Backing Breakthroughs in Psychedelics

[00:00:00] Speaker A: And back sort of in 2017 or so. I also took a look at the venture fund landscape, and I saw that there weren't any venture funds that were specifically targeting and supporting the mental health space. There were some generous ones making an investment here and there, but it wasn't a focus. And so this is something that I became very interested and passionate about and wanted to, to kind of help, support and pioneer. [00:00:43] Speaker B: Well, Dina, thank you so much for taking the time to have this conversation. I really appreciate it. [00:00:47] Speaker A: Yeah, thank you for having me. Excited to discuss more on mental health and the new treatments. [00:00:56] Speaker B: Totally. So for the audience, Dina is the founder and CEO of an exciting company called Freedom Biosciences. But I'll give her an opportunity to kind of expand on that. If you don't mind just giving us a maybe thumbnail sketch of your career and what kind of led to this point. [00:01:13] Speaker A: Sure, absolutely. Yeah. So in terms of my career, started kind of more corporate, started investment banking, work for JP Morgan, then moved over to McKinsey, and it seems like that's something that we share in our background. Got my MBA and then moved to Silicon Valley about 10 years ago and have been primarily involved in building or investing in startups. So I consider myself a serial entrepreneur. Freedom Buy is actually my third venture. And before starting freedom buy, with Dr. John Crystal, who you've also interviewed, I co founded a venture fund here in San Francisco that's called Simed Ventures, which is an early stage venture fund focused on frontier mental health technologies, which basically means any technologies that could be FDA approved or cleared for the treatment of mental health and neurodegenerative diseases in the coming one to two decades. Right. I think we'll get into sort of what are the available treatments and right now, as well as what's in the pipeline to be approved hopefully in the coming years. And so, you know, I developed an interest in mental health about seven or eight years ago because I saw what a huge gap there was in these treatments. I think a statistic that really hit hard was that there's 300 million people that are living with major depressive disorder, meaning this is kind of pretty severe depression that is affecting people's lives across the board, you know, professional, personal. And while there's 50 and, you know, almost 60 antidepressants on the market today, 100 million people or a third of that population are left with no adequate treatments. Right. And it feels like you're living in, in the Bay Area and, you know, we're working on such incredible technologies and sending people into space, but we don't have treatments that are helping so many people that are struggling on a daily basis. In fact, sort of in 2017 or so, I also took a look at the, the venture fund landscape and I saw that there weren't any venture funds that were specifically targeting and supporting the mental health space. There were some generous ones making an investment here and there, but it wasn't a focus. And so this is something that I became very interested and passionate about and wanted to kind of help, support and pioneer. And so this coincided with some additional clinical data that was coming out across different psychedelics and in particular MDMA for PTSD and some early data on psilocybin for depression. And that data was just so compelling that led to this, you know, renaissance, as some call it, of psychedelics for mental health in the years to follow, which, you know, helped build this pretty large industry, biotech industry, services, healthcare industry around using ketamine and in the future, other psychedelics that will be approved for treatment of mental health disorders. So my two partners and I established Silent Ventures and we were one of the first ones to support psychedelic therapeutics. We also invest in neurotechnology and other frontier mental health technologies. Through that, I got to know the space pretty well and was very, very lucky to meet Dr. John Crystal in 2020, shortly after he published a paper on the combination of ketamine and rapamycin, which is a drug that many people who are interested in longevity might recognize. But this combination proved to be pretty incredible. That clinical study out of Yale showed that the efficacy of ketamine can be extended three to four fold. So what does that mean practically for patients right now? If you're treatment resistant, depressed patient, and basically have failed multiple different antidepressants, ketamine is one of your only options. Ketamine is incredible because it's the fastest acting antidepressant, works within a few hours and within 24 hours for most. It's also highly efficacious for those with treatment resistant depressed depression as well as suicidality. However, it's a cumbersome treatment, meaning patients need to come in about twice a week initially to remain responsive and in remission from their depression. And so what John Crystal's novel version of ketamine has shown is that that window can get extended to two to three weeks. So as a patient twice a week, you might only be coming every two to three weeks. And you know, when I saw that, I really thought it was completely revolutionary because this was one of the biggest impediments to the Adoption of ketamine and other more kind of interventional psychiatry treatments. And so John and I teamed up, we launched Freedom Bio, licensed to technology from Yale and have been building this company. We've progressed this program to be ready to launch into a phase two, a trial which, you know, just. [00:07:10] Speaker B: Congratulations. [00:07:12] Speaker A: Which is, you know, quite, quite far along in the clinical development pipeline with the FDA and have built a number of other drugs that are based in rapidly acting antidepressants such as ketamine or 5ht based triptamine or psychedelics in pathogens in combination with other drugs to really address the most, the biggest shortcomings of those antidepressants. Just to really make sure that we can increase access to drugs that are, have already been shown to be efficacious. [00:07:52] Speaker B: Yeah. And I'd love to hear your perspective having, you know, seen the landscape via your work at simed. Naturally, having made the investment in a tie, I think in the research that we were doing, some would say maybe you're thinking about this next generation of psychedelic or psychedelic adjacent therapies. How do you, how do you think about the landscape of maybe let's call them the traditional psychedelics versus, um, what you're intending to do here? [00:08:22] Speaker A: Yeah, um, I mean, I think I would start with kind of going back to the problem and how big it is in terms of the number of people. So a hundred million people don't have a treatment that works for them and the remaining 200 million people with MDD may also have not the most adequate treatment or at least be experiencing pretty significant side effects. Right. This is kind of a big impediment to a lot of the oral antidepressants. So it's a huge number of people that need help and the unmet need of these people is also very high. Um, so when we think about the different treatments that are being developed right now and that are going to come out in the future, my opinion is that there's space for dozens and dozens of new treatments. Right. So what that means is, you know, there's, there's sort of, let's say, let's take psilocybin, right. That, you know, a number of groups including Compass and Mesona are developing for different medications. You know, hopefully, you know, the data continues to be strong and they can get approval in the next few years. And then there's also these sort of net next gen, so versions of psilocybin, whether they're combos or derivatives of psilocybin, that are addressing some of the issues. Right. I think that there is going to be space for multiple of these treatments. The reason for that is first of all because the biology of a human, of every human is different. Right. And this is kind of evidenced by the fact that there are 50, 60 antidepressants is there's so many different SSRIs on the market. But patients very often need to go and do trial and error with these different drugs because it's very hard to tell which one of these or which cocktail of these will out why they work. Right. So I think there's an opportunity for kind of the first gen psychedelics as well as the next gens to be on the market. I think that will probably be the case for the next decade, decade and a half as we improve on the pharmacology and more of the next gens will be developed. I think the future is more with the next gens just because, you know, these treatments, the, the, the, the first gen psychedelic treatments are quite cumbersome, right? It's, it's a six to eight hour treatment. You have to be in the clinic. These are very specifically equipped rooms. They have to have sound insulation. Um, they're most likely will need to be two therapists or two people are with the patient at all times. And in addition to the treatment sessions, right, the six eight hour sessions, there also need to be these integration or preparatory sessions. So all in all it's a very cumbersome treatment which while effective, may only be limited to some number of people because it's expensive and we just don't have either the infrastructure or actually probably the biggest bottleneck will be the number of therapists that will be trained enough and the training is, is, is going to be pretty involved. These most likely need to be licensed therapists that then have additional training to do this. And so I think kind of bringing this back to what we do at Freedom is we, we, we really believe, and we are seeing this in the clinical data that these first gens are very efficacious. And there's also a way, I think that we can start improving on some of the shortcomings by, you know, reducing the trip, making the trip less intense or entirely eliminating the trip that would ultimately help make it more accessible to a larger number of patients. [00:13:12] Speaker B: Yeah, so talk to me about that. Like how, how do you design that out of an experience? [00:13:19] Speaker A: How do you design the trip out of the experience? [00:13:21] Speaker B: Yeah, like, or like the, the length of the trip. Like, like these dimensions. Like, like what actually, like what levers do you actually have there yeah, this. [00:13:29] Speaker A: Is a better question for like a scientist. [00:13:32] Speaker B: Yeah. [00:13:32] Speaker A: I think I can tell you in just very high level terms. I mean there's, there's three primary approaches. The first one, which I think is pretty widespread already is microdosing. Right. So I think this, this has been getting a lot of media attention and basically what that means is people, not patients. Right. But just people are taking smaller micro doses of the, of, of what, what would be considered a full dose of let's say psilocybin. Right. And while it can vary from person to person or even from time to time for the same person, these tend to be self perceptive doses. But then they still have anecdotally have shown to have some sort of effect. Right. I think things that I've read about is, you know, people are having some like heart opening or they're just feeling better about, with their anxiety or with their depression, etc. They've been a number of clinical trials that have not been conclusive on the actual therapeutic effect of microdosing. So I don't think there's any kind of definitive answer there. Then there is a number of group, there are a number of groups that are pursuing either full or partial agonism of the 5ht2a receptor in, in the psilocybin which it, which is believed to be responsible for the hallucinogenic or the psychedelic effect. Right. And there is a lot of discussion in the medical community and the scientific community about whether the psychedelic experience is required for the antidepressant experience. Is, are, are we blocking the antidepressant effects by blocking the, the hallucinogenic effect? There's no definitive answer. There's, as I said, there's a number of groups that are doing this research and we should be seeing this clinical research coming out, you know, over the next few years. There's preclinical research primarily in rodents that shows that there are some agonists that, that block the hallucinogenic effect as shown by head twitch. So head twitch is something. That's right. See for hallucinogenic effect in humans without, without significantly reducing the antidepressant effect. And the third approach is the approach that we have which is combining not creating a new molecule. Right. Or, or blocking the receptor. We have a different novel approach to this which I can't speak to in detail here, but we, we generated very compelling data preclinically to show that there's a significant reduction in hallucinogenic effect without dampening the antidepressant effect that Works through different mechanism, so not blocking the 2. A. [00:17:23] Speaker B: Fascinating. So take me into some of the programs that you're running and your kind of approach here at Freedom. [00:17:32] Speaker A: Sure. So our, our lead program is a combination which I mentioned earlier is that's coming out of Yale, out of John's lab. This is a combination of ketamine and an MTOR1 inhibitor. And this is the combination that in a phase two like study at Yale showed a significant extension of the therapeutic effect. Right. Basically, humans, human patients who had NDD or treatment resistant depression took, may, took ketamine alone and the same patient also took ketamine and combined with rapamycin. They were randomized into different groups, but the same patient had both treatments. And, and what it showed is that while the effect, the therapeutic effect of ketamine was significantly shorter, about two to seven days. Which is, which is, which tracks with, you know, hundreds of other trials that have been done with ketamine and esketamine. The combination was significantly more durable. So patients even, you know, a good portion of patients even after two weeks were still responders and in remission. What that means practically is this next generation version of ketamine can be taken much less frequently. You're a patient, right. If you're a patient who's living with treatment resistant depression, and many of these patients live with this for years, if not decades. Imagine needing to go to the clinic twice a week. Imagine needing to get a ride there. Imagine taking time off from work or needing to line up childcare. Right. However, you know, most, for most patients, it's one of the only treatments that's available. So the way we see this program is to become the least cumbersome treatment for this patient population because the other options are ketamine, obviously tms, which is transcranial magnetic stimulation, which is a medical device, stimulates the brain. That's about a six week regimen. And patients need to go in every day, five days a week for about six weeks. Right. So we're talking a whole different bodies of commitment and time requirement. The other one after that is ect, which is electroconvulsive therapy. Right. Which has a bad reputation but is, is effective. And that means that the patients need to go inpatient care, they're being put under general anesthesia and basically, oh, you know, there, there could be pretty severe side effects, including cognitive memory loss. So if we're looking at this patient population, it's a very high need and what's available to this patient population is very limited. So if we can get Them a treatment that's efficacious, fast acting and that they would only need to go in every few weeks, that that's a total game changer for this patient population. [00:21:14] Speaker B: Yeah, absolutely. To ask maybe the like, like a naive question here. Give given J and J has esketamine already kind of like through their, through their distribution. What do you like? Why? Why I guess a startup and not through the kind of like established kind of pathways of like an iteration on like their current generation of product. How do you think about like oh, the opportunity as a startup to do this versus like maybe JJ doing it on the back of their own, like their own existing approval? [00:21:55] Speaker A: Yeah, I mean I think that's a question that JJ would be best to answer. [00:22:00] Speaker B: Sure, yeah. [00:22:02] Speaker A: But I think just looking at and trying to understand how big pharmas work, right. It, it makes total sense that you know, something like this would be undertaken by a young company. You know, for the most part big pharmas, they have some R and D, but they tend to focus on the later stage, much more de risked assets and they would prefer that biotech companies, younger biotech companies would do the earlier work, would you know, take on the majority of the risk and then they would come in with some clinical data and you know, would get hopefully a large premium for the work that they've done. Right. And I think where we're, we're seeing kind of quite a few acquisitions at the phase two and the phase three and the phase three stages in cns, we have a pretty strong connection to this Bravado program. So first is through our Chief Medical Officer, Dr. David Huff, who was at Janssen or Johnson and Johnson for 17 years. For several of those years he led Spravato. He was the compound team lead. And that's basically, you know, you would call that person the CEO of the Spravato program, where hundreds of people report to him for the development of the entire program across different geographies for two indications. So David led it from phase two, he got it approved for two indications and helped commercialize it. So and this is now a person who's leading Freedom zero one's development, obviously John Kristol and Rob Berman's also. John Crystal is my co founder. Rob Berman is the head of our scientific advisory board. Their discovery that ketamine was an antidepressant in, in 2000 was what led to the development of and was the founding of the foundational IP for that program. So from a team perspective, we are definitely very close to that. The team understands Spravato very well and understands how Freedom01 has a significant improvement on what Spravato provides. [00:24:47] Speaker B: Absolutely. And in conversations with Hussein Imanji, who is also involved on the Spravato program, just an incredible story of how they kind of fought the uphill battle to kind of get something like this over the finish line. And tell me about the kind of other indications you're going after. I understand you also have something interesting with ptsd. [00:25:12] Speaker A: Nothing that we can speak about openly right now. I mean, I think ptsd, again, another indication with a huge unmet need because there isn't an approved treatment for PTSD right now. As you probably know, mdma, Lycos, MDMA was not approved and they're hopefully going in for another round of, you know, trials to, to re. Return back and seek NDA approval. Um, but that's something that we're actively thinking about and you know, looking at some of the clinical data that's been generated with various psychedelics. Right. And the reason why I say this can be, yep, it's larger than psychedelics, you know, also NMDA receptor modulators, the 5ht2 based psychedelics, and as well as empathogens. So that's something that we're actively thinking about, but not something that I'm able to share just yet. [00:26:19] Speaker B: Yeah, absolutely. So as you, as you think about this Phase 2A that's coming up, what is what's most on your mind in terms of designing the studies and making sure that the kind of program is able to, to be successful? [00:26:37] Speaker A: Yeah, I think it's. In many ways this, the task that we have is much, much more simple than I think it is for other similar, you know, neuropsychiatry drugs at our stage. But there's obviously kind of the usual concerns. You know, a clinical trial is a very complex process. There's a lot of things that could potentially go wrong. And the partners that you choose in that process, like your CRO or the clinical sites that are running or the various vendors really matter. Right. So, you know, something that keeps me up at night is just making sure that everybody is doing their job and there's good flow of information. And, you know, I think we were ensuring that that's the case by having a really great team and also having chosen really good partners. I think neuropsychiatry in general is, is a tough space. That's why I think it also is so impactful. There is a new drug that's, you know, showing efficacy and coming to market but, you know, it's, it's the placebo effect can be potentially high depending on how you design the trial. And this is why we've been so thoughtful about how that's done because we've seen a number of trials that, you know, have, have shown certain results. And, you know, it's confounding whether, you know, whether it's, it's the design or the drug isn't as efficacious. Right. And that would just be a real shame. I mean, I think the other lesson that we're learning from Lycos's interaction with the FDA is also the blinding effect. Right. [00:28:56] Speaker B: Of course. [00:28:57] Speaker A: Hard to blind a psychedelic, you know, and however, there are ways to do it, and I think Spravato has successfully done that. Right. Ketamine is, also has very strong dissociative and even potentially hallucinogenic effects, but there's ways to blind the effects by introducing some other variables into it. And so we're, we've also been very mindful of things like that in designing our trial. So hopefully that's helpful. [00:29:35] Speaker B: Well, Dina, I'd love to maybe switch gears a little bit. How do you think about the, like, the kind of evolving patient experience then if it's all, if this all goes really well. Right. Like, we're in this, like, renaissance. There's a, a handful of companies that are pursuing really interesting things like how are you envisioning the kind of patient experience to kind of evolve over the next 10 years? [00:29:58] Speaker A: Yeah, I think the, a, a huge paradigm shift that's already started. And I think in a big way, Spravato has been pioneering that is, is the shift to what is called interventional psychiatry. Right. So, you know, the way psychiatry has worked is, is, you know, you go, you sit across in a chair or a couch across from your psychiatrist. Maybe there's some talk therapy in conjunction with medication prescriptions. But it, it's been primarily oral antidepressants. Right. And I think because there's a limited therapeutic effect for this treatment resistant population, there's been a shift to starting to have patients go into clinics because that's where the treatments are available. And we covered those. This is tms, this is ectamine in particular. And this has been kind of a slow shift because it's not what this space is used to and it's cumbersome. It's more expensive than oral antidepressants. We're Right. And, but what we're seeing is now the shift is really expediting because patients are Needing the help. And there's more acceptance towards these interventional psychiatry methods. You know, ketamine's definitely been gaining a lot more kind of popularity where patients themselves are learning about it and then bringing it up with their psychiatrists. And many psychiatrists are not set up to. To provide ketamine. Right. Because you need a setup. You either need kind of an IV setup to be able to administer IV Ketamine, or even with Svato, which is a neutrin hazel spray, you need a room where the patient can kind of have the experience and then stay for another two hours and be. Be monitored. Right. By. By a professional. And most psychiatrists is just, you know, it's a couch in a chair in. In a room. And so what we're seeing is. Is growth in the number of clinics that are providing either, you know, one or multiple of these. Of these treatments. And I think that's to. Going. Going to continue accelerating, and we're gonna hopefully have, you know, as I said, dozens new treatments in the interventional psychiatry space, including psychedelics, including intactogens and other, like, medical devices that are gonna be approved. So we can add to that because, again, every patient's biology is very different. So something like, if TMS is extremely efficacious for one patient, it's not. It's not gonna work. It's gonna have, you know, some side effects for another patient. And so our job as, you know, people who are trying to create more treatments is to. Is to provide more options to patients. [00:33:38] Speaker B: Yeah, I think I. I wonder, especially with. To your point, this. This kind of advent of interventional psychiatry is like, how does the kind of treatment algorithm or pathway, like, start to evolve for individuals? Like, do we think that it's going to still be trial and error a few times with oral SSRIs and then kind of working through to this or, like, what's the vision here? [00:34:09] Speaker A: I mean, hopefully not. I think, hopeful we'll be moving away from trial and error. There. There's. There's a number of groups that are working on various, you know, diagnostics and biomarkers that are. [00:34:25] Speaker B: Alto had a positive interim readout recently, right? [00:34:29] Speaker A: Alto. [00:34:30] Speaker B: Yeah. [00:34:31] Speaker A: Yeah. So Alto is definitely one of these groups that are working on, you know, how do we. How do we, you know, try to use some biomarkers to. To better predict the most efficacious treatment for this patient? And I think there will be some really great developments on this end, and we can save a lot of heartache for the patient, and we can also save kind of Resources for, for the system overall. There isn't anything that I think is very concrete right now to sort of share, but definitely interesting things in development. [00:35:16] Speaker B: Yeah, I think there's a, there are a few really fascinating trends in psychiatry, not only among psychedelics, but precision psychiatry and then also like tms, for example, changing the landscape. That hasn't been changed for a very long time. Yeah, well, there, in, in kind of like a, in wrapping up here. I'm curious, like, what question do you not get asked enough that you would like to get asked more? [00:35:44] Speaker A: Truthfully? I mean, I do get asked this question, I really do, but probably would like for different set of people to ask that question. You know, and it's, the question is like, how can we accelerate? How can we help? How can we promote getting these treatments to market? Right. And I would like for that to be asked from the regulators. And I understand obviously that there's a lot that's on their shoulders, Right. To, to make sure that the drugs are safe, first and foremost, that we're not doing more harm. However, I think, you know, kind of going back to like, why wouldn't Janssen do the work that a small biotank does? Because they have so many more resources. And this is, I think, where, you know, smaller biotechs need the help of the regulators of the government to make their job. That's already very, very challenging. Just a little less challenging. Right. And I wish there was more, there was more kind of support on that end because it, it really like what biotechs do, especially in a environment that's as challenging as it's been in the last three plus years, is, is almost impossible. Right. And then when you're, it seems like you know, really going against the current and then, you know, the FDA doesn't meet his depths and takes months longer to just respond to correspondence. Right. And we're talking a few, few questions that could really help, you know, move the direction one way or another. This is not just the FDA we're dealing the same with, with other similar bodies that are outside of the US Is can really make or break a program and potentially like totally tank a treatment that could be efficacious. And so I'm not sure how the recent developments are going to affect that, but we just hope that there's more support from the regulators. [00:38:17] Speaker B: Yeah. And you've kind of front run the next question, which is the magic wand. If you could change anything about how regulators work with you or work with biotechs. I'm curious, what's the top of your wish list here. [00:38:29] Speaker A: I appreciate that there's safety considerations and there's a lot of, a lot of important things that need to be met to, to make sure that, you know, we're not harming patients in any way. But I wish that there was just a speed to the communication because every month to buy a tech company could be detrimental. Yeah, they're, you know, just sitting there and waiting for a response for months, which is not within the timeframe that was indicated to you just can be quite detrimental. [00:39:10] Speaker B: Yeah, yeah, absolutely. You have a, you have Runway to manage as a biotech that maybe some of your larger contemporaries don't have as large a concern around. [00:39:20] Speaker A: Exactly. Yeah. [00:39:22] Speaker B: Well, Gina, I've so appreciated you taking the time to have this conversation. Thank you so much for being on the show. [00:39:27] Speaker A: Okay. Thanks so much for having me, Brandon. [00:39:30] Speaker B: Of course.