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Ep. 10 Dillan Dinardo on Communicating the Breakthroughs in Psychedelic Medicine
49 Plays8 months ago
Dillan Dinardo is a seasoned healthcare investor turned psychedelic medicine leader. Join us as he discusses how psychedelic medicine is the next frontier of mental health care, and how the field is driving scientific innovation to transformative change.
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Transcript
Introduction and Mission of Spark Time
00:00:00
Speaker
Hi everyone and welcome to Spark Time. I'm Dani Stoltzfus. And I'm Will Riddle. Of Mighty Spark Communications. Our mission is to use scientific innovation to drive transformative change. We believe that compelling storytelling is the most effective tool we have in our arsenal to motivate and inspire audiences to invest themselves in audacious goals. We are scientists by training, storytellers by experience, and entrepreneurs by nature. Let's get started. Quick update
FDA Committee's MDMA Decision
00:00:29
Speaker
before we get started today with our discussion around psychedelic medicine with Dylan DiNardo. Between the time of this discussion and the episode release, an FDA advisory committee voted to not recommend ah FDA approval for MDMA with psychotherapy after a phase three trial ran by Lycos Therapeutics, and we refer to this trial during the conversation. So committee members cited missing data as well as difficulty assessing the two trials on the basis of blindedness.
00:00:59
Speaker
Also, a number of allegations that negative data was not well reported by patients and people involved in the study has come to light. So, while this is disappointing news, the FDA will make a decision about issuing a new drug application in August. And should the FDA not approve the drug, I think this conversation with Dylan shows that the field isn't going anywhere. Psychedelic
Guest Introduction: Dylan DiNardo
00:01:20
Speaker
medicine drug development will continue and a number of advancements are going to develop in the near future. Today, we're sharing a conversation we had with Dylan Donato, a former healthcare investor turned psychedelic medicine CEO who's a graduate of the Y Combinator Program. I really liked the way Dylan described the advice he received during that time with respect to pitching, which is to be simple and direct. Good advice for a diverse audience.
00:01:48
Speaker
Yes, definitely. That is advice that never expires, Danny. Personally, I was very interested in the history lesson that Dylan provided. Much of our knowledge of the pharmacology around psychedelic drugs has been collected and reported in a very different way than our knowledge of most other therapeutics, and he dives into that. Yeah, that's really true. And to take it really high level for a second, I've been exposed to the trauma and heartbreak that mental health illness can cause over and over again, actually. So it's really refreshing to see a new approach to treating these illnesses. And I love how Dylan shared his own personal experience, which fueled his passion for the field.
00:02:28
Speaker
Definitely. Let's dive in. Dylan DiNardo is the CEO of Mindstate Design Labs, a next-gen psychedelic biotech company designing novel states of consciousness for mental health therapeutics. The company uses first-hand human experience, large language models, and biochemical data to map the biological basis of psychedelic experience and precision design alterations to the constructs of conscious awareness. Mindstate Design Labs was in the Y Combinator summer 2021 batch and raised a seed round led by Initialize Capital with participation from a number of other VCs and Angels including founders of OpenAI, Neuralink, AngelList, Coinbase, Instacart, and Twitch. Prior to Mindstate Design Labs, Dylan worked in a billion dollar venture fund, executing and managing more than 50 biopharma, medical device, and health tech investments ranging from pre-seed to publicly traded companies.
00:03:19
Speaker
In addition to his investment capacity, he held operating roles in the spin-out of over a dozen early stage companies. Awesome. so If you wouldn't mind, could you tell us about your journey from venture capital to CEO of a psychedelic medicine company? What made you make that big jump?
Dylan's Journey to Psychedelic Medicine
00:03:37
Speaker
Sure. i i it's ah It's a great story. um it was It was not really a career choice. It it wasn't really a choice, even. it it was It was more something I was compelled to do. um i I do love venture capital. I love being at the the edges of technology, especially on on the biotech side, where technology has so much potential to make such an immediate impact on people's lives, on on people's health.
00:04:04
Speaker
um And so that was it was a rewarding career. I definitely loved what I was doing. um But there was something that was, I suppose, closer to my heart, which which was the potential of psychedelics specifically. um And i I came to that technology from more of the personal side. So this was a number of years ago ah before psychedelics were claiming all these headlines about being the next generation of mental health care. um And I was an early adopter, so to speak. So I had my own psychedelic experiences and in legal you know controlled settings with medical supervision um and and kind of firsthand saw what an impact they made. But it was not specifically the the healthcare potential. It was more how psychedelics opened up this this concept of consciousness and had the potential to to give us the keys to understand consciousness much more concretely. um
00:05:07
Speaker
and And so I saw through a variety of experiences with different compounds that different psychedelics do very different things to consciousness. And it's a very abstract, difficult concept to to talk about. um it's I like to use the metaphor. it's It's kind of like trying to tell a fish that there is another type of water called land. and other types of water called air and space. and you know if in In this conversation with the hypothetical sentient fish, ah that the fish would probably just you know look at you like you were crazy and and have no idea like what's water. right so
Exploring Consciousness and Psychedelics
00:05:41
Speaker
so Water's just everything around it. It's it's our environment. It's our reality you know and in this fish example. and Consciousness is the same way for us. um and so Seeing that
00:05:51
Speaker
the self-reflexive awareness that just forms our entire user interface with reality, seeing that that can be changed in in fundamental ways that I couldn't imagine, um and seeing that it can be changed differently by different compounds that had different pharmacology, um just just led me to this this question of of what is consciousness and and what's the computational basis of consciousness and what's the biological basis of consciousness and how can we make fundamental progress on this to be able to ah to do a number of things and including the the impact to mental health care that that we can make. um And so it was that that that journey and and that quest that just really gripped me and and possessed me. um and and And so I just went out to the scientific literature looking at what do we know about how the divergent pharmacology of psychedelics leads to these different states of consciousness. And and there was ah there there wasn't a lot out there. um So I teamed up at that point with our scientific founder, who is Dr. Tom Ray, who ah has a fascinating background making seminal contributions to multiple fields of science. But he is he's most famous for creating the first instance of evolution by natural selection after life on Earth. So this was the world's first artificial life program. um
00:07:14
Speaker
So he's an evolutionary biologist. He is a computer scientist. He was ah a close friend and collaborator with Ann and Sasha Shulgin, who are known as the godparents of psychedelics and and created most psychedelic compounds that exist today. um and And so we teamed up based on this this common vision. And the actual transition from VC to CEO was was really um a very ah sudden transition after a a long period of of exploration. So it was really that trigger of of Y Combinator that that kind of compelled me to move forward. ah So that's I believe that's pretty much the
Pitching at Y Combinator
00:07:54
Speaker
background of the story.
00:07:55
Speaker
Such a great story. Yeah, I really appreciate the analogy that that you bring up this fish in water. And I also appreciate the the conviction that it takes to say, with this analogy in mind, we're we're going to we're going to study that, we're going to change it, and and we're going to make real strides, fundamental strides in science to to get there. So very cool story. And yeah, I think we should come back to the the Y Combinator, Danny. Yeah, first of all, I think I'm going to be this fish that's like, but there's only water. like How can there be land? like I understand the words, but I can't imagine the concepts. I find this topic so fascinating. but yeah so Let's go back to Y Combinator, like Will mentioned. Obviously, you know
00:08:40
Speaker
You had to sell this concept to somebody at some point to raise investment. and We've heard that a lot of the initial money that went into the mind state design came from a one-minute pitch that you did on a Y Combinator demo day. i mean Can you tell us what it was that you said in that one minute about such a complex scientific story that had investors so captivated? Yes, I can. To talk about the context a little bit, so why Combinator has this concept called demo day, which is often a thing that accelerators do where there's one day at the end of the program where all the companies are are pitching and a very large number of investors are are gathered to to hear the pitches and find their favorite companies. um and and so That 60 seconds that you get to give your initial pitch, everything really hinges on that 60 seconds. um and Of course, afterwards, there there are many follow-up calls and longer pitches and due diligence and and so forth, but that 60 seconds is crucial.
00:09:39
Speaker
um the but One of the great things that Y Combinator teaches is how to be, I think, more simple and more direct. So it's it's not all of these fancy communication techniques. It's more um get rid of all the baggage. um say it like you would say it to to to a child, um the best communicators are able to take very complicated concepts and condense them down into very, very simplistic things. And and really, um that that communication is is not a it's not a distillation, it's it's actually more clear than telling the whole complex story. um So our slide was was just a series of a few bullet points. And and we made the point that
00:10:23
Speaker
psychedelic medicine um was likely going to become the next generation of mental health care. And and we just made that with a simple point that the first psychedelic compound to enter phase three trials, which was MDMA, had a remission rate. So essentially a cure rate of about 67% in treatment resistant PTSD patients who on average had ah PTSD for 18 years before their three sessions with MDMA. So, just just that one simple stat coming backed up from a peer-reviewed journal, coming from a an FDA you know-controlled clinical trial, um and that stat which which just blew away the standard of care in in PTSD, certainly by orders of magnitude, um was enough to establish the potential here.
00:11:10
Speaker
um and And then from there, we went on to to establish how the next generation of psychedelics had had so much potential to be more reliable, to be safer, to expand our our understanding of consciousness and our ability to use these different states and different treatment applications. um And then just a bit on the the founders and the team, just having an all-star team in place, is is really a crucial factor for early-state investors. So we spent just a small amount of time on on the team, and that was the 60 seconds. Wow. I love that. I love the concept of direct and simplicity. like That is so powerful and soften ah overlooked so I think there's a lot to be to be taken from that lesson. and yeah Thank you for sharing.
00:11:59
Speaker
So you had mentioned the the recent phase three trial with with MDMA to treat PTSD um in combination with psychotherapy. And you know with that phase three trial, acceptance of psychedelics and and their analogs is as therapeutics is definitely growing. So between the time when you when you were first making this pitch, let's say back in in the Y Combinator days and now, How has your communication strategy evolved as more psychedelics are progressing through clinical stages? There are definitely more stats to quote. yeah you know but Week after week, month after month, there are better stats and and more evidence. and um you know i I had my own personal story of of encountering psychedelics in this type of of controlled environments. and and what they did for me. And I was diagnosed in the past with PTSD, with major depressive disorder, with ADHD. And and soon after that encounter with psychedelic therapy, I no longer qualified on any of those rating scales. So that personal story is is helpful. right and And so I saw that that firsthand. But it's also an anecdote. right I can't you know claim that psychedelics cure these mental health disorders. based on on personal experience, even though there are many, many others so um just like me. So what really matters is that that clinical data, and as the clinical data has grown and grown, the concerns of investors, the concerns of partners and team members have been not so much, know will this work? um and the The concerns definitely change more toward the ah the practical implications of what what does the infrastructure look like? What are the logistics? what What's the protocol that's required for these types of therapies? What are the um insurance implications? and and so
00:13:50
Speaker
Certainly, yeah as as we started this process, the clinical data was much earlier. And even though these stats were very impressive, it was these were earlier trials. Phase one, phase two, smaller number of patients, small efficacy signals, even even though the the rate of efficacy was very high. um and And so it's just become easier and easier as there are more stats to to refer to. But from the very beginning, we always just led with, here is the clinical data. um because that's what matters. and and Fortunately, as as we expected, the clinical data has has gotten better and better and has not ah deteriorated over time. and and so um That's fundamentally one one of the pillars that we base the pitch on.
00:14:33
Speaker
yeah i i really I mean, it's just so fortunate that so much good stuff is happening in this space, not for you, but for everyone who benefits from it. But I see how that really strengthens your your communication story, that you can always highlight clinical data and the fact that there's more and more of it. And it is so promising. I mean, it's a really exciting space to be in. and I think that in my mind, having you know worked in drug development, we always think about you know having a de-risk regulatory pathway because that's one of the easiest ways into the clinic. But obviously, the path that you're charting is very tough. right it's It's relatively new and there's a lot of history and potentially opposition to having psychedelics be um approved drugs. so
00:15:21
Speaker
How do you think about like endpoints in the clinic? Because obviously, they're going to be a bit different to how we traditionally think about endpoints in clinical trials. How do you anticipate communicating this sort of information with the FDA?
FDA's Role in Psychedelic Trials
00:15:36
Speaker
Well, the FDA has been extraordinarily supportive. And we we are the beneficiaries of a lot of people who've done a lot of work over the past few decades. So there are nonprofit organizations, for example, who've been pushing forward drugs like MDMA and psilocybin. And and that has been a decades-long process of of working with the FDA and working through the data and and making sure that there was a a very deep understanding of the benefits and the risks and the trade-offs um the the proper protocols for mitigating any risks that there might be. um And so we are definitely on the tail end of that process where the nonprofits have pushed the science forward for decades um and now things are at the stage where commercialization is is happening and commercialization is viable.
00:16:23
Speaker
um And so the FDA is is no stranger to the science here. they They are very deep into the process. There have been many, many psychedelic trials at this point. um And so we've we've found them to be incredibly supportive. um We had a a great pre-IND, yeah, it's been absolutely wonderful. There was a great pre-IND call at the beginning of this whole process where we were able to just have a back and forth with the FDA. um At this point, they have also released guidance documents on how to run psychedelic trials. So um this this isn't quite as much of of an edgy area of science as you might expect from the history of the compounds. So Dylan, I'm kind of curious about, because we're talking about endpoints, can you tell us a bit about how
00:17:11
Speaker
these these effects are are measured in the clinic. Now, it's my understanding that for a number of psychedelic, I think maybe all psychedelic drugs, we're not measuring a biochemical change in the brain, but but rather how people are the behavior of people. Is that correct? Yes, the primary
Measuring Psychedelic Effects
00:17:29
Speaker
outcome measures here are usually subjective reading scales, yeah usually clinician administered. and And so there's a different scale for each of these diagnoses. um And the the interesting thing about psychedelics is that the mechanism seems to have transdiagnostic applicability. um So there there are a wide variety of disorders that are associated with a a narrowed mental and behavioral repertoire. So depression, anxiety, PTSD, OCD, um phobias, substance use disorder, many of these types of disorders seem, in early clinical data at least, to ah greatly benefit from psychedelic therapy with the the right compound in the right context. um But it it is all mediated by the subjective experience of the patient. um so So first, the subjective experience of the altered state of consciousness, which is an acute and transient effect.
00:18:28
Speaker
um So, it's it's temporary. um And so, we have a variety of rating scales that attempt to measure these types of effects. So, one example is the 11D ASC. It's an altered states of consciousness scale. Another scale is the MEQ-30, the mystical experience questionnaire. um So, these are are very woo-woo terms like mystical experience, but the these are quant Quantitative, but that's effective rating scales. And then when it when it comes to treatment outcomes, it is interesting how the the treatment outcomes highly correlate with those subjective experiences. um But the outcomes themselves are your typical ah scales that that you would use for any other type of, say, depression treatment. So that there's a ah there's the Mater scale for PTSD, there's the clinician administered PTSD scale. um and and And so these endpoints are are subjective, but it's it's very interesting to be in the realm of psychological mechanisms where it's not necessarily that a drug hits a certain receptor.
00:19:34
Speaker
right So if if you give someone MDMA, which is commonly known as as ecstasy, and you send them to a rave, it probably does not heal their PTSD. right um what What helps is if you administer the drug, and so that the patient is then entering that state of consciousness, is is having these changes to mood and cognition, where they feel this overwhelming sense of empathy, both for for other people as as well as for self. um And they get this fear extinction where all is well with the world and and they're able to safely contemplate mental pain and in this environment where you're removing distractions, right? It's not a loud environment with lights and pumping bass music. It's it's rather a chair they're they're kind of reclined in with a blanket, with eye shades, with
00:20:22
Speaker
ah headphones with specially designed music to help the experience be introspective. um And it's the it's putting this kind of treatment in a setting where the intention and the expectation is a therapeutic one, is an introspective one. um and And so when you set the direction of of the patient's attention and the patient's thoughts, ah in that way, you are combining this acute state of consciousness, right this this altered pattern of brain connectivity that is expressed in the phenomenology of an altered state. You're you're driving that into a specific clinical protocol, and and it's that dynamic um occasioning of of the higher order brain structures interacting with the environment that really um causes the the treatment response. And so when we talk about biomarkers and and outcomes, the thing that we're most interested in is how the the phenomenology drives the outcomes.
00:21:18
Speaker
um We believe that that it is the altered state itself. It's that acute transient state that drives the outcomes. We may be completely wrong. the The acute state may just be the biomarker that that tells us whether or not the the outcome is going to happen. But either way, the the two are very linked, the the altered state and the outcome. um And so that's that's basically what we base all of our our science around is in intentionally designing these states of consciousness and and specifically the types of states of consciousness that's that are effective for a given given disease indication. So as an example, auditory hallucinations, for example, hearing voices probably not very helpful in therapy. ah But if you take something like the this mystical experience, which which deals with things like a profound sense of sacredness or a loss of the sense of self or a sense of awe, or a transcendence of time and space, these are sub-factors of subjective experience that highly, highly correlate with treatment outcomes. um And so designing states that that really do correlate with treatment outcomes can have profound effects on on patient outcomes rather than it being a toss-up of, you know, a psychedelic drug, you're going to experience all the contents of your subconscious. Good luck. yeah um it's It's we are designing the state of consciousness, here's what you will experience. And um and there will be a a much higher rate of predictability, both with the state of consciousness and and theoretically here with the treatment outcome as well.
00:22:51
Speaker
Fascinating. And if I can piggyback on that question and your response, is mind state utilizing different drugs to induce different states of consciousness? I imagine it it's not all MDMA, is that right? ah Yes, that's correct. So psychedelics is a pretty broad term that encompasses a number of different drugs with different mechanisms of action. um The classical psychedelics are things like LSD and psilocybin, which is the primary psychoactive ingredient in magic mushrooms, um along with mescaline and and DMT. So these are what are commonly referred to as the serotonergic psychedelics.
00:23:29
Speaker
So, the the main ah target here, the the main pharmacological target is the serotonin 2A subtype. um and And so, what we are looking at is a a wide variety of drugs. So, I mentioned Sasha and Ann Schulgen earlier, the we go parents of psychedelics. um Sasha had a DEA license back in the, this would have been around the 80s, and this was completely legal at the time. I don't know how, but he would just create new psychedelic drugs. and eat the drugs and he would titrate up and and report on his experiences. Terrifying. and so Yeah, like the courage to do that. yeah Gosh, that's pretty incredible. um But because of of what he did, hundreds of drugs have have been in distribution basically.
00:24:17
Speaker
um So, they they published all of their synthesis and their experiences in a couple books in the 1990s. And as a result, there's this subculture within the psychedelic subculture of people who like to experiment with the more exotic compounds and then report in detail on their experiences. So, what we have is is not just this wide variety of drugs, but through through Tom Ray's work, we have all of this pharmacology on the drugs. So, we we understand um with with wide-scale assays across the brain. How are these different drugs interacting with the brain in different ways? So we're not just looking at how different drugs cause different states of consciousness. We're drilling down to to deeper levels to understand at the pharmacological level which particular targets in the brain interact with with other areas of pharmacology to create which patterns of brain activity and which altered states of consciousness. So it's truly designing a state of consciousness, the equalia of
00:25:13
Speaker
a conscious experience from the ground up. you know Following on from everything you just described, Dylan, what's happening with mind state in the next year or so? What
Mindstate's Human Trials
00:25:22
Speaker
are you really excited about? Well, we've wrapped up animal studies with our lead compounds. So we are expecting to start human trials very soon here. So we're very excited about that. And it's a bit too well to think about ah giving psychedelics to humans in in that FDA approved context. So, ah yes, getting into that that clinical trial is extremely exciting. What we're we're doing is a combination approach where we we have two different drugs. So, our first drug, we call it our primer, and it's really the backbone here. um yeah People refer to this drug as psychedelic tofu. um So, it has this reputation, even though it has has never really been studied. in a
00:26:04
Speaker
clinical or really scientific context before it has this reputation for taking on the flavor of whatever else is co-administered. And unlike most psychedelics, it it has specificity for the serotonergic system. So it allows us to to kind of do this A-B testing. and It allows us to take this drug and combine it with various other drugs that are already approved generics, um but that bring in some other pharmacology that we're identifying as as relevant to the inducement of a specific state of consciousness. So, this trial is is itself a a platform. um So, we're we're running the trial with this drug to prove out the safety of this particular psychedelic drug, but it's not just a single drug. It's a a long series of drug combinations that that we intend to use to get different states of consciousness for each one.
00:26:53
Speaker
um So, getting to that proof point where we show the different combinations causing the different states of consciousness as we have predicted, um that really opens up an entirely new world, not not just of psychedelics, but redefining the psychedelic space as um as the ability to precision design consciousness itself with with pharmacology as as only really the tool to doing that. ah That's what I'm most excited about over the next year or so. So as a final question, we we love to ask this question and that is with all your experience as a founder and working with founding teams combined with your experience in VC, what would you say is the most valuable piece of advice you could give someone who is in the position of starting their first company in biotech?
Advice for Biotech Founders
00:27:41
Speaker
Hmm, I might say don't listen to advice because you are it's you're your own person, right? and And you have your own circumstances. And i'd'd I'd say you know rather than listen to advice, maybe maybe listen to many, many pieces of advice and take take what you can and and chart the path that ah that's right for for your particular situation. But um I can certainly share what worked for me specifically and in my situation. yeah and And that started with um I guess it starts with ah with interest, with with passion, with what grips you. um And a great place to figure out where your passion might be is to to look at your scars, to look at what is most painful for you. Because the the passion for um solving that same problem for others often often starts with the self. And ah sometimes it's not like that at all. Some people are incredibly successful just um developing better ah HR software, right? But what worked for me was what was being obsessed with this one particular problem and the potential that that could come from investigating this. that particular mystery of of consciousness and how consciousness works. um And everything kind of flowed from that. So if if you find an idea that that it is just powerful in its own right, that that idea will call its own resources, it will call other people to it. And and so all you have to do at that point is is find the others, find the other people who are also obsessed with that problem and who are whose whose whose interest is just completely gripped by that thing.
00:29:22
Speaker
um And so that's that's what we did. And and the result there is you get um you get great people. The best people in the world want to work on on the most difficult, most impactful problems. um And as you get the the great people around you, then that that just sort of, in my experience, snowballs and and everything kind of flows from that. um so So yeah, my my advice there is is just to ah to to to set your goal as high as you possibly can. What what is the most meaningful thing that you can accomplish? And and the best way to find that is what what is the most painful thing that you know? And start there and and everything else flows. Incredible. Such good advice. Yeah. Dylan, I want to say thank you so much for joining us today. It's been such a delightful conversation. So thanks again for coming. Yeah, thanks, Dylan. Thank you so much for having me. It was great to talk with you.
00:30:12
Speaker
What a great conversation we had with Dylan. We had the goal of giving our listeners an overview of the psychedelic medicine field. And now I wish we'd had more time to talk with him about what he's excited for over the next five years for the industry. We just might have to bring him back. Oh, absolutely. It's always exciting to catch up with the psychedelic medicine field. We know that one of the broader critiques of psychedelic drug development is that there's no clear explanation of the link between a drug's chemistry and the associated biological effects. What I liked about Dylan's response to that is that he leans hard into the fact that the clinical data looks beyond promising. I mean, a 67% remission rate for PTSD in the recent phase three MDMA clinical trial, for example. So the effect is real.
00:31:01
Speaker
This is always a difficult part of drug development. And we can compare that, of course, to Alzheimer's drug development, where a druggable hypothesis like that of targeting amyloid beta has been difficult to prove as well as to provide treatments around. So really great discussion here. Yeah, I agree. And changing topics, I really enjoyed the advice that Dylan had with founders, you know, to look at your own scars and how you solve them and then apply that knowledge to solving the pain for others. This really strikes a chord with me and was one of the motivating factors for wanting to found Marty Spark Communications.
00:31:39
Speaker
I lived through so much pain in terms of effective communication, and I wanted to share my knowledge with others on how to be really effective at telling your narrative to the right audience at the right time. Dylan opened up this ongoing conversation in the field of, does the acute state of consciousness drive the remission outcome? Or is it the phenomenology of the experience that enables remission? As in, are the great effects in mental health coming from certain pathways in the brain being activated? or from the experience itself? And this is clearly an important question. And side note, he believes it's it's the latter of those two. But I appreciated how Dylan kept bringing it back to the solid data of the field is generating, and thereby focusing on improved outcomes for patients. Such a pro communicator.
00:32:28
Speaker
Yeah, that's very true. And I look forward to hearing, you know, continuous updates on the field and from Dylan as well. I hope our listeners enjoyed hearing Dylan's story and advice in communicating breakthroughs in innovation. We love talking about this and we'd welcome anyone who wants to continue the conversation with us. Join us next time as we continue to power scientific innovation with storytelling to drive transformative change and solve our most demanding challenges.