Derisking CNS Drug Development With Tortugas Neuroscience's Jeff Jonas, M.D.

On this week's episode of the Business of Biotech, Jeff Jonas, M.D., CEO of Tortugas Neuroscience, talks about the company's April 2026 launch and how in-licensed development assets were chosen. Jeff explains his strategy of chasing fast proof of safety and efficacy in humans, not animals, and talks about what product differentiation looks like in brain disorders, from adjusting indication targets to conducting head-to-head trials. He also reflects on the opportunity with psychedelics, RFK Jr.'s quest to curb SSRI prescriptions, the payer landscape in CNS disorders, and more. 

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Transcript

Welcome And Tortugas Overview

Ben Comer 0:03

Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Jeff Jonas M.D., CEO at Tortuga's Neuroscience, a company launched in April with $106 million in funding and focused on developing orally formulated formulated small molecule new chemical entities to treat central nervous system diseases with high unmet need. Jeff is a Harvard-trained psychiatrist and veteran of the CNS therapeutic space. He was behind the first FDA-approved indications for binge eating disorder at Shire and postpartum depression at Sage, among other products and indications. I'm excited to catch up with Jeff about his new CEO role at Tortugas and the company launch, what's happening in the CNS category more broadly, and what new indications might be on the horizon and what's coming next. Uh, Jeff, thank you so much for being on the show. Yeah, thanks for having me. It's good to see you again. Yeah, good to see you again, too. We

When Head-To-Head Trials Pay Off

Ben Comer 1:05

first met in New York City in 2012 uh for a feature story I wrote in Pharmaceutical Executive magazine on some work that you were doing at Shire at the time uh to expand the Vyvanse label. Um, one of the things that stuck out to me about that story was your real fearlessness about conducting head-to-head trials. I still don't see a lot of those trials happening. And I'm curious, you know, if most companies are are still afraid to go head-to-head against competitors, or or is that is that changing?

Jeff Jonas, M.D. 1:38

Well, you know, it's a good question because to some extent, people pick the studies that get approvals in whatever country or territory. So the U.S. doesn't require head-to-heads. So as a result for expediency and capital efficiency, a lot of us, you know, when we do drug development, don't but don't do that. I was a big believer with Vyvanse and differentiation back in the day, and it made a lot of sense. And of course, we did run the head-to-head against several agents, and it worked out very well for us. Um, sometimes your faith is not rewarded. But if you want to, the view is still that beyond getting approvals, how do you inform clinicians what the best way to use the drug is? And how might you then choose which agent to use, especially in indications there were multiple, multiple drug candidates to choose from? So I still like them. I think when you run a head-to-head, it's you get a lot of valuable information that informs the clinician how to use, and plus you inform the label a little more broadly. So I like them when you can get them and when you can get willingness to run them. I'm still a fan of it. A lot of that can be done in phase four. Sometimes academic centers can do that as well. One of the challenges is when you run a head-to-head, can you how do you can you use that to inform clinicians? Can it be put into the label? And I think we don't have really clear guidance yet for those kinds of that kind of information flow. And I think that's an impediment to doing more of these studies. So for example, right, so if you're if you have let's say you have you're numerically superior on speed of onset, can I make a label claim? So those are all impediments to doing that sort of proposal. But I'm still a fan of it. I still think it's important to inform clinicians and patients. So yeah, when you when you can get those data, uh, I think they're beneficial.

Ben Comer 3:25

Yeah, I mean, the willingness is a is a key piece. It's potentially a big risk. You know, you come out of the with the you know, with the findings of the a trial and potentially tell everyone that your competitor is better. You know, so you gotta have some you gotta have some belief in the product and uh and I guess be careful about how you structure. But I I was always uh I always admired companies that that did that. They're willing to essentially, you know, get behind their product in a really fundamental way. Yeah.

Jeff Jonas, M.D. 3:50

Well, you know, there are a lot of maneuvers that one can do when you do drug development. So for example, you first of all, we don't have a regulatory pathway really for like non-inferiority claims that let you make anything beyond a non-inferiority claim. So that's an impediment. But beyond that, you know, there are other maneuvers, like for example, in the antidepressant market, you do a switching study. So there are ways to get at it a little indirectly, but the head-to-head, you know, is sort of, I hate to use the phrase gold standard, but that's a gold standard way. If we had more regulatory guidance where we could advantage the products, that might open the door to more of those kinds of studies.

Leadership That Shares The Credit

Ben Comer 4:25

Uh I want to ask your uh about your time at Sage Therapeutics. Uh uh, you also worked with with Steve Paul again at Karuna, who had the very successful schizophrenia drug and uh acquisition uh by BMS. Um what uh what thinking back about that time at Sage, Jeff, you know, what accomplishments are are you most proud of?

Jeff Jonas, M.D. 4:48

Well, that's an interesting, it's it's I I always people sometimes ask, like, you know, I've I've had my name on a lot of NDAs and SNDAs in my career. And sometimes people ask that question. And I've reflected on this a lot. And one of my takeaways from having worked in the industry as long as I have is that no one person is responsible for an NDA or a clinical program. You know, it's really the it's it's a it's it's a product of a number of people of different disciplines, maybe hundreds of people across multiple disciplines, from the chemist all to the people who do manufacturing, the people who do clinical ops. And so sometimes people ask me that, and what I always say is I'm always proud of the teams I get to put together and the people I've worked with, not any particular product, although there are a lot of products I've developed and worked on that I'm very proud of, but really it's the people I've worked with and the people who've really executed for a common mission and a common goal, which is, and that's why this business is so great. You work with people to create a medicine that can benefit patients. It's just really, there's very few places where you can get that kind of scale to potentially benefit people. And so I'm always proudest of the teams I've put together and where I've either led them or participated, and especially when I see someone I've worked with or someone who's worked for me go on to do great things later on. So we had you know, and that's really the best part of this business for me. So it's really not the individual drug, but the people I've worked with over the years who've I've been able to help and who've helped me learn in areas that I, you know, that I wouldn't have otherwise had an opportunity to learn about. So that's how I view it versus um you know, versus you know, what product I'm most proud of. And one of the things I always say is leaders who need credit can't be leaders. You have to really want to embrace working with people and letting them grow and having credit along with you know all their teammates to achieve a common goal. So I I think that's how I look at my career when I take a moment to reflect, which is great teams, people I've worked with, people who have who've taught me things, and where I've grown and where I've helped been able to help people. So that that's sort of my perspective on that.

Ben Comer 6:52

And now you have a new opportunity to do that again, to build a new team at uh Tortugas. So you're you're back where you want to be, it sounds like, uh, in creating this, uh creating this new team and and pushing this this company forward. I um I looked back at the article from 2012 because I wanted to ask uh, you know, a couple of follow-ups uh from that, just given the amount of time that's passed.

Search And Develop Into Humans

Ben Comer 7:15

And uh one of the things we talked about back then, Jeff, was the search and develop model for R&D. And I was, I was, and you were, of course, at Shire at that time, but I was curious if that was a model that kind of stuck with you, if that was something that you brought to Sage as well. It was.

Jeff Jonas, M.D. 7:31

I mean, we had great chemistry at Sage, and I think that, you know, and my the president at Tortuga is Al Robichaud, of course, is uh came over from Sage as well. And the search and development, especially in CNS disorders, I think is crucial. And I think this gets to some of our, I think some of the things we probably will discuss or bring it up now, which is when you have pop disorders that are polygenic or disorders where there's where there are multiple systems involved, it's very hard to predict outcome based on animal data. It's just a very challenging dis it's very challenging to do so. And CNS in particular, especially when you're evaluating symptoms, not biomarkers, is is really one of the most difficult places to develop drugs. And and so that that really has led to this uh what I consider to be a pragmatic model, which is find target, get good chemistry. Uh obviously that's where we did a Tortugus, we have NCEs, find some good, make sure you get to hit the target, and that's where you can get some animal data. But then at that point, bring it into humans as quickly as possible to get your proof of principle and proof of concept. And you know it's it's it's something that's been with me, you know, as a I view it as biological experimentation versus bench experimentation. That's always been my bias. It's one of the reasons when we form Tortugas, we really focus on assets that were, as you described them so well, new chemical entities, but that were ready to go into phase two programs. And frankly, that's you know, you know, selfishly, it's not what I like to do.

Ben Comer 9:02

Right. Well, you uh going back to 2012 again, a longtime skeptic of animal models, uh, at which you've just spoken to, uh, you you mentioned it back then. I think I saw it in a press release on Tortugas as well. Mice don't get psychiatric diseases. Uh, but I, you know, I had to ask, and and I think, you know, the FDA too shares some of this belief. They seem to be really trying to scale back from or I guess push forward with non-animal models. Uh, there's a big, you know, initiative to do that at the FDA right now. Uh, but I I had to ask, you know, I know that Karuna, for example, used PsychoGenics uh mouse smart cube to great effect uh for their schizophrenia drug. Um, are you still a believer that you got to get away from mice as soon as possible? Or are there these new technologies, smart cube being an example where you actually improve the signals uh for preclinical research and psychiatric disorders?

Jeff Jonas, M.D. 10:00

Well, I think you can improve signaling, obviously, by looking at target acquisition, you know, pharmacokinetics, pharmacodynamics, and animals. But ultimately, I think what you when you're dealing with complex system diseases, I'm still a believer into humans more quickly. But if you want to take an analogous example, think of sickle cell. Here we have a single point mutation, and yet the manifestations of that disease are myriad. And you couldn't you couldn't predict pain, incapacity, disability, um, all the other things that people with sickle cell suffer from from a mouse model. And so that to me, that's the ex that's the challenge that you have in extrapolating beyond target acquisition, et cetera, going into humans, especially when you don't have biomarkers. So I still think it's challenging. I think look, Karina, I'm not saying you can't do it, and it obviously has worked, but I I think my preference is to moving into human testing as quickly as possible. We're always going to have to use talk, get talks data and basic safety data. There's no question. The question is, when does that become predictive? And when does it simply extend the pathway to getting into humans? And I think that's the conundrum that every drug developer faces as we screen competence.

Ben Comer 11:12

Yeah, absolutely. I was told on a recent episode of this show uh by someone that, you know, if you imagine chocolate is the most effective drug in the world and your, you know, your dogs are your test animal with the FDA,

Venture Versus Operator Views On Risk

Ben Comer 11:25

it's never getting approved. Really? The toxicity shows up. Um, I, you know, just uh one more question on your your background, Jeff. I was looking through your LinkedIn profile. It seems like you've had a lot of jobs, some at the same time. And I'm wondering, you know, you've been uh you know CEO at a company while you're director at other companies. I'm curious about how you manage your your time. How do you do uh how do you do all these things uh simultaneously and and how are you effective? One very important secret. I don't play golf. Okay. Hey, that's like a solid four or five hours, you know, right there in a single single round.

Jeff Jonas, M.D. 12:02

Uh beyond that, no, I think uh, you know, I've always been careful constraining my board work. I like doing board work in companies where I have a strong belief in what they're doing. I find that it helps me grow as a person, and I'd like to believe I can contribute. But usually I've always, you know, I think I've always had one central job, but I've I've been fortunate to be recruited for boards over the years. But usually I've always had one particular, you know, full-time role as I do now. Um, you know, most recently I moved out of the venture world, which I found interesting, a little different, and and back into operations, which I uh that's what I really enjoy.

Ben Comer 12:33

Well, yeah, I want to talk about that, and we'll we're gonna get into uh Tortugas as well. But what made you decide to join the venture capital world as a partner at Cure Ventures, uh, which was uh obviously an investor and I I think helped to form uh Tortuga's neuroscience. I'll ask you about that too. But what what decided what made you decide to to get into that side of things?

Jeff Jonas, M.D. 12:57

Well, you know, when it comes to financial issues, what do they say? It's always better to give than to receive. And, you know, uh there's a lot about the venture world which I really enjoy. And Cure was a great place for Al Robichaud myself to join. They were pretty agnostic about indications. They were supportive about looking for assets. I can get into that in a minute. But my experience on the venture world, you get a lot of variety, you get a lot of different inputs and things to evaluate. So I could be looking at a T-cell engager one day, another day I can be looking at CNS where I have a lot of familiarity. So that is it's very intellectually stimulating, and you get to be on the ground floor of building things. What I found to be differentiating, and one reason I like operations, when you're on the venture side, you're looking at risk and probability of success, and you're trying trying to prognosticate that. And this is not to be demeanative, uh demean uh negative, but it's sort of like being the coach of a fan of a fan football league. You get to opine, you get to say, well, am I gonna win or not? But you're not on the playing field. And I think this, I think there's a lot of appeal to being an expert and and being articulating and looking at risk. But I like being on the playing field, I like operating, and I like I enjoy working with people to look at the risk and to try to design trials and programs that get us to the goal line. And that's and so I, you know, it's it's I think it's a different, it's a different viewpoint. And you know, venture capitals are about assessing risk, and operators are about dealing with risk. Right. And I like dealing with risk. I mean, it's risky. Um and you sometimes get an answer you don't like, but you know, that's part of life and it's part of the challenge of doing of running companies.

Ben Comer 14:41

Do you think company operators are are kind of by nature uh more less uh risk averse uh than than the VC crowd? Oh, no one likes to fail.

Jeff Jonas, M.D. 14:51

I mean, everyone says you learn from failure, but if you learn from too much failure, that's not a good thing. Um I I think it's I'm not sure it's risk aversion. I think it's more the ability to tolerate risk and the ability to strategize around it. How do you mitigate risk? And I think that's a different, a different skill set in assessing risk. And they both have extremely important parts in the biotech ecosystem, but I do think the mindset's different. Someone who's never, you know, again, I'm a biased, I'm biased because I've treated patients. Someone who's never treated patients has a has a different view of how how to evaluate an adverse event profile than someone who's worked in a lab and is looking at an AE table. And I think that's it's a diff it's a different mindset and a different skill set.

Ben Comer 15:36

Uh let's talk about the the Cure Ventures model

Building Tortugas And Choosing Assets

Ben Comer 15:40

uh for company building. What does that look like? What kind of uh I guess criteria do they use when they're thinking about assets? Uh and you know, what give me a sense of the process for you know how a company starts that's backed by Cure.

Jeff Jonas, M.D. 15:53

Well, I mean, so Cure obviously, you know, we're a smaller company, and one of the things I like most about Cure is they took in enough money to be meaningful, but not so much that they had to do something. I think that was a very important sweet spot that the founders of Cure were able to achieve. Um we do we do a lot of work on preclinical work, a lot of genetics. We did we have a great genetics group as well that look at things like feasibility, clinical profiling, and and disease profiling as well. And we're pre-A typically. Um Tortuga is in some ways is a bigger swing. Um and they, you know, we we I think we're not very different from other firms. We have, you know, we we look at opportunities. We have a big Monday meeting where we speak, everyone goes, we talk about all the opportunities, trying to make decisions, and then you know, we look at the finances, valuations. That's pretty standard. I think the differentiation is a lot of focus on on incubation, a lot of focus on management, and a lot of focus on genetics and scientific foundations for investments. And that that I think is probably our our you know one of the differentiators for the firm. Plus, having a quantum of capital that gives us the ability to invest wisely, but doesn't say we have to deploy, we have to deploy, um, which I think lead can lead to uh preemptive decisions potentially.

Ben Comer 17:10

Um Tortugas launched, I think, with 160 million or excuse me, 106 uh million dollar um uh series A plus seed money. Um so once once Cure decides we're gonna we're gonna form a new company, what do you think is then the most challenging aspect of of the startup and formation? I mean, is it is it staffing, which is something that you've talked about that you enjoy doing? Is it uh is it you know, drug candidate selection? Is it uh getting the you know, um, I guess the next round of funding in the door? What would you say is is the most challenging part for you? Should I say all of it? Yeah, that's yeah, you could say that.

Jeff Jonas, M.D. 17:49

Yeah. Well, we were fortunate when we started, you know, Cure gave us backing. Al and I joined about two years ago now, I guess. And we were, we when we joined, we started getting inbound inquiries for us to participate in development candidates. And we decided we wanted to look develop a program for central nervous system disorders. And we went out and looked at more than 120 assets, and we had a particular bias of what we wanted to achieve. We had some mechanisms we liked and some we didn't like, and um, you know, we all have our intrinsic preferences. Um and we ended up locating assets from Hansoh and Eisai that were that actually fit our profile pretty precisely. So we wanted new chemical entities. That was very important. We're interested in platforms or reformulations. We wanted to go into larger markets or specialty markets, and we wanted mechanisms that we thought had some level of de-risking, either preclinically or even clinically, and where if we had some signaling or positive findings, we each asset could be expanded into multiple indications. So we wanted extensibility of each asset across indications. We were also focused on CNS because that gave us a lot of operating leverage, because we have a lot of familiarity with that space. We were able to recruit people, you know, although we're pretty lean right now, who also had familiarity. So we could go across indications without having to hire discrete teams for each for each potential indication. So that gave us a lot of capital efficiency. Beyond that, we were fortunate, you know, Hansoh and Eisai had programs we liked, and we actually approached them for their programs, and we were able to license them in. You know, both were very active, so we were in stealth for quite some time while we formed it. Um Tortugas uh was formed really with you know with the help of a column group and cure, and then you know, and they took a sort of interesting attitude which we liked, which was Al and I had experience bringing drugs to market, so they had some faith that we knew how to do it again. It was we hadn't done it once or twice, we'd done it several times. Al had a history of very good chemical invention, and so they formed helped us establish this. We were able to do the licensing deal and then close that round. So that it really evolved naturally, and it was a pretty classical case of company incubation where we had a small group, we brought in the assets, we did the due diligence, we did the licensing deal, but they were very favorable. We we haven't really put out those terms publicly yet. Um we're enjoying being private. And um and so we had great support from them. And then, you know, with the with the with the addition of AN Ventures, it gave us a really good core group of investors. And for us, once I put my CEO hat on, we had investors who understood the CNS market. Very important. You know, there's really nothing quite like the CNS market. I know you'll ask questions about it later, uh, in terms of how it's structured and how products have to get approved and studied and approved. It's very distinct from, say, cancer and on one level. On the other hand, there is commonality. We all talk about remission, we all talk about time to relapse and things of that nature. So there are commonalities. But at the end of the day, we have four of these four assets, they were all unique. And we were able to, as we acquired new data, to really position them into areas that we thought they could either be unique and first, first in indication, or first in class, or potentially better in class. I don't want to say best in class because that's a little hyperbolic, you know, better in class because that's the way the world works. And so we each of the assets has one of those profiles, and they're all independent, independent mechanisms. And for those of us who've been around, if two or three of them work, then we have a big company. Because each of them have multiple potential indications. You know, if we get lucky in all four hit, okay, we'll be even bigger. But you know, we have a portfolio, and I hate to use the phrase multiple shots in goal, but that's what we have. And they're all independent of each other, which is very important to us. So we maximize the chance of success.

Ben Comer 21:43

Uh that's excellent. Um, I I wanted to ask just about uh you you talked about these uh these products, um, not well uh what's the phrase that you used? Uh um there there's not as much risk uh w associated with these uh with these. Particular assets. Can you give me a sense of like what those attributes are? De-risk. I can't think of the word. What are some of those de-risked attributes about these candidates that you like?

Jeff Jonas, M.D. 22:12

Well, I mean, so all of them have been through phase one testing. So that's part of it, yeah. Right. That's part of it. So we don't have any major red flags there. So that's nice. We all have we have compounds for the clinic. So now what we're doing, we move it, we're moving API over, we're setting up for starting studies. So a lot of that early risk is gone. So we're not having any, you know, we're not in the middle of an IND and we we have, you know, some major tox finding. So that's all done. So all of them have been in the clinic, and we are, I'm not saying we're repurposing it, but we're some of them are redirecting. Or at least one or two of them are redirecting into areas where you think they have a much better probability of success and where we think they could be positioned more actively. So by example, the hand, one of the Hansoh products is a neurosteroid, which you know we've worked with before. And it happens to have a profile that we like. Um, it could be, you know, people are putting them in mood, as you know, but

Tinnitus Epilepsy And Encephalopathy Bets

Jeff Jonas, M.D. 23:05

it has an interesting profile, slightly longer half-life and more potency than what's available today. Um, we recently saw some data for the IV formulation, uh, the IV formula, an IV formulation that has a similar mechanism that worked well in tinnitus. And I I've actually been involved with studies in tinnitus in the past. I was on the board of Decibel, and when we were at Sage, we were very interested in tinnitus, but never could get to it. So we all of a sudden saw these data, and it was very compelling. And so we said, you know what? There's an area of unmet medical need. Millions of people have it, nothing works for it. Most of the approaches have involved the middle ear and peripheral, that's old thinking, uh, on peripheral, uh peripheral mechanism, where I think modern thinking views tinnitus as if they almost like a phantom limb phenomena because of loss of external input from the ear, and you and you have cortisol activation in the auditory cortex. And it's and if you look at the symptoms of tinnitus, this is why it's fun to be a private company. Not only do you have loudness and annoyance, which is what most people get checked for, but they you also get insomnia, anxiety, and mood symptoms. So we have a centrally acting neurosteroid, and we thought this might hit the entire syndrome. So we were able to say, and that got tremendous investor interest, frankly. And so we repositioned the drug, and and we and we said, and we can we know how to do the study, it could be done very rapidly to replicate it. So that's the kind of thing we were able to do. We then, the other, that's a Hansoh program. The other program that came from Hansoh was a D2, D3, 5-HT2A. So Al Robichaud was literally the fellow who synthesized Caplyta. So I shouldn't, I'll just say that. And I did the early work on Vraylar when I was at Forest Labs. He knew this phase very well. So we're still waiting, we're still waiting for some phase two results from them. But we looked at the profile that Hansoh drug had and said, you know, this has the potential to be commercially differentiated. Not unique, but potentially differentiated from Caplyta and Vraylar and other competitors. So we'll see what the 2B program looks like. If it's strong, and we think it could be based on what we've seen from the preclinical data, that's where preclinical data work. But we have to see the clinical data. If it works, that could be a very important drug for schizophrenia and mood. We got to wait for those data to be revealed. If they are, that's where we'll put it. So that's the kind of flexibility Cure gave us, and that's the flexibility we have because we knew the space pretty well. The Eisai compounds, um, we had, you know, one is an uncompetitive GAT-1, which makes it very different from what's out there. We know GAT-1 is a validated mechanism, but this is one that's circuit selective because it's uncompetitive. And so it may have a better therapeutic index than prior GAT-1's, which may make it more active for focal epilepsy with a with a better therapeutic index. And for that one, I'm going to retract my comment on preclinical data because we know in epilepsy in particular, pre-clinical preclinical data are pretty reliable predictor of activity. We have that for the GAT-1. And then we have a centrally acting PD9 from Eisai that we're very excited about because it has really good activity and increasing CIPA TMP levels in the brain. We know from a lot of animal models, again, I'm taking back what I said, that that could enhance cognition. We think that those kinds of drugs need to be positioned in people who have intact neuronal substrate. Not severe patients like with late-stage dementia or frontal temporal epilepsy or late-stage Parkinson's, where you already have impaired neuronal activity. It needs to go to areas where you have good neuronal activity that may be transiently suppressed. So that's why we're going into encephalopathies. So that's the kind of stuff we were able to do. But all these drugs have been tested one way or the other. We think they can be repositioned properly. So that's the opportunity that we have. And you know, cure, you know, our investors now are are believers in this approach, which is very pragmatic, which is going into humans, getting a signal, and then moving forward. And then you can see how each of those potential and so if you take encephalopathy, we're going into hepatic encephalopathy. If we get a signal there, we might go into uremic encephalopathy, postviral encephalopathy. So we can extend it with a powerful signal or positive signal. So that's, you know, I think that's the kind of thing we're doing to develop these molecules. That's what we do when we incubate. We do have, we also will do at some point some early discovery work because, as, you know, when you look around and look at assets, we have a very strong group of medicinal chemists, and we'll see a target, and someone will see chemistry. And our chemistry guys say, uh, we can make a better drug than that. I have to restrain them for now. But but we do have some interesting preclinical targets as well that we'll be targeting.

Ben Comer 27:44

Um for Tortugas, uh, when you were searching for uh these candidates, two from Hansoh, two from Eisai, were you limiting the the pool of potential uh uh targets to license to small molecule oral formulations only? And I think correct me if I'm wrong, all four of these you are developing as an orally formulated uh tablet, uh maybe daily administration, or I don't know if you've decided that yet. But um, if you did, you know, limit the criteria to small molecule oral formulations, what what's the reasoning behind that? Why did you uh why did you want to keep it in that category?

Jeff Jonas, M.D. 28:21

Firstly, I like ease of administration. And you know, I come out of having been a clinical person. Um, most of these are likely to be uh once daily medicines. I think that's important. Um we wanted to look at NCEs, and we thought, and all of them have the potential to be formulated differently. So we have a very good, we have a very good group of CMC people we're working with. So you can imagine like we had at the D2, D3 to be work where we were to be active in a way we like, you might make that into an IM, for example, or a patch. So that all of them can be reformulated, but we liked starting the small molecules. Yeah, you don't, you know, supply chain is straightforward, synthesis is straightforward. It's easy to develop backup suppliers. So those are all things we liked. And it turned out opportunistically, based on the mechanisms we wanted to explore, that we found small molecules that had good patent life.

Ben Comer 29:11

Um Eisai is uh obviously a Japanese company. Hansoh, though, is a Chinese company. There is uh uh you you can't get away from conversations about uh innovation in China and the Chinese biotech sector. Right now, there's just uh there are new deals being announced uh every day uh with Chinese biotechs. And and I wonder, you know, what you make of that, Jeff. Uh you know, based on your experience in the industry, you know, what what I guess has changed about uh China and the Chinese market and the the biotech environment there? And you know what I guess uh what are the implications for maybe the CNS category specifically?

Jeff Jonas, M.D. 29:51

You know, when I used to treat patients, I really never cared where they came from. Yeah I just wanted them to get better. And I feel the same way about drug candidates. And go where the sciences. Go where the sciences and and the you know, I I'm trying not to be too provocative. Hansoh is a world-class organization. They do great chemistry. Um, they did a good job in their synthesis on both of the molecules we had. And if there's a problem, it's not with China, it's with the U.S. And I think it's up to us to compete. I mean, that's what this is supposed to be about. That being said, we're gonna bring these assets to the U.S. We're gonna study them here, market them here, we're creating U.S. jobs here. So I think this is an opportunity for for entrepreneurs in the U.S. to really build business and opportunities here. Um, but you know, China, you know, you know, has taken you know, has prioritized doing this kind of science. Um, I think that's an issue that we have to, how do we become more competitive again with this? At the same time, and you already know this, people are going to China because they have good assets. And we're not the only ones. Uh, you know, a lot of majors have what have done as well, because they they they can do excellent science. Um and if you look at clinical trials, most of the most of our clinical scales, especially in psychiatry, have been validated in Cantonese and Mandarin. They know how to run trials. Um, so you know, the obviously the politics, which I won't get into, but I think if we talk about you know competition, we're we should we need to compete. And but right now, if I can get a good drug and develop it in the U.S. and create a company in the U.S., I'm happy to do it.

Ben Comer 31:30

I want to uh next step back a little bit uh and talk about innovation

CNS Breakthroughs, SSRIs, Psychedelics And Payers

Ben Comer 31:35

in CNS therapeutics. You've worked in CNS therapeutics uh for most, uh, if not all, of your professional career in the life sciences industry, Jeff. Um, what would you say has had the biggest in terms of innovations, what do you think has been the biggest impact uh during your time in the industry in the CNS space?

Jeff Jonas, M.D. 31:57

That's an interesting question. I don't let me think about that. The big well, it really depends on the phase. So you think about this, it really depends on the phase of introduction. So what we were had when when we had it. So one can argue the advent of chlorpromatine had the biggest impact. It was the first time people really thought about psychiatric medicines that way. But remember, you know, remember at the turn of the century, laudenum was used to treat melancholia, right? So people have always tried to alter moods in different ways because we recognize that there are mental conditions that are are impair normal function. Hold us back, that's right. I I think probably in my, if I were gonna say one one ad one thing that probably changed everything is probably the advent of the SSRIs, which really brought the treatment of depression, uh, probably moved it from psychiatry into the primary care market. I think the SSRIs, the easier to use, didn't have to get blood levels and so forth. I think you can argue that led to the democratization in a great and great extent for the treatment of depression. I think you know, with the safety profiles and so forth. I think it had a had a branch of an unfortunate side effect of putting to the side drugs that were very effective, like MAO inhibitors. A lot of psych residents don't. Um J. Clynn Cyclofarm had a really nice editorial about this a while back. Uh Anthony Roth Rothschild wrote it, where he talks about a lot of residents today don't use lithium. They don't use MAOIs because it they're cumbersome to use. And the so I think the SSRI is probably the biggest first, and then I think the atypicals are the second. Yeah. The advent of the atypicals. Um, and probably because it is it used in pro to some extent, maybe better efficacy. And you know, and and I think those are probably the second big, especially in psychiatry. I think those are probably the two big, the two big areas. I think the the downside has been a lot of follow-on compounds that may not have been beneficial, you know, or or have marked superiority. Um, and that that's probably a different a different area to discuss. But I think a lot of the uh the especially the SSRIs and the atypicals, I think what's happened is mental health disorders have become destigmatized. People could go to their GPs or internists who prescribe most of this in psychiatry, in particular for depression, and be treated without the stigma such as it is of going to a psychiatrist, et cetera, et cetera. So I think those are the uh probably the biggest changes that we've seen right now. I think the last I'd argue are are the stimulants for ADHD. That's probably the other major change. Uh, you know, we can we can have a discussion later if you ask about how it gets diagnosed and diagnosed, but there's no question that, you know, people who with ADHD benefit from the had benefit from the use of those drugs.

Ben Comer 34:44

Absolutely. And millions, I think it's fair to say, or uh, you know, millions and millions of people have benefited from SSRIs. And uh, you know, you mentioned that as a key innovation. So I have to ask, you know, what you think about RFK Jr.'s uh uh suggestion or or now initiative to reduce over-prescribing of SSRI medications. Do you think they're over-prescribed? Is he onto something here or or dead wrong? What do you think?

Jeff Jonas, M.D. 35:12

Well, firstly, I think we should make one major comment here, which is and you just said it, millions of people, not thousands, millions, have benefited from the use of psychiatric medicine. Absolutely. That is a gold standard piece of science, and it's beyond dispute. So that's number one. And people don't say that loudly enough. I think people read Twitter, which I don't, um, and you know, people like to complain on social media because that's who why else be on social media. Um, and so millions of people. And I think that is one of the major advantages that we've made uh this century and last century. And secondly, it these drugs have helped destigmatize the treatment of mental health disorders. People have been benefited, they've gone back to work, they've they've gone back to their families. You cannot overstate how important they've been to the health of Americans. Now, that being said, I think you know, there, you know, we've uh one of the challenges is that they are used broadly, a lot, a lot by, you know, I don't want to cast a spurs by primary care and people who aren't psychiatry, which has broadened the use of these drugs. And there are proper ways to withdraw these drugs from people. Um but it is confusing to separate we uh relapse from withdrawal syndromes, which is why most of us who've used them in the past do very slow withdrawals when we take people off the drug. But we know that SSRIs are very effective, maybe more effective in maintaining mood than they are even treating acutely. And so it's not surprising that there are people who relapse when the drugs are withdrawn. So that's a that's something we have to parse out over time. The people probably can withdraw more carefully, but you know, you know, the the the last piece of this, this is an old canard, and we've heard it with benzos, we've heard it with other drugs, that somehow these drugs enhance disinhibition and violence. There's just no evidence for that. That's that's simply pharmacomythology. Um you know, it for the same people, and I think the you know, can we prescribe better? Yeah, that's true of every drug and every class of medication. But I don't think it helps people to stigmatize mental health. And I think that these drugs have been a major advance in healthcare. It's you know, the leading cause of workplace morbidity remains major depressive disorder. This is something that's important for Americans' productivity, our economy, and we need to, you know, perhaps we can do better prescribing, but calling for their cessation is a mistake. And we all remember the epidemiology after the black boxes came out for teenage use of SSRIs, and and and we saw an increase in adolescent suicide. And I think that's something we have to proceed with caution before castigating a whole class of individuals as well as medicines. So, again, that's my piece on that.

Ben Comer 38:02

Yeah, absolutely. Um, I asked you about the biggest innovations in CNS. I wonder uh what you might think about the biggest areas of remaining unmet need, Jeff. And I I may be attached to that, I wanted to ask you about psychedelics and the the impact that they might have on um on patients with mental health disorders.

Jeff Jonas, M.D. 38:22

So, first, I I think that you know, not everyone gets better with depression. We all know the star D study. We know there are good maintenance studies, long-term studies, and so forth. Not everyone gets better. So we can do better. Clearly, we can do better in depression. You know, we need new mechanisms, no question. Same thing is true with schizophrenia. I mean, the beauty, you know, the importance of Cobenfy was this innovation. You know, I was on the board of Karuna, full disclosure. Yeah. Um, but that was very important. You know, can we improve on Cobenfy? May people will will be no doubt we'll be trying to, right? We'll see more M1s and M4s, and and but this is another area of unmet medical need. I think clearly where no one has ever touched are the personality disorders. And if we go back in time, which most people don't want to do, if you remember, it I'm gonna digress and I apologize. Yeah, go ahead. If you recall, when we had when the DSM one came out, I think there were maybe a hundred diagnoses. What year was that, the DSM one? 52. Okay. And today the DSM five, so it was and it was about a hundred pages. Today the DSM five is uh has 300 plus diagnoses in more than almost a thousand pages. Yeah. So one of the challenges we have in innovation and looking at unmake medical need is this proliferation of diagnoses and and how many diagnoses we have. If you go back and look at, again, this is historical. If you look at the Feiner criteria or Goodwin and Guzet, their position was you can only make a diagnosis if they were if you had some sort of family history validation, not only reliability, but some sort of biological validation, genetics, pharmacological response. And I believe they had they thought they were only 14 diagnosed categories. So this is a philosophical debate. So, but there are areas of unmet medical need, and I think the biggest one is I'm alluding to that's never really been broached in all this time are the personality disorders. Right. And we know they run in families, and so you have borderline sociopathy and things of that nature. That's a major opportunity for people for some to take care of. Um, I think the other area in terms of population, I'd say veterans care and PTSD is a major area that we need more innovation. I think you're gonna get to psychedelics in a minute. Um, it's a major area. We could talk more about that. You know, and I but I I think we have a long way to go before we have cures. And of course, the other thing we don't have in psychiatry are real biological markers. You know, right? You know, when you know, we don't have it. Now, there are probably a lot of reasons for that, but that's another challenge that we face in innovation where we have unmet medical need. Um I'm not sure that answers entirely.

Ben Comer 40:58

But well, no, does the is the science progressing on psychiatric biomarkers? Is there any new research that's impressed you in that particular area? I know it's obviously extremely difficult, multifactorial, a number of reasons why it's so difficult to come up with a reliable biomarker and a CNS disorder, but uh what where's the science on on that?

Jeff Jonas, M.D. 41:18

We've looked at a little bit of that, and I and I think um people are looking, and I I don't want to name companies. We have we have a program that's looking at an omics approach. Um other people have looked at uh pharmaco. I'm an I'm not a believer in pharmaco-EEG for lots of reasons. And I often say, you know, looking at EEG is like flying over New York and looking at the lights and trying to understand what people are having for dinner. Um it it's a it's a network effect. But you know, probably someone will come up with something. But remember, there are diagnostic requirements and then treatment response. So if we could predict a treatment response, that would be good. And maybe that's where we have more opportunity than in diagnostics, because probably we can't agree on diagnostics, which is probably the major, the major problem. And I used to I was on some of the DSM3R workforces, and uh one of my colleagues once said, if the Lord came down and gave us a blood test for schizophrenia, it wouldn't work because we couldn't agree who to try it on.

Ben Comer 42:18

Well, uh I'll let me rephrase my question on on psychedelics. Uh what you know, what what is the size of the opportunity there? I mean, do you I I think you do you expect them to get approved, you know, in the short to medium term? I guess I'm talking about classic psychedelics, uh psilocybin, uh, IBogaine now is a kind of renewed interest in that, LSD, DMT, MDMA. Um, what what is your uh your feeling, I guess, in terms of the opportunity there? What do you expect to see happen?

Jeff Jonas, M.D. 42:48

Well, there's a little bit of conflation with the political question you just asked, which is how do you enhance access to treatment? How do we get people to see get treatment for mental health disorders? And are there ways to achieve that without placing people on chronic medication? And I think that's that to me, I'm framing it that way. I don't want to get into specific mechanisms. I'm a little conflicted here, as you know, because I sit on the board of compass and I'm very excited about that company. Um, and we know that they, you know, they got a priority voucher. So if you just look at the broader landscape, what what's the promise here? And that is, can you get people better more quickly with a single or single treatment or two treatments in a way that doesn't enroll them into the mental health system? And I think if you can do that, that would go a long way to to reduce stigma, to broaden access to mental health care. And we know that's a problem. It's hard to see a psychiatrist. I don't want all my friends to be mad at me, but it's it's hard to get it to see psychiatrist psychiatrists. Absolutely. We know that the vast majority of people who are who are depressed are being treated, you know, not by psychiatrists. We have a tremendous issue with PTSD, with veterans and other. People with traumatic events and the ability to treat people quickly and acutely without the need for chronic medication is a great promise. And I think that's an area, that's a potential area of real innovation. So I'm optimistic that will work. Will I, you know, I obviously have my favorites, which I won't say anything publicly. Um at times who I think, you know, have the best shot. But I do think this is that's if you look at this from a societal standpoint, that's where I think why the idea of psychedelics are so promising. Beyond the novelty and you know, how cool it is and all the kind of things we want to talk about, and celebrity influences who we could all live without, the idea of getting people better faster, more quickly in a supervised setting, and then letting them go back home to work to their families, it's extremely appealing. And that would be an important breakthrough for people.

Ben Comer 44:49

Do you think the payer landscape is set up for this, you know, treating CNS disorders uh in a non-chronic type of way? I mean, is is are big changes going to have to happen with with payers to you know to promote you know wide access to these therapies or you know, um relevant access to to patients?

Jeff Jonas, M.D. 45:09

Well, I'll say payer innovation is uh is an oxymoron. Okay. They they are naturally conservative, right? And they want to see benefit. So it'll be up to people to say, why is it beneficial to keep people out of the mental health system? Can these people go back to work? Can we unencumber them from other kinds of care? Maybe they can be monitored by an app. There are other ways to think about this. And so I think ultimately payers will will need to come around. They may not want to initially, and then the question is gonna be is we face this with PPD. Do you step edit someone with an unapproved drug or make them go six weeks to six months before you give them something that might work in a matter of days? How do you justify that? And I think that's gonna I think that payers will ultimately come around. I think the pharmacoeconomics will support this kind of approach. I think it will broaden the prescribe prescriber base beyond psychiatrists, and that'll be very interesting to see how that happens. That may make it some way even more cost efficient. So these are things that I, you know, I don't have an answer to. I think ultimately the payers are naturally conservative, but I ultimately believe that if these drugs show a benefit, that they'll need to come around. Then the question will be are if you're going for treatment-resistant depression, of course, that requires a run-in. But as some of these are are approved for depression, it's actually going to create a different kind of conundrum for payers.

2026 Priorities, IPO Path, And Closing Thoughts

Ben Comer 46:36

Yeah, absolutely. Um, we are uh starting to run short on time here, Jeff. Unfortunately, uh I feel like this conversation could go on much longer, but I I want to just ask about your your top priorities for Tortugas for the rest of 2026. You uh you covered the you know the four initial assets that uh that you're developing. Um, what are you most focused on right now? Uh, I guess for the rest of this year. Well, we love all our children.

Jeff Jonas, M.D. 47:01

Yeah, right. Um so we'll we know we have some data. We haven't made a lot of this public yet, so I apologize. Again, love being private. Um, we have a number of card flips and catalysts coming out this year and early next year. And the results of those, and potentially some data, and the results of those will help prioritize what our next big moves are. Right now, we have enough to get through our major catalysts with with most of our compounds, and that maybe include signal finding, maybe release of some double blind data. So that's what we'll be looking for this year and early next year. And again, we're fortunate, you know, we have a lot of operating leverage and content leverage from people who've done this before. So we have a really good team of people now who are operating. So we're very excited by it.

Ben Comer 47:44

Um, you love being private. You've mentioned that. Uh do you have a is there a path to IPO? Oh, you know, are you looking, you know, like how what how are you thinking about the IPO market right now?

Jeff Jonas, M.D. 47:54

I only like being private today.

Ben Comer 47:56

Okay, yeah.

Jeff Jonas, M.D. 47:57

No, I I think there's a path. I think we have a path. Um, you know, you know this. We have a lot of potential pathways for this, depending on how our capital shake out. I I be, you know, I I you know, I love I I enjoy being a public CEO. I know that's a little counterintuitive for many. I enjoyed it. I, you know, I like working with the sell side and the buy side. They're a lot of fun people. Um it's a great opportunity and and you know, it's a real challenge. And you know, you do get, you know, the reality is, and this is true, of course it's true because I'm saying it, it whenever you have a catalyst, you get you you really do get better, more up typically more upvaluation when you're public than when you're private. Because the market speaks. So there are a lot of opportunities and a lot of advantages to being public. I'm not going to commit to what we're doing now. Right now, we're we're keeping our nose to the grindstone and executing on our near-term milestones.

Ben Comer 48:44

Well, last question are Are there any new, brand new CNS indications that you're thinking about right now, Jeff? I know you're probably always kicking around some new uh indication ideas in your head. Um, but uh is there any that you're thinking about right now? Any that you would potentially pursue at Tortugas? Yes. Okay. I'm gonna leave it there. Yes. All right. Uh Jeff, thank you so much for coming on the show. It's a real pleasure to reconnect with you. It's great to see you again, and thanks for having me and taking the time. I really appreciate it. We've been speaking with Jeff Jonas, MD CEO at Tortugas Neuroscience. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out our weekly video casts of these conversations every Monday under the Business of Biotech tab at lifescience leader.com. We'll see you next week, and thanks as always for listening.