The best biotech conversations you missed this summer

0:05Per Lundin: Hello, and welcome to Beyond Biotech, the weekly podcast from La Biotech. I'm Dylan Kassane, and this is episode 215 for the podcast. Summer is a busy time for everyone, guests and listeners alike, so today we're taking stock. This is our summer recap, an episode where we pull together the best moments from conversations you might have missed over the last few months. We'll hear from Randy Thiel of Arvanus and Per Lunden of Evox on two very different ways of getting drugs to the brain, and Lauren Levy of Nanobiotics on outsmarting the liver altogether. We'll meet the founders behind these companies, including Andy Parker of Step Pharma and Gene Mack of Game Therapeutics, and the unlikely paths that got them there.

0:51Per Lundin: We'll dig into the science of nonsense mutations with Nerissa Crea of Altena, circular RNA with Lou Gow of Therona, and a cancer target hiding in human genetics. And we'll close with what those leaders think success actually looks like years from today. So sit back and let's revisit some of our favorite moments from the summer. But first, a word from our friends at Inside Biotech.

1:22Gene Mack: Hi everyone, my name is Karish Manjigani and I'm the co-host of Inside Biotech, the official podcast of Biotech Connection Los Angeles or BCLA. For those who may not know, BCLA is a nonprofit organization dedicated to inspiring, educating, and connecting emerging scientists, students, and entrepreneurs to help grow and diversify the biotech ecosystem in Los Angeles. On Inside Biotech, we invite you to get a behind-the-scenes look at one of the fastest growing biotech hubs in the country. Each month, we sit down with scientists, founders, investors, and industry leaders to talk about the cutting-edge science inside their companies and the personal journeys that brought them there.

2:01Gene Mack: From breakthrough therapeutics and AI in healthcare to career transitions beyond academia, we explore how science, business, and storytelling intersect to shape the future of biotech and SoCal. If you're a student exploring careers in STEM, a young professional navigating the industry, or simply curious about the people driving innovation, this podcast is for you. Search Inside Biotech wherever you get your podcasts and give us a listen. We'd love to have you join us.

2:32Per Lundin: A drug is only as good as its ability to actually reach the target. It's obvious, but it's also the single hardest unsolved problem in biotech right now, especially when the target is the brain. Over the next few minutes, three very different companies explain three very different answers to that same problem. First, Perlunden from Evox. Yes, so for our Huntington's program, for instance, we are using something called convection-enhanced delivery. So essentially, we go directly into the brain using a device. So we're essentially, for Huntington's, we utilize our exosome delivery system as a way to ensure that we maximize the spread of our gene editor in the context of the striatum.

3:22Per Lundin: So this is done through a neurosurgical procedure where you go in with a device and then deliver the drug product into the striatum directly. And this really gives you maximum exposure to the key brain region, which is important in Huntington's. But it also is really suitable for a modality like a gene editor or for a gene therapy because we are doing essentially a single dose. This is done once. And so, you know, if you think about that, you know, it's of course an invasive approach to do neurosurgical procedures and you prefer to take a pill or do an IV infusion. But if you're only going to do it once and you know that you want to have maximal efficacy, well, then going directly into the brain is a very, very helpful way of thinking about central nervous system diseases.

4:08Per Lundin: Peir's approach is to go around the blood-brain barrier altogether with a neurosurgical procedure. Randy Thiel, CEO of Avanus, is trying to get through it using nothing but the chemistry of the drug itself.

4:22Andy Parker: We get asked this question a lot, as the blood-brain barrier, as you said, has been a challenge to get therapies into the brain. And so we always get asked if we're using some sort of active transporter or some other mechanism of doing it. The answer is no. The answer is medicinal chemistry. The answer is that, you know, just as our scientists were able to, back in the 2016 timeframe, able to figure out how to get a protactegrader, which, while it is a small molecule drug, they're typically a little bit on the larger side, which makes it more difficult to do things like get it into the brain or even cross the gut and be orally by a bill by, you know, so that you can take tablets by mouth.

5:05Andy Parker: very similar to how our scientists figured out a way to cross the gut they figured out a way to cross the blood-brain barrier too so i can't go into the details of exactly sort of the rules of of medicinal chemistry design that we use but it's one that we've been able to solve and we have shown pre-clinically and clinically now for arv 102 that the drug gets into the brain gets into the CNS, which is important because in the diseases you mentioned, which are of course diseases of neurodegeneration, we needed to degrade the target in the brain in the CNS. So that's a program that is in phase one now and just had some great data read out a few months ago, and then we'll be moving into later trials before too long.

5:54Per Lundin: Both of these are about getting a drug to the brain specifically. Laurent Levy, CEO of Nanobiotics, is tackling a related but broader problem. How do you stop the liver from clearing out a therapy before it ever reaches its target, anywhere in the body?

6:10Randy Teel: We still try to look at an issue that our industry has, but from a different angle. And here we've been looking at some of those very innovative objects and therapies that people work on, like cell therapies, oncolytic virus, some RNA-based system, in vivo CAR T, all those things. When you think about it, all the subjects, they share an issue. They share a limitation, which is the following. When you inject the subject IV, because they are different from what the bodies used to see, they are eliminated, sometimes close to 100%, sometimes less, by the reticuloendothelial system. So, for example, the liver is playing a key role to eliminate the subject to the point that when you inject sometimes one of the subjects out of one million objects injected, you will find one in the target.

7:08Randy Teel: So you have a big loss that either bring lack of efficacy or sometimes increase like the liver toxicity, that kind of things. And it's not one product. That's literally hundreds of products that are under development, if not thousands. So the question is, shall we do like the industry is doing, which is trying to tweak the subject to make them escape the lever while they also try to optimize the pharmacokinetic, also the delivery, also the transfection in some cases. So in one object, they try to do everything, and then you make more and more compromise. So instead of going that direction, what we decided is to create a second object that we call a nanoprimer.

7:51Randy Teel: this nanoprimer is made to be injected before the therapeutic agent and the nanoprimer being injected iv is going into the liver keep the liver busy for a certain amount of time and when you inject your therapeutic object is going through being less captured by the liver therefore you can increase circulating quantity of product and efficacy but also reducing toxicity when it comes to liver toxicity.

8:19Per Lundin: Three totally different engineering problems, three totally different solutions. But none of this happens without somebody deciding to bet their career on it. That's next as we take a look at some founder journeys.

8:38Per Lundin: Not everybody plans to become a biotech CEO. Take Gene Mack of Gain Therapeutics.

8:46Laurent Lévy: yeah so okay the origin story um i guess that begins um kind of with some curiosity around medicine i old family members uh a fair amount of family members who are physicians it seemed to be one of the more respected um avenues to take if you want to respect uh you know in the mac household um so so i i slowly gravitated over uh medicine um strongly influenced probably by My older brother is 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.

9:25Laurent Lévy: And prior to medical school, I did a research fellowship hybrid kind of thing at Columbia University in their Department of Interventional Neuroradiology. It was a big mouth style. These are basically guys who did video and contrast imaging of the brain and the cerebral vasculature. And the department that I worked for mainly tried to diagnose these 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. So 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.

10:09Laurent Lévy: 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 time 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 their own publication purposes. So a very, very big diversity of research interest in an operating room in neurodegenerative disease and cerebrovascular disease. So it was exposed to a lot very early. What I learned is medicine's fun, but very difficult.

10:43Laurent Lévy: And beyond dealing with, you know, your day-to-day patient interaction and just treating the patient and 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 a patient. I just, you know, in your mid-40s and 50s after all the investment, I just, so 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.

11:19Laurent Lévy: 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 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.

11:45Per Lundin: Gene came at Biotech from the capital markets. Laurent Levy of Nanobiotics came at it from an altogether different direction, a PhD in physics with no biology training whatsoever.

11:58Randy Teel: Well, maybe we can start with my training. I've been trained as a physicist mainly, I did some biology too, but my main stream learning was physics. And I did my PhD in nanophysics, trying to understand what's happening with the laws of physics when you start reducing the size of the material. When you come to nanometers, laws of physics may be tweaked, may change. And that was the basis of my thesis. And later on, I did a postdoc. And in between, I was wondering what I should do with my life. Should I go to semiconductor industry? Should I do something else? But I always wanted to have an impact for people.

12:38Randy Teel: So what better field than trying to improve health of people? That's why I'm starting to think about how can we apply all this new emerging field of nanophysics into doing something to cure people from different disease. And I was there at the beginning of the whole story.

12:56Per Lundin: You know, the tagline on the website there is building new therapies atom by atom. Where did this idea come from? What was the original insight? Was it back in that doctoral work?

13:08Randy Teel: Well, I mean, technically, that's what we do. You know, we do bottom-up approach, meaning we have to start with atoms that we assemble, not one-to-one exactly, but few-to-few, in order to build those nanoparticles to have very specific physical properties. If you start from a big material, try to reduce the size, you will obtain something very different. So the ability to build complex objects, complex nanomaterial, has to come from building almost atom by atom. So that's technically what we do.

13:43Per Lundin: And for Peer Lunden at Evox, they came from somewhere you really wouldn't expect, the law. Well, yeah, it's a good question, actually, Dylan. And to some extent with this company, I have stayed for 10 years, but I do like new things, right? I think it's ultimately one thing that I think brings people to biotech more broadly. And I think that's, you know, hopefully making a difference for patients, right? And so, you know, I've been mostly engaged in companies working on advanced modalities, but it tends to be about unmet medical need, you know, patients going through a really difficult time with a given disease and then trying to find a solution to that.

14:21Per Lundin: And I think that brings a lot of people to biotech. But, you know, the other thing that I think brings people to biotech is that the science is exciting, right? So, you know, we work on gene editing. I worked on cell therapy, gene therapy, RNA therapeutics. You know, these are exciting things to work with. And, you know, you know that you're working on important things. And at the same time, it's, you know, intellectually stimulating. So I think, I guess that's the thing that brings me back. But I've certainly tried a corporate job as well. But I find biotech to be a bit more dynamic and exciting in many respects.

14:52Per Lundin: A trader, a physicist, a lawyer. What they share isn't a background. It's a decision to go build something instead of just study or represent it. and building means constantly defending a very specific scientific bet. Let's take a look at the science.

15:13Per Lundin: Here's where the science gets specific. Three founders, three completely novel mechanisms and in every case a story about why nobody had done it this way before. Here's Andy Parker of Step Pharma.

15:28Gene Mack: Yes, so we target a pathway called the primidine synthesis pathway. So this is a pathway that's actually producing CTP, and CTP is an integral component of DNA and RNA. So essentially what we're trying to do is to block DNA synthesis in cells. And if you block DNA synthesis in cancer cells, for instance, then what happens is that they stop dividing. And if you can hold them there for long enough, then what happens is that those cells go into apoptosis, into cell death and actually then die. So that's the mechanism that's actually quite well understood in the cancer setting. But what's different here is that most approaches that try to block nucleotide synthesis don't do that in a tumor specific way.

16:19And so consequently, if you block nucleotide synthesis throughout the body, you also block cell division in those cell types that are actually important for normal life.

16:29Gene Mack: And what you usually see in a broad nucleotide synthesis inhibitor is gastrointestinal tox, because you've blocked replenishment of the gut wall, you end up with mucositis, with diarrhea, and that prevents and has prevented development of drugs that target this particular pathway. The reason that CTPS1 is interesting and different partly comes from the human genetic story. So Alan Fisher, one of the founding scientists, he identified a found a population of kids back in 2014. They were in the UK who were unable to mount a response to a viral infection. And what they showed was that that inability to mount that response was due to a mutation in the gene that codes for CTP synthase 1.

17:18Gene Mack: So essentially a null, so almost a complete loss of function, meant that your lymphocytes couldn't proliferate. And then what was most important was that CTPS1 also has an ortholidus enzyme, CTPS2. and every other tissue type in your body in the absence of CTPS1 can use CTPS2 to make whatever CTP they need to carry out normal function. So that was a sort of eureka moment that if we could truly target CTPS1 selectively we could block aberrant lymphocyte proliferation in for instance the lymphoma setting and that is unique in the pathway that we're targeting. So that pathway We have sort of six or seven biochemical steps.

18:01Gene Mack: And every step in that pathway, there's one enzyme that can catalyze the substrate to product conversion, except that final step where we find ourselves with CTPS1 and CTPS2. So really what we're doing is exploiting the situation where everything is dependent upon CTPS1. So in lymphoma, lymphocytes can only proliferate if they have CTPS1. It doesn't matter that they have a low level of CTPS2. And then we've gone on to find other situations where CTPS1 is an absolute dependency in solid tumours and also then in essential thrombocytemia. So it's really finding that exquisite point in time where you've got that dependency that means you can block nucleotide synthesis, have the desired effect, whilst sparing all the other tissue types.

18:51Per Lundin: Nerissa Crea, Chief Medical Officer at Alterna, is working from the opposite direction. Not one gene, but a mutation type shared across dozens of unrelated genetic diseases.

19:03Gene Mack: Certainly. So, as we talked about earlier, there are many, many genetic mutations that can cause diseases. And there are multiple categories. One would be nonsense mutations, which we are currently focused on. Others like missense mutations. And these basically just mean what does it do to that process we were just discussing from mRNA to protein. In the situation of nonsense mutations, the nonsense mutation actually leads to a stop signal. So that translates into something we would call a stop codon. So instead of it being the code for an amino acid like it's supposed to be, the code actually is telling the body that it should stop making the protein.

19:59Gene Mack: And in nature, we have lots of those that exist normally because we do need proteins to stop being manufactured. But in the situation of a genetic mutation causing a disease, that stop signal comes too early in the protein manufacturing. So these nonsense mutations essentially are telling the body to stop making a protein too early. And then you don't have the functioning protein that you need, ultimately leading to disease. So in the situation of our tRNAs, specifically AP003, it reads through that, recognizes that, oh, this is not supposed to be a stop signal. This is actually supposed to be the code for a specific amino acid.

20:51Goes out, finds that amino acid, brings it back, places it into the protein chain, and then that protein is growing appropriately as a functional molecule.

21:04Per Lundin: And Lu Gao, CEO of Therona, is working with a molecule most listeners have heard of in its linear form, mRNA, but bent into a circle. Sure.

21:17Gene Mack: Yeah, the premuse intra-exome method is quite famous. Actually, the concept started in 1990s in publication that we wrote earlier before even ONA took their initiative in enhancing the efficiency. So what ONA did was they had a special design in the PIE splicing fragments. Specifically, they include additional homology arm and spacer region to facilitate the splice sites recognize each other so that splicing could happen effectively in vitro. So basically, there are a number of companies or labs are using different arrangements of the intron and axon fragments. And some of them add different type of sequence or structure in between them to enable the splicing.

22:31Gene Mack: So what we did is we have tried quite a number of different methodologies. And one of them is splint-free enzymatic ligation method that we have applied it in our clinical products. we have manufactured using the splint-free enzymatic method for different products. So the difference is that we split the iris, which is an internal ribosome antocyte that's responsive for protein translation initiation in vivo. So we split that and place them at two sides of the coding region of the RNA. So our linear mRNA after in vitro transcription could form a secondary structure so that the 3' and 5' will become naturally in the proximity so that we add a ligase that's very easy to ligate it together.

23:50Gene Mack: And the beauty of this method is that we do not need any splicing, and therefore we do not generate splicing byproducts that you need to purify them away in the process. And the reaction condition is also very mild, and we generate a scarless circularity, meaning that we do not need to introduce any additional sequence in the RNA other than the iris and the gene fragments.

24:20Per Lundin: Three genuinely novel mechanisms and in each case years of unglamorous platform building before there was ever a patient in a trial. Getting that far takes money and increasingly it takes good decisions about who you're willing to build with. Let's take a look at the business.

24:41Per Lundin: Great science doesn't fund itself. Let's take a look at the deals, the financing, and in one case, the geopolitics that shape whether a therapy ever reaches a patient at all. Here's Laurent Levy of Nanobiotics.

24:56Randy Teel: Well, I think again, if we look at the attention around the company for the past 18 months, I think people start to see the value of what we create. Obviously, some have seen that before because they are shareholders for quite a long time. And believer, if I think about Inverse or QIA, for example, that have been a long-term supporter of nanobiotics. But there's more and more biotech investors coming in, also some very long-term sovereign fund that we have seen joining the band. So it's time. When you do something disruptive, there are pros and cons, or at least advantage and disadvantage. The advantage is that you're alone.

25:38So you have time to bring something very established, but it takes more time.

25:46Randy Teel: It takes more time and it takes more time to convince people that this could be useful and valuable. But little by little, we're getting there.

25:55Per Lundin: What are you going to spend the money on? What do you do with it? is it enabling something a new trial or something that wasn't there before

26:03Randy Teel: yeah something that there was two um two purpose uh of that uh fundraising first of all is to accelerate the different platform and now we have visibility into 2029 and this without any milestone payment or revenues coming from jnj so we have time to build not being dependent on the money coming in from J &J, but more importantly is to accelerate what we are doing, like the development of the nanoprimer and some other projects that are cooking. Randy Thiel at Arvanus is managing a more complex version

26:43Per Lundin: of the same problem. Not one deal, but a whole portfolio of partnering decisions across multiple programs.

26:51Andy Parker: Yeah, and I think the word platform there is important, right? So I think Arvinas is probably one of the strongest examples of a platform company that you'll find from the ability to take a technology and rapidly implement it into multiple programs. But make no mistake, you know, as for a company of our stage, investors will look at us for the programs that we have in the pipeline. Program is wonderful, but I don't think anybody is going out right now and saying, investors, you should invest in us because we're the best at making antibodies or ASOs or some other modality. And so I don't expect anybody to look at our Venice and say, OK, they make great pro tech degraders.

27:33Andy Parker: I'm investing in that. People right now are going to invest in programs. So that's a really important view for a small biotech, a small pre-revenue biotech, where we still rely on investors to fund what we're doing. So that actually helps narrow the field, right? Because that means that what we're taking forward and what we're known for has to be something that investors can get excited about. In my history at Arvenis, I've led both business development and investor relations. You can talk about the same program with big pharma companies and investors, and one group gets more excited than the other.

28:10Andy Parker: This happens all the time. Like, I will tell you for sure that the big strategic partners typically have a much longer term horizon for what they're interested in hearing about than investors do. And that becomes important because it means that what we're taking forward has to be investable in a way that is not necessarily the case for something that we're going to partner with a big pharma company. And the other thing to think about is it'd be really nice to take everything to late phase two or phase three and then partner it. That gets pretty expensive pretty fast. So the other thing we try to do is identify what data do we need to generate to get ourselves excited and make decisions, to get investors excited, to help with financing and to get partners excited.

28:54Andy Parker: Because whenever a company announces a partnership, it's not like it just came up a month ago. Those conversations, I'm sure everybody would tell you, are the result of years of work. I'll give you an example. We kept many big pharma companies up to speed on our progress with our androgen receptor degraders for a lot of years before we ultimately partnered with Novartis in 2024. That didn't just happen. Those conversations had started before I joined the company in 2018. And so as we think about prioritizing what we do versus partners, all that comes into play as sort of what's the triangulation between what we can invest in, what a partner wants to invest in, what investors want to invest in, and that's the complicated math that we're doing.

29:41Per Lundin: And Lu Gao at Therona is navigating something none of our other guests have to think about, raising money and striking deals as a Chinese biotech against a backdrop of real geopolitical scrutiny.

29:54Gene Mack: Yeah, especially in this CAR-T field and in vivo CAR-T field, we did observe there are quite a few deals already. However, there hasn't been a deal with Chinese spell tech or pharmaceutical company so far. And we hope that we will become one of them or one of the first in this area. I guess I do see that there might be some difference in dealing with American biotech versus dealing with Chinese biotech. First of all, we could see there could be communication gaps and awareness gaps. I do observe that big global pharmaceutical companies are investing heavily in the last two years in China and put their resource in terms of partnering in the local force to be able to interact with Chinese biotechs.

31:04Gene Mack: And this is very important for them because they need to gain first-handed information and more thorough communications with Chinese biotech to understand each different project's problem counts. and when such similar deals happen in US, such interaction could be much simplified and hopefully that will change the trend in the next couple of years.

31:39Per Lundin: Yeah, there's an information, sometimes an information mismatch there. There's the communication issues that you talked about. There's also a real geopolitical backdrop to that as well because there's biosecurity legislation, maybe some additional scrutiny of Chinese biotech, the Biosecure Act, all the discussions around there. Does it make it more complicated for you to pitch yourselves to Western partners? And how are you navigating all of that? Three very different relationships with capital, but all of them ultimately about the same question. What does it take to keep the science moving? Let's close by talking about what these leaders think it's all building towards.

32:23Per Lundin: Let's take a look ahead.

32:28Per Lundin: Every one of the conversations I had this summer ends the way that I always like to end them, by asking what success actually looks like years from now for the people that these companies are trying to help. Here's Nerissa Crea of Alterna.

32:43Gene Mack: So I think it ties back to, one, the basket trial approach in rare disease. You know, for patients, this would be something that hopefully helps along with others to set a foundation that basket trials become more and more acceptable as a clinical development strategy. And the ultimate people who win from that are patients. So I think, you know, in my mind, that's really the game changer. But as we think about it at Alterna, AP003 is foundational to thinking about what is the next tRNA therapy we develop, one, but also how do we utilize AP003 across other groups of diseases with potentially other delivery mechanisms?

33:39Gene Mack: So there's possibility, and again, it really ties back to possibility for patients that really have not been well served in the rare community.

33:51Per Lundin: Pair London at Evox is thinking on a different horizon, 10 years into the future for a disease with no disease modifying therapies available today. yeah you know i hope uh dylan that with if i take our huntingtons starting point you know i i hope with knocking out msh3 we are one of the first few companies doing that and i think the genetic data and the preclinical data that supports that target is super strong and if the clinical data is consistent with what we've seen pre-clinically i think we can have a hopefully a really big impact on huntington's disease and so you know looking at the timelines i mean we're starting our clinical study at the back end of next year and so if i look out 10 years hopefully we can be at the point where this is a drug that is actually in the clinic and is used on a routine basis right and you know we're certainly excited by that hopefully that can have a um a really transformative impact on on the disease course in huntingtons at this point in time we're going into stage two patients you know they have started having symptoms but over time i think you want to try to move earlier and earlier and so if you could go in even And pre-symptomatically, that'd be fantastic.

35:00Per Lundin: But of course, that's a long road ahead, right? But certainly just having an impact initially in stage two and perhaps then in stage one, I think would be fantastic. And hopefully we can be there in 10 years' time. For nanobiotics, Laurent Levy puts a number on the scale of what's possible.

35:17Randy Teel: Well, first of all, I think that would be a very good thing for patients if we can bring more cure with radiation therapy. But think about it. it's 60 % of all cancer patients getting radiation. So let's say out of the 20 million diagnosed every year, that's around 12 million. So it'll be hard with just one company and one product to address 12 million patients, even a tenth of it. If you think at NT-PD-1 as an example and the Merck product, I think just recently hit the 2 million patients, but after more than 10 years of usage into clinic, So that will help patients, at least part of them. But in any case, for us, it means that it will, first of all, validate the concept, the overall concept of using nanophysics and helping patients with that.

36:09Randy Teel: That will also bring a large quantity of revenues for nanobiotics and sustainable revenue that will allow us to develop many, many other things in our pipeline.

36:20Per Lundin: And I want to close with Gene Mack at Game Therapeutics. not on a specific milestone, but on how he thinks the whole field needs to behave differently.

36:31Laurent Lévy: Yeah, there's a few things. 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. In 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.

37:12Laurent Lévy: I mean, a lot of times it's best for all parties to 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. And for three decades since I've been around biotech, I've heard about, you know, you've got to publish your failed results. You've got to publish your failed results. You've 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 is no such thing as a failed study.

37:55Laurent Lévy: That just doesn't exist. And there's some wisdom there. But, yeah, 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.

38:34Laurent Lévy: It's how these patients are doing on that particular disease severity scale. It'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. So 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.

39:18Laurent Lévy: So we're doing that as well in our phase two study. So 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.

39:57Per Lundin: And that's it for this special episode of Beyond Biotech. Seven conversations, seven very different bets on how to change medicine. And if any of them caught your ear, the full episodes are linked in the show notes. I hope you'll join us again soon on Beyond Biotech.

40:20Thank you.