Gain Therapeutics: a first-in-class, disease-modifying therapy for Parkinson's

0:05Hello, and welcome to Beyond Biotech, the weekly podcast from La Biotech. I'm Dylan Kassane, and this is episode 208 for the podcast. Today, I'm delighted to welcome Gene Mack, President and CEO of Game Therapeutics. With over 25 years of experience spanning biochemistry, Wall Street analysis and biotech leadership, Gene brings deep expertise in capital markets, strategy and drug development. He joined GAIN in 2024 and stepped into the CEO role in early 2025. GAIN Therapeutics is a clinical stage biotech pioneering next generation allosteric small molecule therapies. Using its proprietary Magellan platform, which combines 3D structural biology and physics-based modelling, the company is unlocking novel treatments for challenging disorders.

0:58Their lead candidate is advancing towards phase two as a potential first-in-class disease-modifying therapy for Parkinson's disease, with promising phase 1b data showing biomarker improvements and functional benefits. In this episode, we'll explore Gene's journey, Gain's innovative strategy, the Parkinson's landscape, and the future of AI in biotech. Gene, welcome to Beyond Biotech Thank you, Dylan Nice to be here Gene, walk me through your early interest in biochemistry How did it shape your career? How did you get into the life sciences? Yeah, so Okay, the origin story I guess that begins Kind of with some curiosity around medicine I owe family members A fair amount of family members who are physicians It seemed to be one of the more respected Avenues to take if you want to respect, you know, in the Mac household.

1:54So I slowly gravitated over medicine, strongly influenced probably by my older brother as a cardiothoracic surgeon. I went to undergrad, I went, you know, undergrad and did, you know, I enjoyed biochemistry, I enjoyed the science, I moved further into it. I wanted to be a neurosurgeon when I got out of undergrad and prior to medical school i did a um a research fellowship uh hybrid kind of thing at columbia university in their department of interventional neuroradiology big mouth style these are basically guys who did um video uh and contrast imaging of the brain and the cerebral vasculature um and the department that i worked for mainly tried to diagnose uh these um arterial venous malformations, horrible networks of malorganized vasculature in the brain that could be leaky and bleed and create all sorts of neurological deficits for patients.

2:50So we were on the cutting edge of that about 30 years ago at Columbia University, maybe about five or six guys on the planet could do what this department could do. So we got patients from all over as well as, you know, in Washington Heights, New York, you're dealing with gunshot wounds too at some point. And I was in the room a lot of times during operations because we would, the department I worked for did all kinds of clinical trials and was doing all kinds of studies, some for devices, some for their own publication purposes. So a very, very big diversity of research interest in an operating room in neurodegenerative disease and cerebrovascular disease.

3:27So it was exposed to a lot very early. what I learned is medicine's fun, but very difficult. And beyond dealing with, you know, your day-to-day patient interaction and just treating the patient, just trying to get, do what's best for them. You've got administrators all around you telling you what you're doing is not the right way to do it. And I mean, you know, think about being one of a handful of folks who could do what you're doing. You got this 25-year-old hospital administrator telling you you're using the wrong catheter on the patient. I just, you know, in your mid forties and fifties, after all the investment.

3:56So after about two years of that, I kind of came to grips with the reality that I was extending this research thing and continuing to push off and continuing to defer my medical school admission. So I was continuing to push it off. And so finally, I had a heart-to-heart with a couple of the physicians that were like, this is just not for you, and I love the research. So without knowing what to do next, I actually fell in with an investor relations because here I was, you know, 23, 24-year-old kid with a biochemistry degree in the mid-90s. I'm thinking I'm going to be out on the street if I don't figure something out soon.

4:36So I fell in with an investor relations firm who basically had me taking scientific principles from small pre-IPO companies and distilling them down into something that was a little bit more digestible on slide decks and pre-IPO messaging and positioning and helping organize strategy around companies going public. Very, very, very good education there as well. And in the meantime, I came across these things called analyst research notes. So these things would come off the fax machine every morning in the IR firm. And it was from all these banks, right? These analysts who were writing these recommendations based on research that they read.

5:14And they had degrees and they knew the science. And they also understood the interface of science and technology and drug development and capital markets and raising money and spending money and so forth. So this all became really intriguing. And we all hung on all these guys' opinions. Again, mid-90s, early 2000s, that's kind of where I was doing this. Analysts were, it was an exciting thing to do. You wrote your opinion, put a price target on, and you got paid lots of money for that. So I was like, OK, I want to do that. So I went to business school, found my way around a balance sheet, got recruited to a Wall Street firm probably in 2000 and then published research for the next 15 years.

5:50So it was kind of a combination of things. I think, you know, I really enjoyed the I really enjoyed science. I really enjoyed research. I really enjoyed the idea of testing a hypothesis in all sorts of ways. Right. And I kind of talk like this, too. Even in my kids, it's something you don't really divorce yourself. Here's my hypothesis about how you're behaving. Are you going to prove me right? Are you going to prove me right? You know, it's that kind of thing. So anyway, the discipline was there, but the desire was not. And so, you know, Wall Street led me down this path. And then after years of being an analyst, I kind of wanted to have a bigger impact on things.

6:27So the way to do that is to have an operating role. So here I am in biotech. So that's the origin story, more or less. So you jumped across to biotech. You were a CFO at several biotech firms. And I noticed that at least one of them was acquired by Merck. You never had that temptation to make that big jump to Big Pharma? Yeah, so that's an interesting story as well. So 2020, we're in the midst of the COVID crisis. A company that I was working for, OncoImmune, had developed a treatment for patients that were on oxygen support. So this is, in fact, this is not a vaccine. This was patients who were already having, that needed oxygen support and were going down that slippery slope.

7:12This was something that proved effective in getting patients off of oxygen support. And it actually showed not statistically significant, but in a small trial, we had a mortality benefit as well. So Musaf Slawi at the time was heading up at the first Trump administration. Musaf Slawi headed up the Operation Warp Speed project, where it was like a coordinated effort to get anything that worked even reasonably useful as a countermeasure to COVID would get some serious attention from it. So we talked to everybody in large pharma. Merck was the ones that came up with the winning bid. So we sold OncoImmune for about$425 million, using$50 million to spin out the rest of that company's pipeline into a different company that I put together.

8:00And through that process of dealing with large pharma and their diligence practice, I knew enough right there that I will probably never, ever work for a large pharma company. Our side would be like three or four people plus maybe four or five outside consultants. There would be dozens and dozens of folks on the other end of the phone. at Merck is just, and everything, everything's a process in pharma, everything. And they're amazing at developing drugs and getting things to market, just not the environment for me. I just don't think, I think I would suffocate there. Is there a parallel there between that sort of organizational bureaucracy at a top pharma firm and going back to that hospital you were telling me about with that administrator who has away?

8:44I hear some parallels. Boy, that's an interesting – I had never thought of it that way, Dylan. I had never thought of it that way. Maybe you just uncovered something about my personality that wasn't even clear to me. Yeah, maybe large institutional – I worked for smaller banks most of my career. I worked for a couple of big banks. HSBC was one. Mizuho was another one. Those were big, large, global institutions. I didn't stick around. Those places were very, very long either. So, yeah, maybe it's got something to do. I like a smaller kind of move quicker, people wearing more hats, more diverse kind of day-to-day brines.

9:26Yeah, than a pretty more routine existence inside pharma or a larger institution. So maybe that's really where, yeah, maybe I found my home. You came on to Game Therapeutics 2024. You came in as CFO. Now you're president and CEO. What drew you to this company? So there are a few things. First of all, after having spent 15 years as a senior publishing analyst on Wall Street, you develop relationships and rapport with management teams that you cover because sometimes you work closely with them on understanding topics that you can then convey to investors and things like that. One such management team of a company that I covered when I was an analyst, Gentium, their CEO was a man named Khaled Islam, who was successful in taking Gentium really through a very rigorous FDA process, getting a very important medication for childhood oncology complications to market, and sold that company for a billion dollars.

10:30And we, you know, I sort of fought for the company in the in the capital markets world for a while. And so we got close based on that. Well, that was about 15 years ago or so, I think. No, maybe a little less than that. But, you know, and we kept in touch, Collett and I. And then he became chairman of a couple other companies. And along the way, we kept in touch from time to time. But he knew I had a background in neurodegenerative disease or cardiovascular disease. So, you know, I knew my way around the brain and knew the science pretty well. And so I guess in early 2024, when his CFO left to go do something off in Europe, he called me up and asked me if I would take a look at Gain Therapeutics.

11:16And right away, neurodegenerative disease is something that's been imprinted on me for a long, long time. So it's somewhere where I think I feel like I have a good basis of understanding so I can help from that perspective with strategy and things like that. And, you know, I like the company. I like the idea that GAIN is pursuing a first disease-modifying therapy for Parkinson's. So we're moving away from treating just the symptoms with dopamine and some of the other supportive care medications that are prescribed to support the symptoms of Parkinson's, but not the actual biology. We need to treat the biology of Parkinson's.

11:56So that's what GAIN's mission is with GT02287, or the purpose of GT02287, is to get to the biology and correct that. So that's really intriguing because it's doing something that would be paradigm shifting in Parkinson's disease. or an area of Parkinson's disease that has been willfully underserved as something that is disease-modifying that can actually stop the progression. So if that's a mission then, is that really what differentiates gain from these other companies? You're looking at the cause. You're not going to treat a symptom. You're not going to relieve a symptom. You're actually trying to reverse or change the trajectory of a disease?

12:32Yeah, well, it's a couple of things, too. It's a little bit complicated. It's not complicated, but it's a bit more granular. So GAIN's main mission is to develop small molecules, so things that are less invasive than injectable-type drugs, biologic drugs, large protein-type drugs, large biological molecules. So we're working to try and use small molecules to really, yeah, definitely get to disease biology in patients that are suffering from serious on-mett needs. It's not just neurological diseases. There's other neurodegenerative diseases where we think our approach may be useful, and we can talk about those as well, where there are commonalities in the approach that we're using in Parkinson's that work across other neurodegenerative diseases.

13:17There's also potentially, if we talk long enough, we can talk about the fact that we have potential oncology applications in our pipeline as well, because some of these targets also could be used in oncology or some of the things that our drug development platform Magellan is capable of doing is identifying druggable targets that are in oncology. So the small molecules that we want that we develop can span across indications. We're focused right now on neurodegenerative disease because we think we have a very, very good targeting matchup with a particular enzyme in Parkinson's. It's responsible for a lot of disease pathology.

13:56So we think that we're targeting that particular enzyme real well with GT02287. So that's our focus now. We mean to broaden that out as we develop GT02287 and advance that along. We think we have other promising things in the pipeline. It's been a little while since we had a deep dive into Parkinson's on the podcast. about 40 episodes ago now. Maybe we should just start by refreshing a little bit for people who are working in different fields. Tell me, how would you describe Parkinson's disease? What do we know about it? Who does it affect? Yeah, yeah, yeah. So Parkinson's disease is the second most common neurodegenerative disease in the United States.

14:34There's over a million patients now with Parkinson's disease. It sits second to Alzheimer's in terms of disease prevalence. So it is a significant issue in the United States as well as globally. Parkinson's is a nefarious disease. It sets in early and you live with it for decades and you live with a progressive sense of motor sluggishness. So patients describe walking in a pool of water or trying to walk through an ocean. It's just a constant struggle, a constant fight to keep your motor integrity. This is something and it gets worse and worse and worse over time. And we're also beginning to learn there are different phenotypes of Parkinson's.

15:21So there are Parkinson's patients that deal more with motor issues. There are Parkinson's patients that deal with more cognitive issues. There are other systems that are impacted dramatically by Parkinson's that create kinds of phenotypes of Parkinson's patients. So some in the field argue that it's not Parkinson's disease, but Parkinson's diseases, which is now, you know, first of all, we've had a hard enough time just cracking Parkinson's alone now to learn that there are ways we might have to individual. But that's how you get to the under, that's how you get to disease. That's how you really start to understand it and start to treat it for all because you can learn across these different phenotypes.

16:03So in our particular case, there's a genetic mutation in some Parkinson's patients. It's their GBA1 gene. This particular GBA1 gene encodes the enzyme target of GT02287. So GBA1 codes for an enzyme called glucocerebrosidase, which, not to get too technical, but is responsible for cleaning up a lot of toxic waste in the cell, usually through the lysosome. But it also performs some other stabilizing functions in the cell related to energy production in the mitochondria and obviously stress issues in the endoplasmic reticulum and other cellular compartment where the protein is trans. So it's got a pretty complicated traffic pattern through the cell it needs to get to.

16:50What GT02287 does is binds to the enzyme. Even if it's misformed from the genetic mutation, it stabilizes and protects that enzyme and then chaperones it through that traffic pattern. And there we think we're able to drive neuroprotection by doing that. So there's already treatments, or I should say there's already therapies out there for Parkinson's. Why do we still need better options? What's the limitation with the therapies that we have right now? yeah well the limitations of therapies are that you're gradually going to have to increase the dose um and uh you're gradually and they're gradually those drugs are gradually going to wear off you can only you know what you're basically doing is uh bombarding with dopamine for example you're you're just pushing more dopamine into the brain while the receptors that can take that dopamine in that in the cells are slowly dying off anyway so at some point no matter how much dopamine you put into that system, if the cell can't absorb it anymore, if it can't get to where it needs to go because of the neurodegenerative pathology underneath it, then the dopamine is going to start losing efficacy.

17:56And that is indeed what happens as the disease progresses slowly over time. We're trying to get, so what GT02287 promises to offer, hopefully if we're successful, is a new backbone of treating Parkinson's disease. So those patients that have symptoms, we're able to stop it there. We can't bring back dead neurons. So, you know, patients who have experienced a significant symptom or significant disease progression in Parkinson's, there might not be much we can do to repair what has gone. Now, we can talk separately about things like, you know, brain plasticity. And if we can keep patients, you know, stabilized in their disease, can we then at least get them to a point where they can see a therapist and work on some muscle coordination, work on new ways to build new neural networks over time?

18:48But that is a long, arduous process. The key now is let's demonstrate we can do something to impact the disease progression in patients that have symptoms so we can understand how the drug is working. And hopefully we can gradually just move it earlier in the treatment paradigm for all Parkinson's patients so that we get to them before the symptoms are severe or even really noticeable. And so what we want to do with GT02287 and why it's different than the other therapies is we'd like this to be now the new backbone. When you feel like when Parkinson's seems to be setting in, GT02287 is your first drug.

19:21And you basically are hoping to either slow or stop the disease progression. And maybe you add dopamine in much, much less and much, much less over time. So your overall dopamine requirement is lower. Or maybe If we're lucky, we just don't know enough yet, and we need to do more studies with GT02287, maybe we can just arrest the symptoms there. You're stable on whatever dopamine you're using, and for patients that are early, they never need it to begin with. That would be the ideal. That would be the home run, so to speak, in getting GT02287 to patients bedside. So maybe there are more studies to do, but you've already done into phase one with GT02287.

20:03um you've got some early results early readouts there anything about the potential just to modify the course of parkinson's yeah we've seen some really exciting um uh data from our phase 1b study um the most important of which is some biomarker evidence that we are actually um you know targeting uh the enzyme glucocerebrosidase g case for short so you'll hear me use those terms interchangeably as we go along. So G-Case, along the G-Case pathway, it's one thing to show that you can activate the enzyme or increase its activity. It's another thing to see to some biological end of that cascade and is your hypothesis in terms of disease modification happening.

20:52So what we're seeing, in addition to, you know, we had early evidence that we were activating the enzyme. And now what we're seeing actual Parkinson's patients in phase 1b, that's a healthy volunteer study. Now in actual Parkinson's patients activating their GKs, or at least protecting their GKs, or stabilizing their GKs with GT02287, that is leading to other biomarker evidence of efficacy. So we're seeing toxic lipid substrates in the cerebral spinal fluid that were reduced in the presence of GT02287. And the early clinical impact of that appears to be in its early days and we have again we have to prove these results in additional larger trials but the early results of this is that it is promoting a more robust response in some patients that have high levels of this toxic lipid substrate in their csf so patients who came into the study with high levels of a lipid substrate called glucosyl sphingazine it's another malone salad uh glu sting for short uh uh but uh patients who had a high level of that they apparent their their clinical measures their clinical outward appearance seem to improve uh to a greater extent than those that had lower levels and we think all patients will will benefit but we may have differential response in some of these so we're going to continue to watch these markers as we as we uh get into larger larger clinical trials with gt02287 so we find biomarker evidence of this and it's this toxic lipid substrate and some other cellular signals that are changing, we think for the better in the presence of GT02287.

22:28So all of this tells us not only are we able to actually get to the target G case, but the biology subsequent to that is working in our favor, hopefully, and we're seeing that in some clinical presentation of these patients. One of the other things I found really interesting about your approach is where this asset actually came from. It came from the Magellan platform, and that enabled the discovery of this sort of molecule that was pretty difficult or even impossible to develop before. What can you tell me about this Magellan platform? Yeah, so that now goes back to Khaled Islam, our scientific founder and chairman of the company.

23:04So I told you earlier that after Gentium, he went off to join lots of boards and help smaller companies achieve the success he had with Gentium and some other companies like Immunomedics. So one such company is a company based in Spain called Menorix. Menorix had, you know, about 10 years ago when GAIN was started, had some late stage assets that it was primarily focused on, some early stage pipeline candidates that seemed to be, for lack of a better word, you know, on the slow shelf. So Dr. Islam came up with The idea of let's take these molecules, which were found on a discovery platform at the time that was called CTEX.

23:47So Magellan's initial iteration was this platform called CTEX. Dr. Islam brought in CTEX plus this portfolio of molecules, one of which was GT02287, into a company called the Gain Therapeutics. And the interesting thing about gain therapeutics is the mission of the company was to use CTEX to identify unique binding pockets on proteins that were previously thought to be undruggable and come up with molecules that could fit into those binding pockets to get a gain of function in those enzymes. So the idea behind it is we don't necessarily want to – we can develop molecules that are inhibitory because sometimes you need to shut switches off in the body.

24:30But the primary focus of GAIN was to take underperforming enzymes and proteins and increase their function. So that's what we consider the approaches for GT022x with Gcase. We're improving its function, its gaining function, not losing it in the cell. So GAIN Therapeutics was formed with CTEX and this first portfolio of molecules. And slowly over time, we moved GT02287 into the clinic. We've also improved the CTEX platform to include this AI, which includes then a proprietary set of physics calculations, just to give it a simple term. that's our sort of secret sauce into Magellan and it can move through these algorithms quite quickly from calculations that would normally take to find these because you find what Magellan seeks to do is understand the kinetics the binding and unbinding kinetics of molecules into proteins so that's a lot of calculations that need to be done can take a very very good computer 10 to 15 minutes we're trying to use supercomputer and bring that down to you know milliseconds if we can um and And it's constantly working through these calculations.

25:45So that became Magellan. And as that was being improved upon, GT02287 made its march from pre-IND designation to now having an IND in front of the FDA and also a phase 1D study ongoing in Australia. So we're really quite proud of having taken an asset that, you know, probably, you know, minorists might just might not have been able to get around to it at some point. So we brought that in to advance the development and we've achieved just that. So with this AI and with this really physics-based modeling, how does that change the way you approach drug discovery now? You talk about this acceleration.

26:26Is it just going faster or is it doing something else too? It's going faster but it's also doing other things as well. So up till now, most compound screening, you know, so when companies are looking for a way to target a disease, they look at, you know, what's in the public domain in terms of compounds that are out there. And then they screen those compounds against their protein target or enzyme target or biological target to see what sticks and what doesn't and what's working and what doesn't work. So up to this point, you screen these libraries of compounds. Now we're getting to the point where we can maybe construct molecules never before known to the public domain.

27:06So these are things that are completely novel. And that's what we're trying to do with our AI platform, too, is to go beyond what's in the public domain. Maybe create new libraries of molecules never before thought of because the processing power just wasn't there. The limitation here is no matter what you discover on a molecular basis, you've got to get it through the clinic. And there, AI can't help us yet too much. I think it will eventually and probably in a big way. But for now, you still have to do slow clinical trials. And so you get this logjam of, you know, you can discover compounds all day long.

27:41You've got to prosecute them through the clinic. So we've been sort of saying that for a very long time. We're not new to AI, even though a lot of biotech has become familiar with over the last few years. We understood its limitations early on, mainly. It can't help you in the clinic. So we've never really promoted it too much, other than to say it's a very, very capable drug discovery platform. It's led us to where we are. We believe it's going to be a lot more, but we've got to get GT02287 through the clinic in order to validate it. So tell me about these next steps for GTE 02287. You know, you're in Phase 1B in Australia, you said.

28:20Is Phase 2 coming along? What are the next steps? So what we did in Australia was a sort of – so our Phase 1A study was a standard Parkinson's first in human being safety and tolerability assessment. We also saw the target engagement there with G case and all, But the primary purpose of that was obviously safety and tolerability. That's the same purpose in a phase 1b too. So Parkinson's patients are vastly different than healthy volunteers. They're a much more fragile population in a lot of respects. They are taking other medications. They typically have other comorbidities. So it's another safety study that you're doing primarily to make sure that your medication, GT02287, can safely and tolerably fit into their life.

29:07So, so, so we're, but, you know, given the fact that we also need to try to understand the activity of the drug, we are looking at some signs and signals of efficacy. These are things that are not going to be statistically significant in most respects, but you look for directional signaling, you know, is this, does the bio, is the biology responding to us or is it not? And I think that's what we're seeing now is that the biology is responding to us. So in the phase 1B, we did a 90-day trial to assess safety, tolerability, and early biomarker evidence of activity. And that is where we saw the lipid movement in the CSF that I had mentioned earlier.

29:43It was in that 90-day sampling. So we were really, really excited about that. The clinical presentation and the clinical benefit that we saw is something that we take with a grain of salt. We're very gratified to see it. But we are all skeptical scientists. We need to see more of it in larger trials, but we are very, very excited about the early signals here. And also the fact that we seem to be seeing a different response among these patients. So that first 90-day study was then expanded due to what we thought was a very, very good patient experience. we offer to keep patients on drug for an additional nine months so they get a full year of therapy and an open label extension we can understand more about the drug see more of the clinical impact that the drug is having and and potentially some more biomarker evidence at the end of the year when patients come off of the study so this was a study that was meant to establish safety tolerability early signals of efficacy that we expanded so we had 21 patients in the study to start, 19 of them finished.

30:52And then from those 19, 16 elected to stay on the open label extension. And we've kept all 16 patients so far, which we're really gratified. It's not a hard medication to take, but it's also not you just open up a bottle and take an oral pill, right? So you have to do it. It comes in a powder form. It's in a packet like a Swiss Miss hot chocolate packet. So you open that up and you can sprinkle, you mix it and then you sprinkle it and you add water and drink it. So it's like a suspension. So it's not complicated. But if it's not working, I don't know that we'd get really good compliance that we're getting in the patients who are continuing to take this every day.

31:30So we are going to complete the phase 1B study in Australia. In the meantime, we have an IND before the FDA that we're expecting to get cleared this quarter. So over the next couple of weeks, we expect our IND to be opened by the FDA. And then our phase two study will begin in earnest next quarter, in the third quarter, and we'll also include the U.S. now, as well as potentially some European centers as well. So we can enroll this study as quickly as possible. So we'll be in Australia, potentially a couple of centers in Europe, and then definitely in the United States for our phase two study. So phase two, that's fantastic.

32:11But are you looking to partner there? Are you looking to bring in someone, a bit of clinical experience, definitely commercial experience? Yeah, so right now, so my view on the commercial, we're a bit away from commercial strategy at this point, particularly because if we're successful, commercial strategy pretty much takes care of itself. This is a drug that will not sit on shelves. So the commercial strategy, we think, will be cleared by our clinical and regulatory path. What we're going to do for phase two, we'll either finance the phase two study on our own. We are talking to partners who are the other aspect of our data is no one's done it before to don't.

32:57So that makes things a little bit more. It makes things a little bit more deliberate in terms of diligence process and so forth, because there's not a lot of data to compare our our results to in the public domain. So a lot of partners are taking time understanding the biomarker evidence that we have and the other data. And we have been engaged with them for years in some cases and are looking forward to learning more and are doing their diligence in real time as you and I speak. So we continue to engage with partners. We'll see over the next several months what that leads to. We can start the phase two study and export no problem on our own.

33:40We may choose to continue to do that on our own and finance it ourselves, partner with one of the groups that we're talking to currently, or some combination of the two, so we can also advance our early stage model tools as well. Let's look a little bit bigger picture here. You've got this AI-driven platform, Magellan. It's fantastic. It really speeds things up. What do you see as the big opportunities for these sorts of platforms in biotech for the next five or ten years? Is it just about speeding things up or is it discovery as well? Yeah, there is a discovery aspect of this. We could potentially discover newer, better, more tolerable, more efficacious molecules going beyond what's in the public domain now.

34:24But again, I think the big limitation we're all going to live with is until AI has a larger application in the clinical development and the clinical regulatory process of drug development, again, you're going to just have this logjam of compounds waiting to get access to patients or waiting to get into a clinical study. until AI can mimic clinical studies quite reproducibly and quite reliably. I don't see it impacting the clinical development cycle. But, you know, bench to clinic will go much faster. That's kind of the clinic to patient stays the bottleneck. You've seen biotech from a few different positions over the years, whether you're there in the operating room, you're on Wall Street, You're in biotechs now as a CEO.

35:18What sort of advice do you give other leaders who are working in these neurological disorders where there's a high unmet need, but not really anything addressing the root cause of the problem? Yeah, there's a few things. You know, we I will tell you that neurodegenerative diseases, particularly in Parkinson's space, I think there is already I have seen other disease areas and contentious areas of disease development where multiple sponsors, multiple companies, even ones that are of similar size and look and competing investors even working on similar molecules after the same target. and it can get really vitriolic.

35:58In Parkinson's, I think the need of the patients has overwhelmed the field with a sense of duty. And I think we share a bit more. We are a bit more collaborative and that's really what you need to be. I mean, a lot of times it's best for all parties, put the swords away and work together in some respects to help the field. it's an easy thing to say and it's a hard thing to put into practice that's probably number one we've got to figure out a way to work better together you know and for three decades since I've been around biotech I've heard about you know you got to publish your failed results you got to publish your failed results you got to publish your failed results I still don't think we do that enough because there's a lot to learn from failed studies I heard one Parkinson's field expert in a big conference once get up and say there's no such thing as a failed study that that just doesn't exist.

36:55And there's some wisdom there. But yeah, so so that's one of the things, you know, persistence and planning, you know, making sure that you are clear on your development path and that you understand what the regulatory requirements are and how they may move. Like, I don't know that we'll be able with all of the technology that's coming on in Parkinson's and in neurodegenerative disease in general. I'm not sure. The gold standard right now for approval is the MDS-UPDRS clinical scale. That's the one thing that I've been referring to when I say the clinical presentation. It's how these patients are doing on that particular disease severity scale.

37:36It's what the FDA requires for an approval of a drug. You have to show meaningful improvement in that scale and a couple of number of parameters in order for the FDA to approve you. I think this is going to become a less and less reliable avenue for approval with technology that may better define disease state and progression over time. I think that's probably one thing that the field needs to start to adapt to is that we need to start integrating some of these new technologies into our studies so we can also help inform the field how these things are performing. So we're doing that as well in our phase two study.

38:19So we're adopting some outside technology for secondary endpoints to measure things that we don't know are being picked up robustly enough by that MDS-UPDRS score but are still meaningful to patients. So these are ways that I think the field needs to work to be creative and to be thought-provoking and creative in the way that we're addressing these patients to come up with better tools to evaluate them and treat them. There's a lot to do in neurodegenerative disease. We are woefully behind other disease indications in the last 30 years. I mean, we have not put up points on the scoreboard, meaningful points on the scoreboard in a long, long while.

38:55Gene, it sounds like there's really exciting stuff going on again. Where can people follow along? Where can they learn more about the work you're doing? Yeah, I mean, so, you know, we're a publicly traded company. So we have to make noise. We have to announce things. So, you know, the website's always tracking down the conferences. And right now what we're trying to to do mostly is build awareness of Parkinson's. You know, in the prior administration, before this new one took over, there was a bipartisan bill passed. I mean, you can't get a bipartisan bill passed for a free beer these days, let alone a Parkinson's initiative, where both sides of the House and Senate kind of agree that this is a national problem that could benefit from the government putting the wind at the backs of the field.

39:47And it was a bill that everybody agrees with, but no one will fund. So I'm trying to do some saber-rattling around this bill because I think it's an easy win for anyone who will take it up and say, okay, the government wants to start supporting research, start trying to move the ball forward. I mean, we cracked COVID that way. There was enormous effort on the part of the government to move things forward. And it worked once, and they don't want to do it anymore. So let's get behind Parkinson's, get behind this bill, put some financing behind it so we can do things faster. And if we fail, we fail, we move aside and let the next party through.

40:25But we think we're on to something. We think it's just, you know, financing is always hard to get. Regulatory requirements are expensive. These types of things work together to keep companies really struggling. To the extent that we can remove some of these obstacles, we may be able to make a dent quicker. so what i want to do is get everybody focused on government and trying to move and get things finest which is probably like everybody's like what is it where has this guy been in the last 10 years um but but that's that's i think a responsible way a uh a non-argumentative way uh to get everybody to focus on what we're real priorities uh and that's you know you know fixing something, you know, a physical condition that has languished for decades and decades, and it impacts every single one of us, some way, shape, or form.

41:15I know no one that's listening to this podcast is not impacted one or two degrees of separation from Parkinson's. I know that's a talk. Gene, let's hope there's some movement there. Thanks for joining us today on Beyond Biotech. Thank you, Dylan. It was a pleasure. that's it for this episode don't forget to check out all the latest news and analysis at labiotech.eu i hope wherever you are in the world you have a great week ahead thanks for listening and i hope you'll join us again next time for another beyond biotech

42:00Amen.