Transcript
Speaker: Welcome to the Healthcare Theory Podcast. I'm your host, Nikhil Reddy, and every week we interview the entrepreneurs and thought leaders behind the future of healthcare care to see what's gone wrong with our system and how we can fix it.
Speaker: Today's guest is Dr. Michael Gold, the Chief Research and Development Officer at Compass Pathways. And Mike is a neurologist by training, and the reason I'm so excited for this episode is that he started his career in academic medicine, running a memory disorders clinic for Alzheimer's, and then he moved into the drug the drug industry ever since.
Speaker: He worked at almost every single corner from Big Pharma, at BMS, Johnson & Johnson, GSK, AbbVie, multiple small biotechs, large CROs, alongside the FDA itself, and across nearly 30 years, he's worked across every brain disease you can think of, from every angle you can think of, and today's leading at Compass Pathways, which is developing Comp360, a synthetic form of psilocybin,
Speaker: the same active compound in magic mushrooms, but for treatment-resistant depression. They're now a billion multi-billion dollar company and are in two positive phase two trials and are finishing up their FDA application and could be the first psychedelic medicine approved in the United States. So episode ends up being a great discussion across the different pathways going on in biotechnology and neuroscience.
Speaker: Hi, Dr. Gola. Thank you so much for coming on The Healthcare care Theory. It's great to have you. Oh, it's a pleasure. Thank you for inviting me. Of course. And before we get into your actual work, I think it would be good if we got to know you a little better. I mean, you started um as a doctor at South Florida College of Medicine, and you ended up leaving academic medicine after a few years to join Bristol Myers Squibb and spent your career there ever since. But I would love for you to fill in that gap from being in in academic medicine to end up going to work at a big pharma company now staying there for so many years.
Speaker: Maybe like at that time as a doctor, like what grew you interested in this world of like clinical trials and research and things like that? Like, could you fill in those blanks for us, please? Sure. Be my pleasure. So so look, I i trained as a behavioral neurologist and, ah you know, my Uh, my path was really clear as ah as a, kid and adult, I was going to be, uh, in academic medicine. I love taking care of patients. I love clinical care.
Speaker: Um, I ended up ah working at the university of South Florida for a bunch of years running a memory disorder of clinic. And, you know, when you're in, in South Florida, you're at the sort of epicenter of chronic aging. And, you know, our population was on average 10 years older than the rest of the country.
Speaker: And so we were drowning in Alzheimer's disease and Parkinson's and all these age-related neuro neurodegenerative disorders. And, you know, part of me was really kind of fascinated because i I got to indulge as a behavioral neurologist and things that were of interest to me, language, praxis, executive function, you know, how semantics breaks down over time, et cetera, et cetera.
Speaker: But you know first and foremost, I'm a physician and in my calling was to alleviate patient suffering. And I find myself really very hampered and unable to do much for my patients. And we have the first generation of treatments for Alzheimer's disease, you know these cholinesterases,
Speaker: were very modestly effective, but they didn't slow down disease progression. And so you started to feel, at least personally, I started to feel very frustrated that I had nothing really better to offer my patients. And in other areas of neurology, migraine, epilepsy, MS, there tremendous advances.
Speaker: um And so after you know doing that for a bunch of years, there was an opportunity to actually, i got involved in clinical trials. I you know was involved in a bunch of different studies and it kind of clicked in my head, you know, this this is really an important thing to be able to do, which is to do these clinical trials, to do them really, really well, to get, you know, high quality data, because this is sort of the way we answer the research question, does this actually work or not, right? And so I got very interested in in the clinical trials. and
Speaker: you know, as a behavioral neurologist, we're always kind of trained in in sort of, you know, very complex study methodology, mostly N of ones, you know, ABA designs, et cetera, et cetera.
Speaker: But a lot of what I studied as a behavioral neurologist in terms of cognition directly translated to what I was seeing in clinical trials on Alzheimer's disease. And then there came an opportunity to actually go work on a very early stage compound at Bristol-Myers Squibb, and it was a gamma secretase inhibitor.
Speaker: And for your audience, you know if if they if they don't know, this is a mechanism that could have been the first disease modifier for Alzheimer's disease. Gamma secretase one of the enzymes that cleaves the APP molecule into beta amyloid.
Speaker: which is supposed to be the toxic agent for for for Alzheimer's disease. So for me, it was you know like, you know let's go. And it was a great opportunity to go into industry at the early stages of development because I wanted to actually see the sausage making and the actual mechanics of early development, the clinical pharmacology, et cetera, et cetera.
Speaker: So I spent a couple of years at BMS, about three years, and then moved to other companies. And over time, I've moved to a variety of different companies, some very large and some very small. um primarily in pursuit of interesting compounds and in interesting pipelines that would allow me to develop novel medications.
Speaker: You know, my first love had always been neurodegenerative disorders, but as you spend more and more time in neuroscience, you start to respect the fact that there is huge unmet medical need brain and in epilepsy and God knows in psychiatry, depression and schizophrenia and alcohol abuse. So, you know, misery knows no boundaries in this sense. And so one of the things that you start to appreciate is that when you're working in neuroscience in terms of drug development,
Speaker: that there are opportunities to do good in many areas, you know, and so that's sort of what's been driving my interest in different companies, different pipelines, different methods or different kind of methodologies, but also different therapeutic approaches.
Speaker: Yeah, it's interesting to me because I think in a lot of different industries, you can really like your impact can like change in many different ways. For example, as a doctor, your impact is very much like NF50. Like there's like may have like a certain amount of patients impact very, very strongly. um But not working on the operational side, like you're able to do that, but you can also impact many, many, many more people like a smaller lens because you're not actually talking to them every day, but like you're getting to them a drug that will like impact maybe thousands of people's lives and at the larger level, maybe millions. And I think that's very ah alluring in some ways.
Speaker: um But At BMS, I'm curious, I mean, you're now at this large company and you can actually see like all of these different variables. i mean, the cost, you have competition, you have like trying to get into sites, you have all these different trials and like you're running in different sites and kind of get them together. i know it was like an earlier stage trial, but like what actually when you first got into that company, like what actually surprised to you about that? Was it kind of what you expected? Was it drastically different from your expectations as a clinician? So, so let me just kind of set set the record straight. i I was at BMS for about three years, so I was not there for a very long time and then moved to other companies, but across the various companies that I've been on, but let me, let me kind of give you more general answer.
Speaker: So I, I think, you know, different companies have different cultures, but what I found to be generally, you know, a common theme is, you know,
Speaker: There are really good people working in these companies, very dedicated physicians, very dedicated scientists. you know um you know Pharma doesn't have the best of reputations, but I can tell you that I've been incredibly lucky to work some really, really good, dedicated people who just from the heart want to do the right thing. We are very clearly focused on the need to get new treatments to patients.
Speaker: Many of us are directly affected by the disorders that we're trying to treat our families are so it's not a it's not a hypothetical or abstract for many people. It's very concrete, right? People's parents, kids, spouses, friends, you know, so it it becomes intensely personal in many ways.
Speaker: I think that what what I what I saw was kind of this this rigor for good science right show me the data don't spin it don't massage it you know it's it's a you know these companies are populated by smart people good scientists they can look at data interpret it so you don't have to do in fact it actually works against you to try to spin and you know we we weave a story around it good storytelling is really important regardless of where you are because you need to take people on a journey
Speaker: But what I found was a real kind of sense of it has to be good data. We we want to make sure we're doing high quality science. Part of it is because you're actually taking money that could have could go to something else and spending it on money.
Speaker: let's say a product for for depression or a product for for for whatever it is. And if it's not high quality science, you're wasting resources, you're wasting time. You're actually disrespecting the patients who come into our trials and give us their time and and and take risks by being in our studies if it's not good science. And and I think across the board, I've been very, very favorably impressed and I've been very lucky to deal with companies whose leadership understood that from the start.
Speaker: Yeah, that I think it's good to have the like data first culture because i mean, it makes sense. You have like a certain size of your balance sheet. you can only allocate to a certain amount of different companies and assets and drugs. Like it would be great to explore everything, but that's just not the reality of what happens. But I mean, at this time, I mean,
Speaker: GSK, Johnson & Johnson, BMS, like these are big companies, like a lot of money, but still, yes, limited and constrained resources. Well, I mean, let let's let's also be clear, you know, just because they're big companies doesn't mean there's endless buckets of money. So, yeah. And, and you know, folks are listening to should realize, you know, companies like J&J or AbbVie or GSK, there's a portfolio. They're working in multiple therapeutic areas, immunology, oncology, cardiovascular, neuroscience.
Speaker: and And there is a competition for internal resources. And that is that is where you have to really think about, okay, you know where do I put the seed corn? Some of it I have to put into things that are gonna yield results sooner rather than later.
Speaker: you know, the riskier stuff can have an outsized ah impact. So that's part of, you know, where neuroscience sits. Generally speaking, we are one of the riskier areas because we're dealing in areas that are not as well understood and not as easy to work in compared to, let's say, infectious diseases or or or cardiovascular or metabolic. And, you know, I have all the respect for people working in those areas, but the the animal models, the pharmacology, the genetics,
Speaker: in some ways, much easier in other areas than in neuroscience. I mean, you know, psychiatry has a standout for an area where we still don't have a good understanding basic molecular mechanisms. Yeah, that makes sense. I think Yeah, it's it's it's I think it's a really interesting point. um When you have like a trillion dollar company, like it doesn't really mean they have a trillion dollars to spend, obviously. And even if they did, they would have to divide that up between different therapeutic areas and even then different phases. Like you need a broad portfolio for this whole business model to even make sense in the first place.
Speaker: But i mean, part of that is also just when you pick an asset and it's going through phase one trials, looks good. Phase two gets a little bit murky. You can't just always keep funding the drug all the way through. so I think part of your job at big pharma is also to understand like when to cut things. Like when do you realize like some assets you have to walk away?
Speaker: How do you decide to double down? Like, is that a big part of your decision there? What did that look like? Yeah, I mean, it it again, it cuts across both big and small pharma. I mean, if you're a single asset biotech company and it doesn't work,
Speaker: you you got to cut your losses and move on, right? I mean, but I work on one company where, you know, the asset just failed and we had to liquidate the company. So it's not ah it's not a big pharma thing only.
Speaker: in In the context of, you know, what happens as you move from earlier stages to later stages and you get more, you know, the signals start to kind of come out. Maybe they don't come out as clearly as you hope, right?
Speaker: that's That's where you move from the science to the art of drug development. In the sense of, you know, when you do the early stage development, your dose ranging and it's just, you know, pharmacokinetics, some degree of target engagement, you know, that sits in kind of one bucket of certainty and confidence.
Speaker: You start to get into more clinical things. And in particular, again, in neuroscience, where many of the outcome measures are subjectively reported, right? There's there's objective stuff. Somebody had a seizure or a stroke, you know, there's some things where it's very objective.
Speaker: But take, for example, pain. You know, pain is a subjective experience. And what you may describe as a 10 out of 10, you know, if I were to experience what you're experiencing, I might say it's a four out of 10. And so when you get into those kind of more heterogeneous populations or more subjective outcome measures, then you have to start to think about, you know, how do how do I actually manage that? And how do I design studies that can deal with that and still provide actionable clear data, right? So that's, there's there's a lot that's going on during, you asked about that. This is where a lot of kind of imaging, physiology, digital digital sensors, wearables are being brought to the table to help objectify behavior.
Speaker: Yeah, I feel like a lot of it maybe is about like asking the right questions. Like if you ask too many questions at once, you get too many data cuts, like it's equally hard to analyze all of that maybe, or how do you highly feel about that? yeah yeah like so you you you You put your finger on a really interesting dilemma, which is, um we talk about the kiss principle that keep it simple, stupid, right. Which is focused on, ah on the, on the research question. It's, you know, that's kind of like, that's all well and good.
Speaker: you know But when you have resources to only do one phase two study, you don't have the luxury to do two or three of them, there's a tendency to pile on and say, well, let's talk about this we need ask about that and it's only five minutes for this and it's only 10 minutes for that. And you start to add on and and and aggregate you know a lot of additional outcome measures And the problem is you know you can't predict where you're gonna get. Sometimes those outcome measures line up and it's beautiful, other times they don't, and it becomes confusing in terms of what are what are you actually looking at?
Speaker: So this is this is you know this is really kind of the art of of clinical development. It's a conversation with your stakeholders. What's really critical, right? What do you really need?
Speaker: what are What are critical data for go-no-go decisions? What can you add on later? you know, um how much confidence do you have in in in the in the instruments that you're using? You know, what is your psychometric construct?
Speaker: What is your validity? You know, are there ways of getting data that are sort of confirmatory coming up from other angles? How much do you do in a clinical trial? How much do you extract from, you know, claims made databases or real world databases, et cetera? So there's a lot that goes into thinking about with the kind of studies, particularly early or translational studies,
Speaker: There's a lot that goes into thinking about, you know, what is the minimum package? and And, you know, then you do you add anything more around? Because for every instrument that you add, it's more time, it's more cost, it's more risk, it's more kind of burden on participants or patients. And, you know, if a lot of these folks at a certain point, they walk because it's just, you know, it's too burdensome.
Speaker: Yeah, I've read that I think most of large percentage of clinicians who are becoming investigator don't do it again. Similar thing a lot of patients like you don't fill enrollment. I think this idea you want clinical trials to be as engaging and easy as possible for people both on the clinician side, but the also the investigator of the investigator side, also the patient side is really important. I mean, where did you see and I think it's like an interesting point because when you think about clinical trials, there's billions of dollars oftentimes being spent, sometimes usually hundreds of millions. um You have like hundreds of patients, you have the best scientists looking at certain assets, yet things like still get really far along and fail, like Alzheimer's specifically.
Speaker: um i think at the time, like Eli Lilly, like, um Pfizer all had like assets in like the early 2010s that didn't end up working out. yeah And I think it's confusing to a lot of people because they're thinking like hundreds of millions are being spent.
Speaker: We have the smartest people. um like Why is this not working? We've been studying this for seven years. And I mean, for you, I'm sure the answer is clear, but would great to get that perspective almost. like You have more data than ever. we have more resources than ever, but it's not necessarily easier to do to get a biotech out to market or to get it through clinical trials yeah what do you think is really the constraint there it's it's a naive notion to think that just because you throw money at something it's gonna work right this is not this is not mechanical engineering this is not computer science where i'm building a widget and and i know exactly this is human biology at its best and worst okay it's you know particularly for psychiatry like i said there's no understanding molecular biology underneath it we have no idea
Speaker: what causes depression or schizophrenia or bipolar. Genetics haven't yielded anything. Autopsies, there's no observable pathology. There are models that suggest what's going wrong, but you you you can't ask a mouse whether it's hallucinating or it's hearing command delusions, right?
Speaker: So the the the models themselves are limiting. You can model very limited aspects for certain diseases. Let's take Alzheimer's disease, right? Everybody is enamored with transgenic models of Alzheimer's disease.
Speaker: They're great models for amyloid overproduction. They have virtually zero to do with the real disease. so part of the problem Part of the problem is translation. right You need better models, you need you know more realistic models.
Speaker: There are people that have built in silico models of the disease because the animal models are are impossible to do. You can't work in primates. and Even if you wanted to work in primates, you need to work in primates that 20 to 30 years old.
Speaker: It's both unethical and it's also impractical. right So a lot of the failures early on were, in my view, due to people buying too much into what the preclinical data were telling you.
Speaker: Okay. So there's a part of that.
Speaker: There's a quote from Einstein that I am absolutely in love with. He says, if we knew what we were doing, we wouldn't call it research. And so I think people have to understand that we're going into into areas where we don't have a really good understanding of exactly what's going wrong.
Speaker: And then we're dealing with folks who some of these disorders, whether it's a neurodegenerative disorder or a psychiatric disorder, These may have started in adolescence and we're getting people with symptoms 30 or 40 or 50 years later.
Speaker: You know, we may be carrying risk factors for depression since infancy, maybe epigenetic for all of them. Right. And so we're starting treatment when, when, when symptoms manifest, it's very difficult to do clinical trials for primary prevention other than vaccines.
Speaker: when the outcome is 15 years or 20 years after the intervention, right? So there are a lot of really interesting things that that make it that much more challenging and difficult for us to be able to do this work in neuroscience.
Speaker: um Yeah, I mean, the studies, I mean, solanuzumab is a great example. You talked about Lilly, right? I mean, i my hat's off to Lilly. It's a great company and and they stuck with it. But God knows they invest a lot of time and money in solanuzumab and it didn't work.
Speaker: But that's part of what's necessary is the kind of staying power to kind of stay committed to being in a particular area and not give up. I mean, they eventually got to where, where, where, where they got the Nanomab on the market. It's, you know, it, it's an effective drug, albeit modestly effective, but it's helping some people.
Speaker: Yeah, I mean, he even a small one's a win, right? Like, it's still important. And I think that's, and it's it's difficult because I mean, when other areas, I don't want to say like, cardiology and other disease areas are solved, they're not not even close to it. But like neuroscience on a relative basis is we're a lot further away from getting there. um In terms of understanding the disease biology of like, how does depression or especially Alzheimer's is probably the hardest case.
Speaker: quote From my perspective. So I would say that in that in that in that space, you know, look, we we always talked about, we wanted neuroscience to look like oncology is looking right. Precision neuroscience, get a specific diagnosis, interfering with a specific pathway, et cetera, et cetera.
Speaker: And I have to say, we've made huge, huge progress. I mean, look, let's, let's, let's, let's let's not forget where, where we come from. When I started, and when I was in training MS,
Speaker: very bad mean very bad i mean particularly primary ms right you were looking at people that you know we're going to be disabled wheelchair veg it's horrible horrible horrible look at where we are now right it's it's 20 30 years later but i can i can put ms or physicians can put ms to rest and no disease activity Think about where we are with, you know, Parkinson's or ALS and, and even in, even in psychiatry, I mean, you know, the kind of, the kind of benefits that we've seen with, you know, some of the typical antipsychotics, I mean, let's, let's not, let's not underplay the victories that we've had. I mean, I agree. There's a lot of room to go. There's still a lot of room to go, but sometimes our memory is a little bit short compared to where we were.
Speaker: Right. Yeah, i think i think it's us I think it's also that um'm not only that our memory is short, but I think it's also um you see like so much progress so often in other fields that you feel like, why isn't this happening? I assume you'd feel like, why isn't this happening in neuroscience? But I think recently there's been a lot of changes. um I mean, I think you've kind of characterized in a past interview that like neuroscience is a field that like swings between like optimism and disappointment. And I think that's like an interesting...
Speaker: um point. I mean, the back then, like, I i mean, recently the FDA has like given approval, i think, to Biogen's um aboutins a new asset. And then they had like, and then had controversies there, like Lycos had an issue, of course. But then we also had really, really good outcomes too recently, like blood tests are able to detect like Alzheimer's pathology a little better. There's better brain imaging. So we have like ups and downs, I guess, in neuroscience. I mean, how do you see? I mean, so it it oscillates, right? yeah If you have better diagnostics including you know all the pet imaging and the blood tests for for Alzheimer's disease, it invariably is going to help to improve the quality of clinical trials and target the populations in clinical trials. And this has been an issue, right? I mean, I was not not not in a pejorative way, but part of the reason that solanuzumab failed, and in this came as a post-hoc, was that a lot of the people that were enrolled in trials didn't have the right pathology. you know
Speaker: It kind of boggles the mind, but we didn't have the tools to actually able to do that. And if we had some of the tools, they didn't scale up there're not enough pet scanners and and and you know, cyclotron to be able to image as many people. So in some ways, better diagnostics is absolutely going to help us to zero in on making sure that we have the right population.
Speaker: And it's not just a diagnostic because these biomarkers also help us to measure rate of progression, right? They help us to measure response to treatment. So if I, if I have somebody, you know, again, i don't want it to be just about Alzheimer's disease,
Speaker: But there are other areas where you know we we have good markers for targeting agent response to treatment. um Look at MS or you can look at migraine, you can look at SMA, any number of places, right? That that helps in the in the sense that it gives hope, first of all, it gives hope to patients that we can make progress. B, it gives hope to people who are funding discovery that we're not really just beating head against the wall with something that is impossible.
Speaker: So when you said that small victories matter, absolutely they do. Right. Yeah, I agree. I think it's, I mean, I'm it's, it's also equally interesting. Cause I think like back when we, we talk about like, yeah, Lily and stuff like at that time, um, because neuroscience is so it's like part of the riskier portfolio when things got hard for biotech, it's like neuroscience got cut down, like pretty hard.
Speaker: And like GSK AstraZeneca cut back on a lot of their research. like Pfizer went further. And I think now we're seeing like that swing up and down. Like, I mean, how do you think we're in like a pendulum shift now on the way up? Or do you think this is like a sustainable future? that's nice look I think neuroscience goes, goes through pendular swings on ah on a, on about 10 year basis. Right. and I think, ten years yeah you know, I lived through the downsizing, you know I remember going through the decade of the brain. I still have my little, you know, plexiglass thing from Burroughs welcome decade of the brain. And then it was that decade of not the brain.
Speaker: yeah And part of it is kind of the same thing with with you know some of these, you know let's let's say, cycles of hype in reality. you know There was a lot of hype about where were going to It didn't pan out.
Speaker: Other areas became much more tractable and attractive. And I think neuroscience paid the price for a lot of the stuff that happened in oncology. Oncology became, you know, PD-L1s, et cetera, you know became became very attractive.
Speaker: My sense is that, you know, neuroscience as a whole right now is kind of bouncing back. I think it's two parts it, right? one One is what we've seen in terms of biomarkers and sort of, you know, novel approaches to hard to treat neurodegenerative disorders.
Speaker: And the other part, honestly, is the resurgence in psychiatry driven mostly by psychedelics. because out of a sudden we now have a new class that seems to be showing a lot of signals that it can actually help with really serious disorders and it's a class that we've known about for years so it's coming in already kind of gift wrapped with the fact that it's not really novel pharmacology but it's gift wrapped in the sense that we're actually doing the right kind of clinical trials to show that it works and for whom it works because it's not going to work everyone Yeah, that's that's interesting because I know we we talked to Alta Neuroscience last year and i think that's a huge part of what they're doing is trying to say, mean, we have this biology, but the issue is that there's no depression for everybody, as you know, like some people have theres certain types and you we don't even know how granular it really gets. So being going to get the right people in the trials and also understanding like not just like what is depression, but like what is this different variance and and ideally getting that narrowed down as possible as narrowed as possible. And I think Compass has a really really unique
Speaker: like world or play into all of this but before we get into compass i'm i'm curious i mean you had after gsk and your early time in pharma we're really talking about you had a really interesting story i mean you went from a small biotech to leading neurobiology at ucb and then you went to ppd which is more of a cro working across different assets um and then you went to big pharma at abby so it was really cool i mean you kind of had this whole um path from like From what I see, almost every type of company you can work in, it's like in the drug development world in about a decade.
Speaker: um I mean, turbulent time for neuroscience, but also really cool time for your career, which I think could be interesting. And maybe I'd love if you could like a lab, maybe provide some color. Like you were a physician before this, you worked in big pharma. um What was this time like? Like what drove you to shift through all of this? And like, what are your takeaways coming out of like all these different lens and hats you put on in the world of biotech? Yeah.
Speaker: Interesting. loaded Loaded question too. I mean, look, some of some of those decisions were based on family situation, right? And I'm not going to get into any detail, but I i made a commitment to try to provide my family a stable home and background and not moving around more than absolutely necessary.
Speaker: But i all have I also have to say that there was value in learning how different parts of the enterprise work, right? getting you UCB allowed me to get an understanding what a specialty pharma company looks like with a very narrow focus and very specific areas of interest, right?
Speaker: um And that was one one set of experiences. And then you're right, I spent time at PPD. Very interesting because Other than a regulatory agency, so CROs have the broadest view in terms of what the portfolios look like because they're working for many different sponsors at the same time.
Speaker: So, you know, if you wanted to understand what's happening in the world of depression, you know, CRO that's spending time in in in neuroscience and depression, you get to see different molecules at different stage of development, different mechanisms, different strategies, different management styles. So that was very educational in the sense of, you know, what the range the range of kind of scientific sophistication, managerial sophistication, leadership styles, et cetera, that people bring to the table and the kind of ask or the kind of issues that they need help with from from from a CRO. So, you know, for me, those are all learning opportunities. And and I would say that the the thing is that as ah as a physician there was mo motility or mobility between these companies.
Speaker: um And, you know, overall, I'd say, you know, they were not all of them were the best decisions I've ever made, but I don't regret a single one a single decision of those. It yielded a lot of a lot of you know positive learnings.
Speaker: For me, I am less bound to whether I'm working for a large pharma company or a small company. they they have pros and cons and and you learn to kind of, you know, live with with with the context of each one of them.
Speaker: What drove me in particular areas was, could I get my hands on an interesting molecule? What are we working on? And then as I've gotten older and grayer, which you can't see because this is not going to be on camera. yeah Yeah.
Speaker: You know, who I work with has become really, really important. Right. The chemistry, the trust, the relationships, those, those, those, we those have become increasingly important over time. Yeah.
Speaker: And I don't think you can get to a much more interesting asset than what comp Compass Pathways is doing now. i mean, obviously, it's interesting to like everyday people because of like colloquially, like how how like of the idea of like what the actual asset is like, wow, they're using psilocybin for like medicine for drugs. And it's not like gimmicky science. It's real to all at the same time. um And I would love to like kind of hear. I mean, so after these decades from pharma to biotech, a CRO, um I mean, psychedelics carried a real skepticism. And I think that's changing today. I mean, all these psychedelic companies have been doing better than ever. Look at their valuations. But especially when you started and when they started from the scientific community, from investors and people just hearing about the space, um there was a lot of skepticism and like early failures. really did not help going in that way. So, I mean...
Speaker: you kind of made a personal bet in some ways on a drug in a field that hadn't proven themselves at scale. and And now they sort they're starting to do so. But I love to hear, like, what did you see Comp360 and in Compass that convinced you it was worth that bet? You spent time at a small biotech before.
Speaker: You're at a yeah larger biopharma company now. um What made you want to take that bet? And what's that been like so for you? And could you please also maybe walk us through what Compass Pathways does as you're going through it?
Speaker: Yeah, so maybe let me let me start there. you know Compass Pathways is is a company that's headquartered in the UK. Right now, we are completing our studies of COM360, which is a proprietary formulation of synthetic psilocybin.
Speaker: We've completed two pivotal trials in treatment-resistant depression. um you know The company has announced results, so everything that I'm going to share with you is in the public domain. We've had two positive, very positive clinical trials.
Speaker: We're in the middle of a rolling submission with the FDA. um And, you know, because it is psilocybin, the profile of the of a compound is known. And from a safety perspective, we haven't seen anything that would surprise anybody who's looked at the literature on psilocybin, right? So it does what it's supposed to do, and it does it in a way that has been described before.
Speaker: What was particularly attractive is that You know, making the leap from anecdotal data and studies that were done in the 1950s or 60s. Now, everybody should keep in mind that as of 1970, for 50 years, we paralyzed research with psychedelics because of this fear that there are, you know, somehow gateway drugs or and things like that.
Speaker: So little by little data started to emerge and you know started actually in the UK and some other some other regions about the utility psychedelics in treating people you know with end stage cancer and existentialist you know crisis and depression and helping them to to to at least have some quality of life.
Speaker: Signals of you know of of efficacy and depression started to emerge. And I think Compass did an amazing job. And I'm going to call out Guy Goodwin, who's the chief medical officer of the company, as an absolute hero in this space.
Speaker: Right. The company designed design in in in moran best inclass clinical trials course like could for psychedelic. No corners were cut.
Speaker: It was very well thought out. And in fact, we take it as an article of pride that the fda's got FDA guidance on psychedelic very much mirrors what we did in in our clinical trials. So you asked me what attracted me, right? It's high quality science. and I'm going to put my my personal reputation and name on the line.
Speaker: I'm not going to do something that's that's fly by night and you know shifting, right? So it's really high quality clinical trials. And along with that comes a kind of a a a responsible leadership and management to the company that is, you know, they're in there. They know what they're in for, right? It's going to be challenging and it's a new class and There baggage associated with it and there are people who are skeptics and there are also people are evangelists. And so for us, the the thing about it is you know to actually walk the high road and let the data do the talking and make sure that we're really clear about you know benefit risk and who are the right patients and what's the right setting to use this drug because it's not something you just give and walk away. This is a very powerful drug and people need to be you know monitored and supervised while they take it, right?
Speaker: And so that's that's a lot of what what drew my drew my attention to it. And, you know, on ah on a kind of personal, it's it's challenging. It was difficult. It's not a simple thing. Right. And I'm attracted to difficult problems.
Speaker: Any neurologist, any any physician that goes to work in neuroscience, particularly in in in industry. we are we are suckers for difficult
Speaker: Yeah. I mean, how could you not be? Right. You're kind of self-selecting for it. um And we can get into the science. But I think, honestly, the question that better fits our conversation is honestly more about like the trial design.
Speaker: I mean, the science is interesting. It's different than most um likeychi psychiatric drugs where you take it every day and then wait for a few weeks to feel a difference. Like you're doing this. um And like there's like longer effect sizes and like really the biology is it's different. You can't just like take it and go home. You're with the therapist. and And that's part of the reason why it works.
Speaker: um But I would be curious. I mean, like phase 2B, I guess this is all public also. Phase 2B had like um a meaningful effect, but like durability was an issue. It seemed like phase 3 was more like the effect sizes. And now things have been looking really good in terms of the recent readouts.
Speaker: But When you're thinking about this, like you want to get the drug in the right situation, you want the right data, you want to preempt what the regulators really care about. um Like, what's your role been like and how have you been thinking about clinical trials, the design, the regulatory package in order to answer the right questions and get the right data across? Because, yes, like all data, you want it to be high quality, but you also want the right data, too, as you know. Yeah. So. so So we are sharing everything with the FDA. We're not cherry picking. They get to see everything. They get to see the raw data. They're going to analyze the data on their own and make sure that their analyses concurs with ours.
Speaker: um Our data suggests that on average, it you know, treatment with Comp360 provides a clinically meaningful benefit, but it doesn't work on everybody.
Speaker: right And I think we're going to be very clear about that. right The beauty of this class of compounds is that patients will know and their clinicians will know fairly quickly whether you've responded to the treatment or not.
Speaker: And that's borne out in the data. You you can see within 24 to 48 hours, patients will report to you, will tell you that they're feeling, and it's not about the psychedelic experience, they're reporting changes in your symptoms. right And that was sort of carried out. So as opposed to a classical antidepressant where be treating for six plus weeks to see, you know, a modest change that accrues, here you're absolutely right. It's a qualitatively different approach to to to to treatment, right?
Speaker: And so there are going to be discussions about who are the right patients and what happens if they don't respond or if they do respond. you try a second or third round, right? That's sort of the discussion we're having with the agency. And and we are, you know, we've put the data out there. You know, we, from the O6 study that we put out there suggests very strongly that two doses, three weeks apart is probably a good thing for patients to start with, right?
Speaker: But that's that's sort of what what we're what we're going to be dialoguing with the agency to make sure that they understand or they they see the benefit-risk proposition. right So again, from from from my from my job is to to kind of make the arguments as clearly and as transparently and as robustly as I can to any audience, whether it's the FDA, MHRA, patients, families, payers, right? that stuts that's That's our job is to is to be very clear and in making sure that we communicate what we think is the appropriate benefit risk here.
Speaker: Yeah. In some ways, it's again, like, let data tell the story, let high quality data tell the story as you spoke on earlier. Yeah. I mean, there's there's there's there's there's kind of a, there's kind of a it's it's I wouldn't say it's an inside joke, but Good medicines, really good medicines. You don't have to work hard at selling them, right?
Speaker: The value is pretty clear. And I think we have one of those. Yeah. Yeah. And I think that's like also integral to you, of course, putting your career on your line and not on the line, but like your, your reputation matters when you work at a company like this and it's, I'm, I'm glad it's been working out well. And if come through, see is approved, it would be the first classic psychedelic to reach patients in prescription medicine from what I know. And I think that's, would be a milestone for yes, compass, but also for a field that's had to share a step back, setbacks and criticism, like The em mean the FDA rejected Lycos for MDMA and PTSD, and now Comptis is testing Com360 for PTSD from what I understand.
Speaker: And I think that's interesting. and It would really open the question that like looking 10 years out, if Com360 is approved, What does success look like both for Compass and the industry and how we treat mental illness? Like when you're thinking about, I know most of your questions are what happens in the next year, but if we can step out, it can be 10 years from now. Like, what do you see changing if we can have these successes in this field?
Speaker: I mean, I'll put a crystal ball on. Look, you know, I think that there are there are a number of other serious mental health disorders that share probably an underlying pathophysiology with treatment resistant depression. And that's in my in my view, OCD, substance abuse.
Speaker: Right. um And PTSD. and And I don't know that we have time now, but but there is probably a common kind of dysfunctional network or system that crosses and it has to do with sort of, you know,
Speaker: highly negative prior beliefs that are self-referential and self-reinforcing. And at some point if your sense is you know, I am worthless, I don't deserve to be loved, I don't deserve to be happy, and you can see that in terms of, you know, PTSD in the sense of, you know, the they're also negative referential thoughts. So if I project down, I say, look, you know, this class of medications,
Speaker: has the ability to change those kind of prior beliefs and change the networks and the circuits underneath it, right? So success for me is actually a shift from these are unrelated disorders and they're, you know, phenomenologically just described and say to a sense where we actually try to understand what do they have in common and why would this class of drug actually work across a number of currently disparate disorders?
Speaker: I think A, that will do patients a huge favor because PTSD and and depression are first class neighbors, right? Most substance abuse disorders carry an element of depression or anxiety, et cetera, cetera. So they're not completely isolated.
Speaker: So I think first and foremost, we can bring benefit to patients. And then as a kind of almost side benefit, it helps to restructure the conversation in psychiatry around moving away from DSM-like classification, which is not helpful, to something that is much more biologically oriented. And we can talk about disorders that have similarities in terms of their underlying pathophysiology.
Speaker: And this has been a longstanding problem in psychiatry. there's there's There's a huge problem with the way it's actually
Speaker: The semiology of psychiatry is, is, is problematic for many reasons. Right. And the ability to get a compound approved that can work across this disorders, but actually show that it works because it does something similar in different, different.
Speaker: I think that would be for me, it's not 10 years out. It's sooner that, but I think that would be a remarkable, remarkable legacy for, for com 360 or other classical psychedelics. Yeah, because I think it's interesting that so many diseases within a disease, depression could look wildly different. But between diseases, depression could look very similar to alcohol abuse or substance abuse more broadly. And I think that once we get it, it's not even just a biology fact, but like once we get this asset, hopefully, and other um indications, we can actually see this kind of effect and hopefully draw those by constellation together.
Speaker: um But I'm excited. And I think it'd be great if we get to us talk about this more and like the science. But um This is a huge discussion that we had. So we really appreciate the time again, Dr. Gold for walking us through your career and also just what's going on with comp Compass 360, Compass Pathways today. I'm excited. I've been excited ever since I majored in neuroscience. um The science is far beyond me, but I think it's really interesting. So um I can't wait to see what happens. The nice thing for you is that, you know what, you're you're going into the field at a really exciting time, right?
Speaker: I mean, I want to trade places with you for a couple of days.
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