelic science And she's called Amanda Fielding and she's been running a non-profit for about 25 years called the Betsy Foundation and and basically that the focus of that was it was set up in the 90s when there was a Real kind of it was like the dark ages of research when it came to psychedelics and and her Mission was to kind of Reignite scientific research into psychedelics and how they work in the brain and how they can be used to help people and because basically She and I think we all felt that these drugs were being ignored because of social stigma rather than good scientific reasons and so Beckley Foundation was one of a very very small group of of kind of institutes that were trying to support researchers who who wanted to look at this area and so in the 20 or so years they they were involved in a lot of the kind of most seminal research So some of the research the Caterina was just talking about it the in academic setting So small academic centers like Imperial College and Johns Hopkins and NYU started doing amazing research and And so then what happened after that was then suddenly there was enough evidence to say okay Let's move to the next stage which is move take this data out of the kind of academic center and move into a kind of fully Fledged drug development program where we can not just do interesting science But actually make these medicines available legally available through the regulatory system as Proper mainstream medicine so that that's kind of why we set up Beckley sci-tech to kind of move to the next chapter and Compass what the Caterina did was started before us. So we've kind of been working in in similar kind of areas anyway Can you tell me a little bit about what have been the most successful? Treatments in terms of pervasive conditions or drug condition. Sorry drug resistance mental health conditions Within psychedelics So I mean well, I mean please the so I'd say that the in terms of regulatory stages the the furthest ahead is MDMA for post-traumatic stress disorder, so that's MDMA in conjunction with psychological support for for treating people with post-traumatic stress disorder and and that's a nonprofit slash benefit corp have been running it called maps and They've been around for a very very long time as well and and they've completed their phase three So in clinical development, you know, it goes pre-clinical first You have to show it in pre-clinical models. Then you go into healthy volunteers. That's phase one phase two is showing in in some Patients that it's safe and effective and then phase three is the large Patient population where you show it safe and effective and they've completed phase three And so hopefully are on track to actually get that approved by the FDA within the next year or so year or two and then Coming up close behind when I'll pass over to Katerina because really it's what compass are doing Well, we will see it's a marathon, right? We'll see how long it will all take So we have cell seven day develop clinical development program Come 360 which is the synthetic proprietor synthetic formulation of Cell cybern that we finished face-to-be study a dose finding study that showed actually for the field of psychiatry remarkable results In the highest dose that was well-tolerated 37% of people responded or remitted after just one administration and 29% of them maintain response in remission three months later. So that is a paradigm shift for treatment and psychiatry But it's not only just pharmacological effects of it, but it's also Incredibly empowering for patients. They I think the the value that patients see in this approach is that They feel that there is a sense of agency there is a sense of self-efficacy that they can separate themselves from the symptoms of depression and that's that is a very powerful realization and Insight that they gained during this treatment. So that's our program and then of course, there are a number of other companies that are Developing, you know a variety of psychedelics and cosmos company is just one of them a very interesting compound Do you want to talk about that? Yeah, I mean and maybe it's worth giving just the context of how Psycho psychedelics are being kind of used as treatment. So I think just to clarify it's you know it's being delivered in conjunction with Psychological support and and basically the way it works is If you're a patient, you'll first kind of meet up with the therapist and get what's called Preparation therapy. So it's basically preparing you for the experience kind of and Preparing you to think about what you're trying to get out of the experience then you go to a clinic where the drug is administered While being supervised by the therapists in the room So it is you know under close supervision and then subsequently they're given what's called integration Therapy which is to kind of process the experience and use it for kind of long-term behavioral change, right? So so that's kind of basically the way the treatments are working broadly speaking now broadly speaking and And the different compounds can be dropped in there Depending on the different indications the different kind of conditions that are being treated, etc So the the condition that the drug that we're looking at primarily is a drug called five MEO DMT Which is it's interesting because it's known to be very very potent, but also very short in duration. So drugs like Oral MDMA and oral psilocybin and LSD to some extent they've had by far the most research done on them Historically, so they're the most well characterized drugs There's the most data on their safety and their efficacy in a range of different drugs and and you know certainly I expect MDMA and psilocybin to be the first drugs that become approved But then there are these other psychedelics like five MEO DMT, which are much less Researched so far, but they have some very interesting characteristics. So the idea with five MEO DMT is because it's so short in duration The hope is that people spend less time in the clinic and therefore potentially it can be kind of a more cost-effective treatment all of this is to be Born out in the research. So we're we're earlier stage But there's there's a lot to be kind of that and there are lots of other interesting compounds and then analogues that are being developed Completely new unique psychedelic compounds that are being developed as well exciting stuff and how long does the I Guess the benefits last so far in the research Well, that's a very good question. And I think that well one of the things that we were talking about before as I think there's There's a bit of a danger with psychedelics where they attract Sensational headlines whether it's good or bad. I think and and so there can be a sense and at the moment We're in a wave of positive news around psychedelics. Obviously Previously there's been a wave of very negative news back in the 60s, etc and I think there is there's been some amazing data where you People have been given a single dose of psychedelics and they've recovered for a whole year or you know indefinitely from Depression or whatever it is. I think I think companies like ours are trying to kind of temper expectations You know, it's not a miracle cure for everyone kind of thing but it hopefully is effective and durably effective for a Significant period of time. So I think well your your study you can talk about but it was you know We're seeing results for three a single dose can have durable effects for three months at least kind of thing, which is pretty amazing, I would just say that despite the encouraging results, I would say do not try it at home because I Think not everyone responds. It is definitely not a miracle drug and we still don't know who is more likely to respond who is more likely to respond adversely and Anything that can help you can hurt you and so we still The way I think the psychedelic industry if you always sector psychedelic sector approaches it. I think is very Sensible that we are systematically challenging the assumptions that were made in the 50s and 60s Do we need to have two therapists? Do we need to have extensive? preparation and integration how much patients really do need and those are all Empirical questions that could be answered in the research So we can select and support patients in the best way possible and optimize the outcomes so that I think is the You know the goal and the future and so the therapy optimization, I think You know maybe that the drugs themselves are not even so innovative But the therapy optimization research is a cutting edge and the most interesting part of it and I think right one of the big questions for the whole field is You know how many doses at what interval are going to be required to? Not just get someone well, but keep someone well because conditions like depression. They're Traditionally a chronic depression. So, you know, there are waves of depression that people suffer and the question is We're characterizing at the moment what a single dose does and how long it can last but I think a secondary question a very important one is Okay, say a single dose can get someone out of their symptoms and get them into remission How long does that last or at what point does that person one second is it as their relapse? So those are the things that the the field needs to discover but that requires a lot more research Absolutely, and how do you recruit people and what is the eligibility for that? Well There are different ways of recruiting patients for studies I think patients Patients and psychiatrists and care health care providers have now much more informed about all the research that is going on in psychedelics on all the trials that are going on psychedelics and so Patients can reach out proactively or they can be referred by a health care provider and so that requires a lot of education of Physicians who would refer a therapist who would refer patients, but also I think a lot of kind of balanced conversations in the media because Patients might want might come with unrealistic expectations. You know, those are the patients who's who's suffering for decades And nothing works. No available treatments work for them so they oftentimes see it as a last resort and They literally say I'm here to be cured and it may may not happen So I think more balanced conversations about potential of psychedelics is is really really important and When we talk about mental health, we know it's an area that's been traditionally Short-funded in the public health system particularly. How do you see this? I guess playing out in a more public inclusive health sector in Mental health in general or particularly psychedelics. Yeah Well, I think psychedelics You know because they are scheduled substances By definition the schedule one means that they don't have Medical benefits and they have high potential for abuse none of which is true and I think the signs the existing evidence now Showed very clearly that psychedelics have medical potential So Increasingly government for agency started funding research in psychedelics. They Swiss government funded research Large study of psilocybin in depression German government funded the Another trial in Germany and an AMH and NIDA in the US started funding psychedelic research So there is a little bit of a movement on that and also MHRA in the UK. Not a major at nice NHR Started funding psychedelic research, but in general of course mental health is such a complex Area that it requires really, you know thoughtful and harmonized approach to funding because there are different parts. It's an ecosystem of You know elements that don't have commercial Viability that only can be developed as nonprofits and then there is There are parts that are clearly businesses that like drug development clinical development And so all these parts need to work together in harmony and that is the challenge of the funding Maybe Just to clarify one of the things that what we're both trying to do in terms of making these drugs available is It's not about drug policy reform What we're trying to do is take the drugs through the classic pharmaceutical drug development approach And if you can show that your specific formulation of a specific psychedelic drug When delivered in a specific way is not only safe, but effective at treating a condition like depression Then the regulators like the MH like the MHRA in the UK or the FDA in the US then they basically have to like agree that that is a prescribable medicine, so there's There there'll be a change of scheduling for that drug, but there's not it's not a big political Drug policy question. It is a kind of scientific medical question that can this drug be prescribed And once it can be prescribed then the question is where and how is it prescribed and I think Compass have been doing a lot of work on that as they're kind of close to the market But I think generally speaking the expectation is that there will be kind of specialist interventional psychiatry centers basically where People go to have Psychiatric interventions whether that's so there's a drug called spravato at the moment Which is already out on the market. That's as ketamine so it's Johnson and Johnson developed it and it is a kind of ketamine Analog that's been approved for treatment resistant depression So that's already out there now, and that's actually on track to become a quite successful Drug for treatment resistant depression and so that's kind of laying the the groundwork for where these Drugs can be administered again. It has to be delivered under supervision in particular centers with particular training And I think as more drugs become available They'll be increasing numbers of these centers and they'll be increasingly kind of spread across the world And I guess related to that. What does training look like? I mean, I imagine there's a whole group of Psychiatrists coming out of training now looking for the future. Well, is this already embedded in Medical training or is it something that will be introduced? How how will it manifest? Yeah, I think in order to do large-scale late-stage clinical trials We had to train a lot of therapists and we had to educate a lot of health care providers In what to expect what patients are suitable what patients are not suitable. So over the period of six years that our company exists I think we've been in interactions with a lot of health care providers and we've trained Over 300 therapists already and so all this capacity building in the in the in the system will translate into more and more training and more You know as we gear towards launch post approval It will still be You know, we will still continue learning how to train You know what the best approach is so it will be an ongoing process, but I think we have they the basics down Yeah, and I think exactly at the moment again, this is one of the interesting things for the industry I think if we look into the future I think we expect this to be a class a new class of medicine for mental health and there'll be Multiple compounds that will be available and at the moment each company is having to train therapists specifically to their compound to be able to deliver their compound for the which is In when you look into the future that is not very efficient So there are multiple therapists who have had to gone through our training as well as compasses training as well as maps for MDMA Training, which is a lot of training and there's a lot of overlap So, you know in the future, hopefully there'll be some more kind of Standardized system which makes it kind of easier to train the scale and number of people that we we need to train And a question I didn't ask earlier. I know you mentioned nasal sprays in both of your trials How are you administering the treatment? So one ours is ours is intranasal So it's the drug that we've developed Five MEO DMT is actually if you take it orally, it's not kind of bio available So it needs to be delivered But kind of it needs to avoid the first-past metabolism and so intranasal is a kind of well-established Roots of administration for For delivering those kinds of drugs. So we're yeah, we're delivering it intranasally, but I think We formulated it as a capsule so patients take a capsule and you know that day of administration looks like the patients come into the clinic Go into the non-clinical the room that we you know turn into sort of non-clinical environment non-stimulating various soothing colors And patients take the capsule And lie down on the couch put on the eye shades and listen to specially designed Music playlist that sort of follows the pharmacokinetic of the drug And that experience lasts about About four to six hours and the therapist is always with a patient in the room To support if anything if patient needs anything But that's that's a normal formulation and that's how the experience looks like and that's What a Katerina is saying there is also I think important for for kind of psychedelics like psilocybin and five MEO DMT I think What people sometimes don't understand is they think oh you're in a room with a therapist for the whole duration of That psychedelic experience You just kind of chat having a therapy session a kind of talk therapy session and generally speaking certainly with both of our drugs Actually that what the patient is prepared and encouraged to do is to actually kind of close their eyes and kind of look Introspectively and go through their own personal experience. It's not a kind of psychotherapy chat That the the therapist in the room is there to make them feel safe and make them feel if they do need support Make them feel safe and make them feel comfortable Going back into the experience and kind of surrendering to the experience rather than having a big chat if you see what I mean Okay, and let's talk a little bit about the future. I mean, I know with Healthcare in general there's a lot more of a trend towards Digital digital first telemedicine things like that remote settings. Do you see any of these things playing into the psychedelic therapies? Yeah, absolutely. I think that There are a lot of questions about scalability of the treatments because it's you know, it's Six to eight hours of the session plus preparation and integration. How can we? Make it more scalable without sacrificing safety and potentially even optimizing the outcomes. So all this research is ongoing. We are looking at For example The predictor we're looking at large language models We're using large language models to analyze patients narratives before during and after to understand the potential predictors of adverse events or potential predictors of Better clinical outcomes. We're also learning how to support patients better based on the What they've identified in preparation so in and make that More efficient and increasing patient safety. So there are many technological sort of add-ons that we could Deploy together with psychedelics. Yeah, and I mean I completely agree and I think Digitals, I think we both agree digital is going to play a really important role in making these medicines as scalable and affordable as possible and I think That there are a number of ways that they can play a part like a catering was saying firstly I mean the dream scenario is to be able to identify Which people are going to respond and not respond kind of predictively so that you can maximize the efficiency of the treatment firstly so you kind of Select the people who are going to respond best In addition, there's the kind of the easier thing is at least providing digital tools to help prepare patients And support patients afterwards and I think if you the way psychedelics seem to work is there's this kind of you know Psychological experience and there's also a kind of physiological Underpinning where we've seen in the brain that there's this kind of neuroplasticity. There's synaptogenesis. There's new Neurons being there's a lot going on in the brain anyway, but it creates this window of neuroplasticity which basically allows people to change their behavior in the long term and That this window is a potentially an amazing opportunity for digital Interventions to come in and actually be more effective than if they were just being given to someone who hadn't had a psychedelic treatment So there's a lot of potential synergy between the kind of digital therapeutics and the kind of pharmacotherapy of Psychedelics and there is also I think one caveat with psychedelics. This is not everyday medication This is one off and then there is a period of time when patients maintain response or remission but at some point some of them will start deteriorating and if we can follow this patients prospectively and Understand when they start sliding back into depression and treat them more preventatively avoiding that sort of ups and downs that predict they undesirable course of depression that would you know digital phenotyping would be super helpful in managing this patients great I think we've done all we can do today time-wise although I think we could have spoken for another hour frankly such a great topic Probably. Thank you so much for joining me. Thank you. Thank you. Thank you