 Boom, what's up everyone? Welcome to simulation. I'm your host on sake and we are still at Indie bio demo day number eight We are now going to be talking to Marcel Frankl from gavel on bio design. Hi guys. Thanks for coming on I appreciate it Marcel teach us about what you were just giving your talk about well, so Drug design today is a extremely challenging field because Even when we design great drugs, right? Even when we design drugs that work the problem is that Over time other cancer and infectious diseases. They learn to become resistant to that therapy Right you you might have heard of the superbugs, right and in cancer. You always hear about cancer coming back Right, so what happens is that this is called your ability of the response, right? So when we talk about is durable response of the drug and And the problem is that it's extremely difficult to make drugs that are durable and The reason for that is that then there are numerous ways how a pathogen can develop resistance at gavel on what we do as we develop drugs that can play a chess match and chess match can see What moves right what mutations the pathogen or cancer can do and Design a drug that can overcome those So it's really about being able to design drugs in the fourth dimension right being able to play a chess game through time And that really makes a huge difference on how good and impactful these drugs can be in people's lives and What we're focused on is in designing better drugs Right, so so that's what I was talking about there The other main problem of drug design is that Sometimes the biology tell us tells us that we should go after a certain target, right? There is Something in the system that that's what you really need to hit if you want to make a difference Unfortunately, it's normally extremely difficult to hit those targets So what we're making is a technology that can really allows us to hit what we want Not what we can and hopefully by doing these two things will change the paradigm of drug design make better Therapeutics and finally start curing some of these diseases And so then let's let's walk us through examples. So usually there's like Pathogens or cancers are they're like you were exactly giving us this example They're running through permutations of ways for them to succeed with what their attention is and then to be able to figure out How the body tries to watch and Tackle it as so it's kind of like you said there's a game going on Yeah, there's exactly right, you know, so the truth is this what you're finding in the end is evolution, right? There's that saying life finds a way, right? So what a drug is is a selective pressure in an environment, right? You're selecting Against things that are susceptible to the drug, right? So you're creating a enhanced fitness for the organisms that are immune to that drug and they select that population So what we need to do is we need to be able to see what those possible selection mechanisms are what those mutations are and Design a drug not only against the target today, but against all possible variations of that target And that's what we use our you know unique proprietary and cynical technology to do So, you know and what we hope to do is that that's really gonna have an impact in people's lives And do you take it then the pathogen or cancer you take that into a Into into an environment outside of the body and then you Observe the way that it's trying to permutate and then make advances and encounter those no So this is really cool. It's all done computationally all computation all computation simulate Cancer or a pathogen that's trying to make moves. Yeah, we do this at the molecular level at the molecular level And so so that's why we we you know, we've spent the last I don't know 15 years at Duke building this technology and You know, we finally decide that it was time to spin that out into a company and Really go ahead and use that technology to have impact in people's lives and you know, I think this comes from our personal experience With these diseases and you know losing loved ones And really wanting to do something about that, you know, just I have a you know for me It was my mom She got pancreatic cancer and at first the drugs worked and then they stopped working and we went to five different doctors and we you know Said hey, what can we do and the answer was look the disease has progressed. That's where they use There's nothing we can do about it You know, and it was like no Right, that's an unacceptable reality. That's not the world we want to live in So unfortunately for my mom, there was nothing we could do But I think what everyone in the gavel on team is trying to do is make it so that you know For the people today and tomorrow that that's an aerial changes And take us into the environments where you're actually able to do this to simulate this because this happens to so many of our Like you said of our loved ones I would love to pass more time with let them be more creative let them flourish more Experience more of civilization's progress over time all this great stuff and then okay when you bring this into this to this Simulation environment then you're doing this at the molecular level and how would it I mean this sounds so, you know Let's let's try and make this like as explained like I'm five as possible Okay, you have this pathogen in the environment and you're and you're figuring out its moves and then figuring out how we can do What within the body to yeah, so so you know Think about we really think about these things called proteins, right and the proteins are kind of the work hard horses in your body They're the the things inside of you that do the work so that you can live, right? There are these almost tiny machines. They're these biologic machines inside of you and Normally when you're developing a drug you're hitting one of those right because they're the ones that do the work to allow you to live Hitting them modulates that environment right modulates that work So that's how you can change the environment and change, you know treat a disease or you know help somebody that has Some condition right you change that by messing with these micro robots these biological micro robots Once you find the one that we're targeting What we initiate really is something almost like a chess game, you know in a chess game if you're gonna play well You got to be able to see multiple moves ahead Right and when you're planning your next move You have that context that you're using to make your decision. Yes This is incredibly more complex because it's multi-dimensional, right? It's not just you have a few right? So but it's pretty similar in what we're doing, right? You're looking at What are the fitness conditions of that protein? How does it do its job? How can they maintain its jobs? What possible variations of that shape can then adopt and how can a drug deal with all of that? right and those are the answers that you ask and you really require very sophisticated algorithms to answer and That's what it's all about and it's so then is it the protein that's within the pathogen that you are observing Yeah evolution and trying to see which moves it's trying to make and then the and then you're trying to design the drug that would then Compete against that the evolution of that protein interrupt and interrupt whatever function or you know Sometimes you're enhancing a function there at times you're shooting it off, right? There's multiple ways to deal to try and modulate that That environment, but what you're ultimately doing is if it's a pathogen you want to stop it in this tracks If it's cancer you want to stop it and kill it, you know, and if it's another condition then it's more You know sometimes you want to increase something or decrease something, right? You can think about how to immune diseases right where it's the body's immune system there You don't want to kill anything. You just want to you know calm things down a little bit All of these can be modulated by designing better drugs and You know, that's really what we want to do. It's not only about Toxicity right we actually want to design drugs that are gonna help people right make people healthier and live longer and you know Especially I was just telling you for us. It's about making sure that People are really having better lives and not losing loved ones diseases, right? You know cancer is almost like the bogeyman right when you're young you believe in the bogeyman Once you start getting older The bogeyman changes its name right every time that you feel a lump that wasn't there in the back of your mind. You're like Well, you know Maybe it's something that shouldn't be there, right? Man if you have experience with it, you know that sometimes it's like that one day You're fine and one day you're not fine or someone you love has through that So having something that can treat that that can overcome that that's really all we're about Yeah, I'm so fascinated with the simulation environment of analyzing the the proteins evolutionary trajectory and how it's trying to have its What it wants to achieve done within the body and how you can then Simulate the the drug so you're simulating the molecules that are then competing against and you're also trying to deliver it directly to where that protein is for it to get either inhibited or yep to have to enhance something that competes against it this Yeah, exactly This is so freaking cool. Thanks. Yes. Yes Many a lot of why we call the show simulation is because of really cool things like this like all these different aspects to these Biological simulations that I mean in many ways like that civilization and the universe could be similarly within our bodies We can recreate the simulation environments to see how we can tackle pathogens Without even doing it outside like taking having to do it outside of the body, but actually just simulate it Yeah, yeah, you know, we do eventually take these and test them right because Still today, right? No simulation is perfect, but the idea is to get to a point Where you know Whatever you're predicting is coming true and the most exciting thing the thing that really took us from being academics To being here and you know is that idea that? You know, we're almost there right we're starting to see these things so I'm actually still academic finishing my PhD right now, but You know, we're starting to see this result or what we predict is what's coming true when we test it And when you start seeing that it starts giving you a lot of confidence that you can actually change people's lives and that's That's what it's all about right it's about bringing about change And then you guys make the the simulations better and better make the the drugs compete better and better And then the idea is to deploy one to compute to actually for the Physically use and yeah, exactly and which one would that be to compete against you guys have any idea so We we we work in two different ways one a way is that we work through partnerships where normally a partner already has a initial molecule That he's trying to optimize and we help them optimize that okay The other one is we have our own pipeline. Okay in our own pipeline We're using your unique ability to design custom and ideal drugs to target drugs that other people can't and There's a whole class of proteins called undruggables Undruggables. Yeah, and and they're kind of like, you know, sometimes called the holy grail Medicine because we know that they're important. We validated You know using things like CRISPR assays and we validated that they matter and yet We haven't been able to hit at them because they've remained undruggable. That's the name, right? They've they've been resilient to other methods So what we wish to do is show that we can hit them and by doing so that would really change medicine and change what we can do For the first time we want to be able to hit what we can we would be able to hit what we want and That's gonna really make you know bringing a new age of medicine. So we're very excited for that. Okay. Okay, cool It seems like yeah, the trajectory is Yeah, both having the Organizations that are currently trying to figure out how to better deploy their own Drugs working with them Computationally and also on the with your own pipeline Exactly to make and you think it the pathogens to compete against are which ones for you guys first, so, you know Personally, we're starting pancreatic cancer pancreatic. Exactly, right as I told you this is You know a decision made From personal reasons, right? The you know as I told you the story about my mom, you know, there's a little bit of You know, you could call it a vending going on right there's this idea that we saw how terrible that disease is and You know, I don't think I think it's terrible that anybody has to go through that, right? So we want to start there But we're gonna expand and with partners We're doing both Infective diseases like the superbugs as well as cancer so go in both ways Okay, and then the For for a company trajectory then for people that are wanting to work with you. What are you guys looking for right now? So right now we you know, we're very fast So it takes us about three weeks to go from the beginning of a project to the completion of that project So the drug design process takes three weeks in our computers So and that and that includes the whole thing from hit all the way to what's called a lead Which is you know from a very initial design all the way it's something that we think is gonna work So we're always open for more pharma companies to partner with us so that we can help them develop better drugs as well You know, we always The truth we want to have the biggest impact we can so we really want to work with everyone we can You know and in the Bringing in more talent, you know the thing that's most important for us is people who believe in a vision of a World where these diseases are under control and treatable and you know We don't have these superbugs bringing in pedemics, right? It's about having a shared vision about what can be done through these technologies Coupled with the skill to make it real and I think that's what we would be looking for Yes, yes, and then what would be like the simulation environment that you're Working in like what is the software that you so these are proprietary softwares that you guys made that that we that we built Yeah, cool. So yeah, so these are all proprietary software They build from a open-source software called osprey that we helped develop as academics. Okay, so For instance, I have publications using osprey's my co-founders developed osprey And this was all developed. So we all come from the same lab Which is Bruce Donald's lab at Duke University? We are spin out of that lab and then that lab they developed osprey Which is an open-source version of this code and what we did is we introduced new features redesigned pretty much everything from scratch Made it about a million times faster And you know beyond that also introduced some new things that were required to make it in a pharma context something that would be successful in a pharma context and You know just continue to build You know the technology we have a belief that we're great today but you know These diseases are a huge challenge and you have to continue pushing the technology So that's an area that we're all very dedicated to it's continuously building the technology to solve these problems I'm excited to see where Simulation software can help us not only with like digital twins of the body and being able to run calculations of Preventing disease pathology this type of stuff, but also doing things like making digital twins of the planet and Simulating the evolution of our whole species all these types of things simulation environments are very fascinating I'm glad you guys are leveraging them for this Marcel. Thank you very much for thank you really appreciate it Thank you. Thank you. Thank you. We would greatly appreciate everyone to give us your thoughts in the comments below on that So thank you very much for tuning in Also, do check out the links in the bio below Gavilan design bio design also definitely check out the links to Indie bio as well Check out the links to simulations will support these artists these entrepreneurs these scientists These leaders in our community support them help them grow and go and build the future everyone manifest your dreams into well Thanks for tuning in. We'll see you soon. Peace