The Crazy Science That Might Cure Brain Cancer | Aaron Edwards (Part 4/4)

Intro - 00:00:06: Welcome to The Biotech Startups Podcast by Excedr. Join us as we speak with first-time founders, serial entrepreneurs, and experienced investors about the challenges and triumphs of running a biotech startup, from pre-seed to IPO, with your host, Jon Chee. In our last episode, Aaron Edwards talked about leadership growth, the importance of humility and feedback, and how documenting institutional knowledge can become a startup secret weapon. If you missed it, check out part three. In part four, Aaron shares the origin story behind KiraGen, from a class project at HBS to launching a venture-backed biotech. Working to overcome immune suppression in Solid tumors. He dives into their contrarian approach to CAR T-cell design, how they found early product market fit in glioblastoma, and why staying focused, running lean, and building with discipline has given the company real staying power.  

Jon - 00:01:14: So, you know, you're at HBS and you have this wonderful Nucleate experience. You're seeing it kind of like in action in a place where you're like, okay, maybe we should do this for real. Talk a little bit about that point, that journey of like, we're going to do this for real. Like, how did you come together with your co-founder?  

Aaron - 00:01:37: Yeah.  

Jon - 00:01:38: Company origin. Talk to me.  

Aaron - 00:01:39: 

Yeah. The Origin story, finally.

 Jon - 00:01:41: Yeah, yeah, yeah, yeah.  

Aaron - 00:01:42: And finally, this is, it's really important because part of KiraGen is my relationship with mine and all our experiences. So KiraGen formed from a pitch deck exercise.  

Jon - 00:01:52: Yeah.

Aaron - 00:01:53: So, so, so going, you know, we talked earlier about the learnings. We had a lot of learnings and we became best friends in, at Bluebird and Beam because we were always asking each other, why is, why are we doing this? What is the strategy here? And now looking back on it, we were forming what we would do if we were ever given the chance to do things on our own or, or differently. We're just given any, any opportunities here. And I called Ryan up. We worked at not only Bluebird together. I was an early employee at Beam Therapeutics, brought Ryan over once we sort of evaluated base editing and T-cells. So our backgrounds are cell therapy at Bluebird, getting to see transformative outcomes for CAR T and leukemias and some lymphomas, but challenges, translating that to Solid tumors for many different reasons. We are already kind of getting our feet wet there, but really see again, the benefit of frothy markets. We saw so much science. And it was really great for us to get access to that, but also learn that we need to also be able to know how to move things forward and make decisions. And not that they didn't, but that was something we really wanted to clime in on. And how would we rationalize decision? At Beam, it was a transition of, now you could go into what we call CRISPR 2.0 and say, now that you're not a genetic scissor, you're not a nuclease cutting, you can use base editors or now others to what we call the pencil and eraser at Beam. I don't know if it's trademarked, but that was what we used to say colloquially. And it's great for now. The company's really focused on in vivo disease correction. It's an amazing application for it. For cell therapies, it actually allows you to think about how to split the script on how to design these modifications on cell therapies that maybe can imbue it with different functionalities that an artificial receptor or something else with a Nucleate's cannot do. So at Beam, this was multiplex editing. So you can now make many modifications without really altering the viability or health or having these genomic sort of aberrations by making too many cuts. So at Beam, we learned, okay, you can make many modifications. How would you apply that? And we did it with a multiplex edited CAR T for T-cell leukemias. So this is important because you have to not only have a car, you have to remove the surface molecule that the car is targeting because it's targeting T-cell leukemias. It's a great application that opened our eyes to say that was just the beginning. What happens when we think about moving beyond, this is a quad-edited product. That was the first time a healthy donor drives those allogeneic edited product. It now is in the clinic. It's led to some CRs. Amazing time. What happens when you start installing multiple edits? You know, when you take like a George Church, David Liu paper saying we can make 200 edits in a cell. What do you do with that? And that was part of KiraGen's story. And this is nothing against that. The tech now, so talking about tools, the tools to create these really cool things is not the bottleneck. The bottleneck is application and the people and how do you make something that people should care about and can be developed to take into the clinic. So when I called Ryan up, he had gone to get his PhD, really focusing in on can you go into maybe a different direction, use multiplex editing to think about solid tumor microenvironments, which are low in oxygen, have all these things that are upregulated to turn your immune system off and our immune cell-based therapies. Called him up and said, hey, let's put pen to paper on something that we think is cool using our expertise. Is it still differentiated? It's part of the pitch deck exercise. It's like NBA 101. Is your idea differentiated to a landscape? Then the best thing is to build in something new to the company. So long story short, KiraGen is new. Most people that are working with nucleases or these sort of artificial strategies, if they are encountering a suppressive microenvironment, they try to make these T-cells or NK-cells more potent. So you're trying to break through the suppressive barrier, which is fine and dandy and will work in some applications. It probably can't and should not be applied in some sensitive areas like the brain because the inflammation in the brain is really not tolerable. And we said, okay, that's one thing, but you're still redirecting function and compensating for these sort of signals that a tumor or all these other suppressive cells are spitting out at your cell therapy. So you redirect with a cytokine or you try to change the potency in a different direction. We said, okay, people are doing this because they were limited maybe by the 1.0 generation. We are not limited by changes. So let's first principles approach. What's the problem to solve? Let's not do other people are doing what's the problem. T-cells, NK-cells, gamma delta cells, whatever it might be, sense these negative signals from receptors on the cell surface. And there is a way, it's not as trivial, if you can knock out those receptors only and actually create this what we call TME suppressive protection layer that just prevents the cell from being suppressed. That's really the crux. Beyond some physical barriers, which are still present, there are a lot of examples where a T-cell can get to the tumor site. It has the ability to also address tumor heterogeneity via next-gen targeting strategies, and it gets turned off almost instantly. It might start signaling and it's turned off. There are 50 to 80 different pathways in those Solid tumors that are upregulated. So if you are a PhD student and you work on TGF-β, which is a common suppressive factor, and your tech is one receptor that's going to block TGF-β, that is really cool, but it's not going to be enough. Our thesis on this pitch deck was that you need to address multifaceted TME suppression, just like approaches in the antiviral space, in the antibiotic space. You need to really shotgun approach it almost to address many different non-redundant pathways. That usually tumors use to evade whatever strategy you're after. You can't just block PD-1. You know, the biologics space is now challenged by not being able to give people anti- CD1, CTLA-4, LAG-3, because you have toxicities from these molecules. Well, for us, we prevent suppression before it happens. So there are ways that are not trivial, which is part of the second part of the company, to knock out just the receptors that don't alter potency, but allow a function that we know works in heme, at least to some extent, to finally translate to Solid tumors because the CAR T, CAR-NK, whatever it might be, can get there and continue signaling consistently, persistently. Durable functionality is our goal, but it is very different than what people have thought. So not only is the biology of making this many edits very counter to where the field has gone in the past, People said, how would you ever decide if I told you that our lead product is a six edited RT-cell? Someone says, okay, you just told me that there are 80 pathways. How do you choose? Well, for us, it's not screening. Screening is cool. We are design optimization. And now we have a machine learning model that rationalizes that for us. But it's not screening from scratch, right? This is a huge shift of every company needing their own novel protein, a novel pathway to block. Now, our protections around the combination itself and how we're protecting these cells against suppression, and we've been able to rationalize it from this list of 50 to 80 down to, say, six. Very clinically validated via things that we know in the clinic to work. It's biologically sound. All the regulators know the pathways, but no one's had an approach, one, an approach to address suppression, but two, a way to make you care and believe that that combo is what should be going into that space. So that came together. I'm getting back to the entrepreneurship, and we'll talk a little bit more, but we were just an idea. So we made a pitch deck. And then when the exercising class ended, we kept working on it. We were like, this is cool. And 2048 Ventures, who has a biotech studio program that is very similar to what I call Y Combinator, but very focused on biotech, gave us our first capital. And they believed in our idea. It was well-vetted, of course, from our background, but gave us a set check size. We filed IP. We got into the lab on campus, so the Harvard's Pagliuca Life Lab. As students, you get free access to a shared bench, which is super helpful, really great. And now that we're a real company there, you get some subsidized help, but also this infrastructure where you don't have to buy everything from scratch. But when you do need specialized equipment, you can go to Excedr and lease things that we know are our workforce assets. So it allowed us to get in and be capital efficient, right? So we were doing something that still to this day is very counter to what people think should happen. People spent money in cell therapies, and they are running to either in Vivo or ADCs that have other advantages or selling points about being cheaper or whatnot. We said we can do it differently. We have this experience. What we do is using validated processes, reagents, and methodologies, but we're putting the puzzle pieces together in a way that just has not been done before. But we are building upon science in the past. This is important because we do not focus on binder design. We do not focus on all these other things that maybe we have to partner with someone on. But the solution to Solid tumors is not going to be one thing. Just like our CAR T-cells are not one piece of technology, we need to be building upon others. So I'll get to this, and it goes back to the company formation. Even if we had all the money in the world, our lead program is in glioblastoma, which is an extremely aggressive and rare brain cancer that has very little progress has been made to date in the last 20 years getting therapies that really help patients. It's inevitably a death sentence, but in the brain is where all this progress in CAR T has been made to date, which people don't really think about. Really, a lot of cell therapy success has been very little in the solid tumor space, in Glioma and some gliomas. There has been activity, like actual activity that's measurable. And so we are working upon others to build finally upon not only clinical success, even if transient, but we are addressing known problems. So not only do we have this kind of, we have a crazy contrarian sort of biological approach, which is this multiplex editing, but it's grounded by solving known clinical problems that have already been identified to durability in these patients. So it's not zero to one anymore, which people don't really see. It actually is, it's one to two. And what we found, which is exciting, and I'll pause for a second because I can go on forever. We found a really perfect product market fit as an early stage company. But it was timing. It was a pivot. We did not start with this. Nucleate helped along the way. And I have a story here about that. But the perfect product market fit, but in an indication that people are scared by, rightfully so, if you're a VC or other funders, nothing has worked in the past. And so it is a product market fit with an indication people might be scared of. And also in modalities like ex vivo cell therapies and gene editing that aren't super in vogue. And this is a great lesson for anyone out there, but it is our background and expertise. We did this company because we didn't see anyone else doing what we were doing, and we didn't think people would do it. And now, if you can weather the storm, if I can get two minutes with you or on this podcast, if people are listening, to tell you why, if you can, for a minute, take away the historical challenges of glioblastoma, it is perfect product market fit. We're addressing challenges that are known problems to durability, not functionality, not efficacy in getting zero to one. And so that gets us really excited. We found a spot to not only thrive, other people are not in, but also this non-potency enhancement-based approach is best suited for the brain and other spaces for now. It's actually a great proving ground, where there's not a ton of competition yet, and we think it's actually biologically differentiated, so that when we get to that first in human, we can spread in tons of different directions, because most tumors have these suppressed environments. So lesson, I'll wrap that up, is know, as a founding team, what your skill set is. And even if everyone is going into in vivo autoimmune CAR T, which is amazing, and every tool should have its application, doesn't mean you shouldn't be doing what you're doing. People will tell you to go in other directions, and it's usually best to stick to your guns and do what you think is best for you and the company.  

Jon - 00:15:51: Spot on. And I think there's a lot of advice out there. As democratizing as the internet can be, there's a lot of advice that's being given. But I think ultimately, as an entrepreneur and leader, it is upon you to make the judgment call on what advice to take. It can be hard when you're speaking to people who have been there and done that, that you might be like, well, they've been there and done that, therefore I should do what they're recommending. But at the end of the day, everyone is trying to look into a crystal ball. No one has it figured out. So sometimes you've got to lean into your own judgment, expertise, and taste. For me too, like, even just starting Excedr, I was just so many times where people were just like, what are you even doing? Like what are you even doing? And if I had taken their advice, I probably, would have thrown in the towel, like way earlier. And so, it's not to say that all advice on the internet is bad. If you take everyone's advice, you're just going to be like treading water in place and pulled in like a million different directions. But it's for you as the leader, founder, entrepreneur, or whoever, wherever you are in your journey in an organization is to set that North Star and be like authentically you and lean into your strengths, which I think is critically important. You mentioned that Nucleate helped you come to this conclusion. Talk a little bit about that.  

Aaron - 00:17:17: Yes, I was going to say, even if you didn't ask. So a lot of Ryan's background was in non-small cell lung cancer. It's another suppressive. All of these Solid tumors have suppressive microenvironments that this layering strategy can be beneficial for. Data looks good from his PhD. We're like, okay, if we wanted to create a similar program, take it to the next level, maybe that would be something we could do. So we were sort of pitching that as an idea throughout Nucleate. And it wasn't landing. The science was cool, but the biggest difference, we knew that this non-small cell could work and would make CAR T better. But the logic from A to B, if we remove suppressive barriers from five or so edits, will it lead to this outcome in patients? Was not there. And crowded market. So for us, we were being asked as a pre-pre-zero seed company, basically, how to stratify patients. And we're like, I don't know. Because we haven't even gotten there yet. We're just trying to find a space to apply it and proof of concept data. But I will say for Nucleate, and really shout out to them, one of our quick pitches right before Demo Day, which is like the penultimate time you do the demo, it was a big flop for me. It just didn't land. You could tell. I could read a room. It did not land. And then afterwards, I had a long conversation with some of the judges and told them about this glioblastoma data that was starting to come out in March of last year, where two groups showed independently, 100% response rates at the time, these Glioma patients, these MRIs were showing tumor shrinkage in glioblastoma patients. And they said, just try it once. Maybe not for Demo Day, but like try just shifting your story to Glioma because that's an interesting, it might be scary, but like that's a story here that people might care about. And the more we dug in, we liked it. That the night before Demo Day, I stayed up until about 2.30 in the morning changing all of our slides. And I did do it for Demo Day. And I pitched it the first time and we won last year because it was a story, right? And the more we dug into it, it actually did make sense. It wasn't just a good story. The lesson here is know the problem you're solving. It was even more so not just in the market today, but for what we're doing, we had to prove that people should care. And showing that we can solve a problem that is known, that has been elusive for not just many companies in biotech, for cell therapies of if you do this and you actually achieve what you want, will it lead to what you think it's going to lead to? For Glioma, yes. Like something happened, it worked, it didn't work for very long. They know why it didn't work for very long. And we solved that problem. Like that there is such an opportunity for us to take advantage of, but you have to go out there and start pitching and being nimble to be able to change where you might apply your approach and be willing to. That is a good example of listening. We listened to those judges and took a really close kind of careful examination of the story. And we're like, yeah, we should try it, right? Be willing to be flexible. And that was a great example of listening and pivoting. Where we have not pivoted is thinking when a VC comes up and says, are you in autoimmune disease? We go, no, there's nothing to do with what we're doing, right? It's not a product market fit for what we do, which is fine. We are not in vivo, CAR T. We are not doing all those things. Maybe one day we can get there. But what we do well, we want to be known for. And we don't want that to be confused by any shifts in where money or interest might be taking us because we have conviction that we have really something special here. 

Jon - 00:20:59: And focus is important. Underrated. Focus is underrated.  

Aaron - 00:21:05: Yeah. And that actually, I have a ton of little tidbits I love to get out today. But the inability to focus and get something to patients is a challenge. That rationalization, not only why we have this platform and machine learning model to rationalize in the lab, why you don't have to test 10 billion permutations to get something to move forward. But the focus to know when people ask what success looks like for you. Of course, as any business, you want to say commercialization or some revenue or whatever it might be. The way to help people, if that is your mission, is to get something to the clinic. Focus on getting something to the clinic because even though it might not make you money yet, you can start helping people from the day one that someone is treated. And that is powerful. If you can get there, it would be a blessing to get there and have the choice to see what's next for the company. But that is really hard. And where people think where AI can come in and all these different things, it is finding ways to, for startup companies like ours that don't have the $100 million, can we use AI and other tools to still get to that first human inflection point without doing all the other things that have been done in the past? It's really top of mind for us.  

Jon - 00:22:23: Absolutely. And I think I always work backwards from the only, it goes back to like when you were balancing school athletics, but something's got to give, right? Something's got to give. Same like, this is why focus is important. Because if you're, if you constantly have your head on a swivel and you're taking your eye off the ball, you end up being like lukewarm. Okay. And a bunch of things. Yeah. Focus is like saying no to a lot of things.  

Aaron - 00:22:52: This is going at the money problem. So having too much money, you chase the shiny thing. And for a field where tech is like turning over every day, there's a paper coming out. You're like, oh, guess our program's canceled. You have got to push something forward because something has to go to patients. For Glioma patients, they don't have time to wait for us to have something that is 10 billion permutations tested, etc.. But we can improve. And that's what lifecycle iteration is. You can always be doing science for science, but you can't do that. It's really important for us. Some people might want to do it. You have to focus. Focus on what you do best. If we can be known for making an impact on brain cancer patients. The future of our company, we can decide then. I mean, obviously, we have strategies in place, but... We want to do that. And that's what we can be known for. And then if we can do more in the solid tumor or liquid tumor space, albeit that would be a cherry on top.  

Jon - 00:23:52: Absolutely. And, you know, so now you've, you've gotten your conviction, you're riding the high of winning Demo Day. You mentioned that like, you got your initial lab set up. Can you just like talk about like your experience of like, just like the nuts and bolts of like early company building for you? Like, you know, you have a blank bench, you got to start recruiting. You got to start fundraising. You got to start outfitting the lab. Talk a little bit about just like the nuts and bolts of that.  

Aaron - 00:24:20: Yep. Yep. So some advantages for us, for sure. Ryan, what Ryan was essentially done with his PhD science and he was just writing his dissertation. So he was free to go. We got funding from 2048 earlier than we thought. So I didn't, I didn't say this earlier, but we did this pitch deck because I went on tandem. We did this pitch deck and someone said, you should talk to people about that or somebody. 2048 was the first people we pitched and that we were just, it was just really fortunate. It was fortune, fortune, fortune, fortune. So they put our first capital in and we had to then decide those consequential decisions of how do we spend this money? So I still had a semester left to school, and so did he technically. He was in the lab on campus setting up, I don't want to say the bare minimum, but we knew where we needed to be. We had limited time. We needed to file IP and do a little bit of lab work to prove out these sort of main pieces of our hypothesis that we knew could be done to get more money. So we did a lot of work the first six months. He mainly did most of the lab work. I was finishing school and doing some other things, trying to set the stage to fund more. So 2048 helped us set up the first round of our pre-seed, like the first tranche of our pre-seed round. And then we got a million on top of that. And that allowed us to finally say, okay, we can build with an eyes towards mouse data. So every time we've thought about money coming in, it might not have been an exact amount more or less than we anticipated, but with the money in, where do we need to get? And we need all eyes focused on getting there. We can worry about some of these curiosities later if we have the funding and ability to do it. It was zero to the first check-in. It was how do we get some proof points, like minimal proof points that also came with lab setup, right? It was like buying things that... The Life Lab definitely did not have, which is fine, right? They can't have everything for you. And then the second phase was hiring. So we, I would say, opportunistically hired people that were experiencing some reductions in force that were great for us. Because most, I guess, four out of six of us have worked together in some respect in the past, which is really cool to now experience multiple versions of people working together. But making sure that new people coming in are not excluded, very, very important. Now that we had this kind of million extra in the bank, it was getting to mouse data, which doesn't happen typically. But we were like, we've seen this before. How do we do this? How do we get there in as little time as possible? Even if it's not as translational as you want, that's the inflection point that can build more on top of that conviction we have. And so the last year has been, what can we do within the confines of what the Life Lab has and doesn't have, which is totally fine. What groups like Excedr can we use to make getting in some of this equipment that we know has to come in? How can we do that as cheap as possible, at least on our limited constraints? Even if long-term, the ticket might be larger, temporarily, that impact on each paycheck or each bill cycle is so important. So we spent the last year getting team members in, one, either opportunistically getting them in or just being able to reach out to people we always wanted to work with again. It was really exciting for Ryan and I to go back to school in our different ways and to have people say, we can't wait for you to start a company. We weren't thinking about it, but that was the early motivating factors. People saw something in us before we saw it in ourselves. And they would say, when you start a company, let me know. And that was really cool. Not an ego thing. It was really humbling and exciting to say, hey. We're starting a company.  

Jon - 00:28:16: Yeah.  

Aaron - 00:28:16: Do you want to come work for us?  

Jon - 00:28:17: The call's coming in. You ask and you shall receive.  

Aaron - 00:28:21: Yeah, and that's cool. Even if some people aren't doing exactly what they might have done when we were working in their past, the implicit trust is there. I know Ryan, and I trust Ryan because we have been through so much together that I can teach him some business stuff and vice versa, but he can do day-to-day science stuff. But the people in the lab, we also know them. And so hopefully it's allowed us to know they will tell us when something is going bad because we know them. And I think that can spread out. So it was getting a team in on the wet lab side, seeing if there were opportunistic hires seems a little bit sterile here, but seeing when their people were able to come join us because we had a million dollars in the bank. We're doing something crazy. Like it's a big risk to come to a startup with uncertain features. And people took a risk and jumped in, dove in, and we now have gotten to that milestone. Not only in the wet lab, but part of that story around rationalization, decision-making. The ML side is not a hand wave, right? Like we are not trying to solve all biological problems. We now have Tessa Green, who's our head of machine learning in, specializes in machine learning for biology. We legit have something that can start rationalizing and making these decisions. And maybe not for our first program, it'll help maybe confirm these edit selections we make. But in the future, you really can have these platforms that are turning out the concepts that are well vetted. So you can put less and less capital into the wet lab data generation and have the ability to maybe be that service platform. If we can't do something internally, how can we enable other people's programs? We would love to work with others that are in other cell types, other indication spaces that we can't do everything. That's the lesson. Even if you're a platform company, you can't do it all. So focus not just on our program, what pipeline we want, but this is important for the team to think about. How do we have conviction around our biology and approach in a way that also is democratized? So we can democratize via licensing and some money, hopefully, in partnerships to make sure other people's programs are also given the best chance they can to succeed. If we think we have enough conviction about what we do, we can't keep it to ourselves. We shouldn't. And so being able to build that over the year, I mean, it has been challenging. I tell you what, I mean, not only from the VC side, everyone is having a hard time fundraising, but it is penny pinching while not minimizing what we do. Like we have to just really be careful about every dollar that is spent, making sure it's moving the needle. Science for science cannot be done at this company and cannot be done at other companies right now. When you're trying to do things more efficiently, but also don't know if you can access capital immediately when you need it. And so we've had to have hard conversations early on that have been, I think, the best way to build teams and trust and respect early is for leaders not to say everything's great. To say, hey, this is the environment. You might not have all the exposure that I now have as part of my job to see what VCs are telling us or where we see the landscape. It's my job to communicate that to you. So you know, again, your role, whatever it might be, that there's synergy. We're not repeating stuff to hopefully be as efficient as possible. But to also make sure that they have the confidence in me that I can bring in more money. My job, as I describe it, is to enable everyone on my team to do the best job that they can do, whatever that might be. Right now, it's bringing in capital and keeping us on sort of a trajectory. Maybe when we finish this raise, it is building in the notion, you know, templates, like it's operations, whatever I need to do to enable others to do their best jobs. And so it's been challenging. You know, it comes with ups and downs, but to get these signals from others that see what we're doing and what we're building and to have opportunities to come on podcasts like this and talk about the story, right? The storytelling is half of it, getting out there. And then that final piece, this type of platform work or podcast stuff is also helpful to access maybe people that don't know your story. There might be people out there that want to support Glioma work or our mission broadly, and you just had to get out there in more ways than we have before, right? You can't just go to the four people or four VCs that you might know locally. You really have to expand the horizons, and that's okay. 2048, I admittedly didn't know them when they gave us capital at first, and they have been the biggest supporters and champions of ours from day one, walking us through early stages of building, having that support. And now that we've built, you can see there are different, layers of investment in VCs and firms. And it doesn't always have to be what's typically called the blue chips. They're blue chip for a reason. There are other sources of capital that aren't even the VCs. You know, we just got a pretty significant check size in from a family office that has a really invested interest in a specific disease space. So when you're thinking about these challenging times in the market, not that money should guide different directions if it doesn't make sense for you. But think about how do you find those family offices or others that might have alignment with what you're doing and be a bit more of what they call Patient capital. Patient capital, their return on investment is just a little different in how they measure success. And if they have a specific interest in what you might be able to apply it to, it's a great opportunity to get some proof of concept money in or something to really give a startup the chance to build that data set that you need to finally get out of this valley of death, what they call it in textbooks and get access maybe from those blue chips, if that's who you want to get money from. It is really being creative. It's been an adventure so far. I had to thank my Ms. Frizzle's again all the way through. HBS has been amazing. I have to give a shout out to before I forget. Reza Satchu is a professor at HBS that has been doing a lot of work on entrepreneurship and founding. And he started a class right when I joined about founders mindset. And there are professors like Reza, and others that are. Trying to not only instill this sort of foundational curriculum, but get people to think about how to start companies, like therapy for founders, and really give people that risk appetite that definitely exists in the Bay Area, but is a little bit different of a story here in New England. That type of infrastructure and ecosystem is not as active, I should say, as you might think it is, but it takes all of these pieces. So raise the having founder mindset and really teaching us that you can take risks, and our downside risk versus upside potential, and all of the work that professors are now doing to teach biotech people. In fact, I had biotech cases. I just can't be more thinkable for people that have been this Ms. Frizzle's along the way that have allowed me to know and learn and teach me things that I can now instill and install into the company. It's just been a great journey, and I can't wait to see where we go in the next phases. And shout out, I know I've said exceeding multiple times, but the pieces of equipment that we have to do in CAR T are not cheap, but you have to have them because they are the workhorses of how we generate data. And even though we are at these shared lab spaces, they are not all cell therapy equipped. And so you do end up having some specialized equipment per company. And so finding ways, whether it's creative funding sources or people that have different business models, like exceeders, to get you access to the same type of equipment you need as a startup to thrive and to sort of pattern match with other companies that have a lot more funding or time are critical. And it's really great to have people starting to fill that gap. With whatever it might be, AI tools, or again, leasing models for companies to succeed, because the science is there. We just need to be able to be given the chance to get where other people have in the past.  

Jon - 00:36:55: Don't make me cry, Aaron. Don't make me cry, man. And I appreciate the kind words. And it's like, ultimately, that's our mission. And I think everything I've heard about the level of discipline in which you're operating in your company is like... So commendable. Because like, for example, you talked about like, de-risking at every stage, and making every dollar count. That's not sexy. But it's important work. It's important work, because at the end of the day, the patience, you got to remember that the time is of the essence, right? And it's important work. And it's also like, it's like, in this environment, that's kind of how you need to be thinking about it. Like, you got to show progress each step of the way. But I love the out-of-the-box thinking because I think I always think about, you know, CHOP supporting the Children's Hospital.

 Aaron - 00:37:46: Yeah.  

Jon - 00:37:47: Supporting Spark. I think it was like they gave them like 10 million bucks. And that's pretty much all, like all Spark got, but it's a different source of capital, right? Of course they had a vested interest. I think that technology and like they have, they do a lot of the technology overlap and interest and patient group overlap was massive. And I think for anyone out there who's thinking like. Oh man, like the VC traditional spigot is completely closed. It's not completely closed, but also there's like spread your wings and talk to people. Exactly what you're saying. It's like you'll never know who you might bump into where your values might align.  

Aaron - 00:38:27: Yeah. The unconventional tip is no shame in saying, I talk to people, even if I'm out with a group of friends, if something comes up for them, we're fundraising. Do you know someone? You end with like, do you know? Add something to every call about, could you make a connection? Do you know anybody? And that source of, yeah, it's not just funding. We've done this on the clinical side. For glioblastoma, it doesn't matter. It could have been any other indication, but for glioblastoma patients and this really complex therapy we're making, we are not the people to take that in the clinic. We wouldn't have it anyway, but we can now work with these academic centers like UPenn who have taken this into the clinic before and say, you are the team. And they're not only ways to say that is a CD risking from the clinical perspective, they should be doing it in the first place. There are ways that you might be able to partner with them. They have manufacturing in-house that might be cheaper than some external sources. Or this is a tip for those out there. There are a lot of companies, especially in cell therapy, like ours, where the cost is always a concern. There are CDMOs that are trying to be creative with how they partner. And I don't want to call it too many because it's going to be preferential. I just want to give one example. Sorry, this is the one chosen if you're in another company, but Thermo. Thermo is there are many companies that do these sort of accelerator programs that now have the infrastructure sort of start to finish that you can approach. It doesn't have to be them, but if whatever company has that infrastructure available, maybe they take some equity in the company or some other creative ways or downstream payments. So you can actually do something at a much lower cost than it has ever been done before. Because now there's creative partnerships. You have to do that. You have to be creative, but that's a positive. Be creative, know how to deal with those opportunities. But if you continue to think about whatever it means for you and your business to be creative, the benefits are going to definitely come in the long run for you. Whether your company is alive at the end of all of this or just being able to have multiple options finally to choose where your company goes. So be creative. You cannot do it alone, even if you have the money. Partner with people to do things because together you can finally take advantage of these tools that are now going to have the potential to cure, lead to cure outcomes or at least impact in these populations that have not had. Success or been fortunate to date.  

Jon - 00:41:02: 

Yeah. And I love what you just described. It's like finding people who have like aligned interests with you. And I'll bring it out of science for a moment, but like in the early days of like software startups in like the Bay Area, like law firms would take a little bit of equity, but then you have, you pay less in legal bills, stuff like that. Or there were firms that were like design agencies that would take a little bit of equity, but they would help design everything that your app needed, your mobile, your site, yada, yada, yada. And I'm only giving these examples is because like, think about the stakeholders in your ecosystem or your problem set, speak to them. If they have a vested interest in seeing your success, they can support you in other ways outside of their services.  

Aaron - 00:41:50: Yeah, and they still exist. So again, to speak to more people than the two of us, for biotech, all the top firms, all the firms for legal still have those type of arrangements because they know they have to. They're good, so they eventually will charge money, but you might have an offset up to a certain bill amount because they show potential in you, and that's the way that they can create future money. But I think the aligned interest goes a long way. When capital was flowing just into biotechs, the academic industry interface was not very healthy. Not just in how it functioned, but how they viewed each other. Because as a company, you might want to come in and say, get the trial and get out. But what we're doing with our lead program, if you're sharing IP or there's some aligned interest, one either on the patient population they treat, or if you're sharing a technology you're building on top of already, they have a commercial interest as well. And so it's a win-win. You help patients that they care about. You have a program as a company. And they get returns that come back. And that's how it should work. And if it works and expands and you like that model, you can expand it. You're really thinking about and being okay sharing a bit of the pie. You've got to share some of the pie. If there's pie to be shared, I'm fine sharing the pie. If there's pie to be shared, and if it's more than just blueberry pie, there would be cherry pies if we get into other spaces, right? It is a win-win. And you have to think about that. And I think it's really, it's again, not just flipping script on science, what we do, but showing people, not just because of the markets, there are different ways to go about running companies, scaling and growing. So ask. Don't be afraid as a company. Even if it's early stage creation, the one piece of advice I love ending on or getting close to ending on is ask people for help. People want, like in my shoes or whatever, they want to help others get to where they are. And the worst thing you can do is think that you need to keep your idea or what you're doing secret. Like your secret sauce, your differentiator should be more than what you say on a podcast or have on your website. It should be your team, your IP, all these things together, which make you your competitive moat. But if you don't go out there and take some risk, ask for help if you're struggling, like it will make it 10 times as hard. So people told me that in the past, and this is my chance to tell everybody of ask for help along the way, and it will come back to you, you know, leaps and bounds. 

Jon - 00:44:29: Absolutely. And honestly, Aaron, like I'm so pumped to just like play like a tiny little part and like support where we can. It's like, I'm just so excited for you guys. And I love the contrarian approach. I mean, look, that's where value creation is. You got to do things differently, honestly. Like if you're just doing more of the same, what are we doing? What are we doing here? Like, why are we even trying? We got to do something different. And, you know, just hearing everything, I'm just like so fired up for each of the next stages for KiraGen. And as you're looking out one year, two years, what's in store for you and what's in store for KiraGen?  

Aaron - 00:45:06: Yeah, so we have this lead program I've talked about in glioblastoma. It's a six-edit CAR T-cell off the shelf, improving upon success that other people have already shown, little glimmers of clinical success. In two years, and I'll say the one year and a bit, If we had a check from today, everything can change timeline-wise, we could have an IND filed. And that if everything is aligned, right, another reason why you should partner with people instead of starting from scratch and thinking you should do everything. We're working with this academic institution that if everything did align, knock on wood, it wouldn't be a big delay from IND filing to treating a patient. And for Glioma patients, you know very quickly because the bar is so low, which is really unfortunate. So in two years, a little bit over, we could have clinical person-human data from a company and concept that only formed a little over a year ago. Which is wild with a capital spend of about probably a fifth what others have before. Not because they did things incorrectly. It's because we are learning and building upon and standing on the shoulders of others, for sure, to apply things in a different way. But in the meantime, a year could be a SEED round for us. You know, we're finishing a pre-SEED right now, being able to finally take it from not just validation. And we're pretty far ahead with this sort of clinical, being have clinical alignment now. But to have a SEED round to give us more funding to start really scaling up and showing what we can do. We not only have this research candidate, we have things in DC moving along with scaling and sequence lock. But also showing this mission of across the board that it's not just glioblastoma. It's so important for us not only to have an asset that's moving forward, but also show what we can do across the board. Whether it's gliomas, we have some concepts in brain mets. We're starting some work in a sarcoma I can't talk about yet. But being able to say, hey, KiraGen is this company that has the ability to go in these areas. We can partner off some things that we can't do on our own. We hopefully will have some maybe pharma pilots. It's another important source of capital we didn't talk about. Pharma needs innovation. So if you know that a pharma company might have an asset they need reviving, this is something that we're in early stage discussions on. Solid tumors is our kind of bread and butter, but liquid malignancies that are technically working now still are impacted by these solid tumor microenvironments. So we're very excited to at least have another year that we would show the world and really prove out the world more data about where we could go. I don't think it's going to say we're going to go in every direction. Where we could go, then in two years, using maybe a Series A to get through the clinic, we can have first human data that is helping people. And I mean, by that time, we really want to recreate this model. I know I'm going on long about this, but this model that we're starting with an academic institution, there are other institutions that have done really great work and have taken things from zero to one. We want to replicate that model. So if you're listening out there, it's a great call out or shout out. We are partner forward. And I think that was refreshing when I started hearing that, but to be external about it and say, we want to work with all these groups because they are the specialists that should take this proof of concept back into the clinic. And then we figure out the business along the way, whether or not that's going to be partnered with someone else or something we want to take into the company. So very excited next two years for us as a team. We might not have to grow too much because of this. So we're a team of six, which is pretty big for a small company of ours. But it's really building out our skill sets, making sure we're still taking in the tools as a team to grow where we need to grow, but not kind of take that same trajectory of those in the past. If we have people taking care of, say, the clinical execution for now, we can stay small, which creates optionality for us. And I say this loud and clear when people say, what's your exit? So, well, this is contrary. Take it or leave it. But I think that companies don't always need to be built to be bought. The companies that get bought are the ones that have just made sound business practices to set them up for optionality to be bought. So I'm not saying this is a pitch to be bought. I'm just saying to think about doing things like that, that at least give us the ability to start still change. Do we want to IPO if it works? Do we want to be sold? Do we want to go in other directions? You can't do that if you're taking in $300 million. It is like all or nothing. You got to go, you know. Space and back. So I'm very excited for the future and what it can hold and really want to encourage others that you can go against the grain. And while it's easy to say this now, and it might be hard during the moment, it'll make you better for it. Some people want to follow trends and some people's personalities want to do that and should, right? If it's timing's best, you get your money, you go in while the money is hot. Sometimes the best time to build is when people don't believe in you.  

Jon - 00:50:17: Having that optionality by maintaining your discipline as a company and running lean, it's more just like running efficiently is where you want to be. You never want your hand forced. That's it. You want to have options. Like that's the important thing. It's like. Let's not just like bet the farm and then burn the candle at both ends. Let's do it kind of like in stages and incrementally. And then when it's like, oh, this is to the moon. Let's put rocket fuel. Then you make that call. But I love that approach. It's really refreshing because I think, love my AI friends out there who are like running AI companies. And it's like. That's just pure rocket fuel, just like backing up the truck like right now.  

Aaron - 00:51:01: Yeah.  

Jon - 00:51:02: But again, I'm no expert, so I can't opine on that. But I like the discipline approach that you instill in your company and how you lead your company. It's really awesome to hear. And, you know. Traditional closing fashion, we have two questions. So first, I know you've already done a little bit. Are there any people you want to give a shout out who supported you along the way?  

Aaron - 00:51:22: Yeah, 100% my parents. So parents have been there from day one, had supported me, not only when I was a small town boy in education, but continuing to believe in me, right? You know, not the same when no one else did, but they've always been a constant presence in my life. And all of my Ms. Frizzle's, really important, like shout out teachers, teachers, teachers. And I will say Ms. Wathen, a librarian. So not just teaching STEM, but I had an amazing librarian when I was in elementary school that just like was a Ms. Frizzle of librarians. And, you know, some people along the way that saw more in us, like Ryan and I, before we did. So I like to like to call it T.A. Burrell was the chief finance officer at Beam that really saw something in me when I was asking about where I could go with my future and sort of saw me for me when I was really unsure, even before I went to HBS, right? Of knowing where I could, where I should go. And it was a big supporter of mine. I think those are pretty fundamental ones. And then at HBS, some of these, I know I've called them out and they are my Ms. Frizzle's, but raise the statue. It was really, really key. And some of these professors that were teaching us biotech models, that exposure has been really significant along the way. So everyone that's giving me a shot to do things a little differently. One more to call out. Wow. I can't believe I didn't call this out. Jen, what was Nwankwo? I can't, sorry, I can't remember her, knew her last name from 1910 Genetics. So she was an AI drug discovery company that gave me a shot before HBS and showed me what AI could be doing for small molecule discovery and business model. That was so key. Like people seeing something in others and giving people a shot when I didn't have my chops. I wasn't at HBS yet. I didn't have the credentials behind me. And then setting the stage for the future. And I now see her out and about. I always remember things that she taught me. And that is a fulfilling cycle. It's important to have people like that in your life because at some point in time, it is your job to give back. And it doesn't have to be when you're a billionaire and you're like donating to wherever it might be. Like my version of that is when people ask me for advice, like I was in your shoes. So I think it's being fortunate around these people that not only taught me, but gave me a chance. And I get to then give other people hopefully those chances to succeed in their own way.  

Jon - 00:54:01: Spot on. I like painted for it is so freaking important. Like no one does it alone. And like, those are the moments too, where you're just like, where you don't technically deserve it on paper and, but people are willing to go in, regardless, is a really beautiful thing. And I think it's like a special thing that should be cherished. And it's also, it's very rare, like being in the United States that we have that, but like I have family in the UK, I have family in Asia. It's not always like that. So it's like remembering that and be thankful that people are willing to pay it forward.  

Aaron - 00:54:38: Well, you know, and it comes in, I know you have one more question, but really quickly, it's important for me because, one, I didn't have visibility growing up. I was a gay kid, didn't know these science careers, but every step of the way, I have maybe gotten into different echelons of what I call privilege. I've always had white privilege, but I've been gay maybe, so I have some challenges. Now I'm in what you call the Ivory Tower. It is important for me to not think that my job is done bringing people to the table. And I think that's important to tell everybody is like, wherever you go in life, like you should try to bring, you should not try. You should be bringing people along the way with you because it is a success. Even if you're a manager, your report success is your success. My success is bringing more people to the table. You don't have to go to HBS to have access to these resources, right? You can do anything you put your mind to, and it's really important for people not to get comfortable and to make sure they're creating a space for others to do what you did or be able to ask questions.  

Jon - 00:55:42: Spot on. Proper spot on. And the last closing question is, if you could give any advice to your 21-year-old self, what would it be?  

Aaron - 00:55:50: This is hard. So 21 is when I came out. And there are a lot of fears until you have that moment of coming out, because I saw some people that weren't accepted by their families, actually, when they did. And then there are some that have full acceptance. And I think, if anything, it's a natural aversion of humans not to want to be hurt and to make mistakes and to fail, so to speak. But once you start doing it, you hopefully have the ability to build from it and overcome challenges. I would want to have stressed a little less and to know if someone if I could literally teleport back and have that conversation is to say, I know that this sounds corny because it is something we said so many times. But this person that I was then, that authenticity is a superpower. And it's that is definitely what I what I would say to the 21 year old. And it was told- It was said to me once at HBS that really solidified it. Someone in a shout out to Reza again. There was an example and, this is a long explanation, but we had a moment to get to know someone else in a class. And then the other person had to tell everyone what they thought that other partner superpower was. And someone told me it was my authenticity. And I'll never forget that. And I wish I could tell that to people, to myself and others, that being different and beating to the sound of a different drum is an advantage that you should lean into appropriately when you can. Because there's nothing like blending in that's going to make you different and be that person that makes a difference or makes someone smile. I think it's really important to know that being different is good.  

Jon - 00:57:38: Aaron, honestly, I could not think of a better place to round it out. That's like really, really critical. And I am a big believer in that as well. And I got to say, I didn't figure it out until recently. I thought I've had to fit a certain mold. Again, kind of what I was referencing, not as buttoned up as my colleagues or my peers, like, but that's okay. Yeah, that's totally okay. And I think I tried to fill other people's expectations or be what they expect to need to be. It was hard. It's very hard. And as soon as I kind of that switch flipped and I was like, screw it. And realize that it's actually kind of like a magnet. It's infectious.  

Aaron - 00:58:21: Yeah. People don't remember what you looked like, but they do remember how you made them feel. And that goes everywhere across the board. People want to do business with other people. Maybe they have good science to do business with. People want to see others and say, they made me feel great. Right? Like that's something I really aspire to and to create that for others. Like I'm comfortable who I am today and to make sure everyone that comes into the door at KiraGen. And I tried to do this in companies in the past, feel like they can be their authentic selves earlier than maybe they have in the past. If they want to be, it should be their choice. It's leaps and bounds. I'm not going to use the term that is a hot button term today, but like making people feel comfortable with who they are can be measured to business metrics and success, but you don't have to measure with business metrics to know that's just good practice. 

Jon - 00:59:15: Absolutely. Spot on. And Aaron, you've been so generous with your time. I've learned a ton and I like, seriously, like I, I pinch myself every time, like after I have conversations like this, I'm like, I'm so freaking lucky to be talking to folks like yourself. And I feel so privileged to be able to do this and to have the opportunity to do this. So Aaron, I'm cheering for you. And, you know, we're here to support y'all. And for real, like I wanted like the one year plan, the two year plan, seeing how this unfold. I'm fucking rooting for you guys, seriously. So thanks again. You've been so generous.  

Aaron - 00:59:55: Thank you so much thanks for having me.  

Jon - 00:59:57: Of course, and you know, next time in your, I'm in your neck of the woods, let's grab coffee. And you know maybe we can do it at IRL.  

Aaron - 01:00:04: Yeah, absolutely. I'd love to. Yeah, thanks again for having me.  

Jon - 01:00:06: Yeah. Thanks, Aaron.  

Outro - 01:00:09: That's all for this episode of The Biotech Startups Podcast . We hope you enjoyed our four-part series with Aaron Edwards. If you did, consider subscribing, leaving us a review, and sharing it with your friends. Be sure to join us for our next series, featuring Samir Khleif, founder, president, and CEO of Georgiamune, a biotech that is reprogramming immune responses. Disrupted immune homeostasis leads to disease. To address this challenge, Georgiamune is reprogramming immune signaling pathways to rebalance immune system components and restore health. They have designed targeted novel drugs to re-establish immune balance. Their groundbreaking strategies activate or downmodulate the immune system to fight cancer and autoimmune diseases. Samir is a pioneer in immunotherapy. A medical oncologist, immunologist, innovator, entrepreneur, and transformational healthcare executive. Before founding Georgiamune, he held academic and leadership roles, including chief of the NCI cancer vaccine section at NIH, where he led groundbreaking immuno-oncology and cancer vaccine trials. He was founding director and CEO at the King Hussein Cancer Center in Jordan and the director at Georgia Cancer Center in Augusta University. He is currently a biomedical scholar and professor at Georgetown University Medical School. Samir also served as special assistant to the FDA commissioner, leading the agency's critical path initiative for oncology. He sits on the boards of Ayala Pharmaceuticals and Emerald Biopharmaceuticals and has advised over 20 biotech and pharma companies. A global key opinion leader in immunology and immunotherapy, Samir served on national committees, including the Biden Cancer Initiative, SAB, as chair of the Immunotherapy Committee for NRG, and as a member of the NCI Cooperative Group. He advises the Parker Institute for Cancer Immunotherapy and is editor of three books, author of hundreds of peer-reviewed articles, and holds over 150 patents in immunology and immunotherapy. With deep expertise in immunotherapy, cancer vaccines, and oncology leadership, Samir offers rare perspective on translating scientific breakthroughs into real-world impact, making this a conversation you won't want to miss. The Biotech Startups Podcast is produced by Excedr. Don't want to miss an episode? Search for The Biotech Startups Podcast wherever you get your podcasts and click subscribe. Excedr provides research labs with equipment leases on founder-friendly terms to support paths to exceptional outcomes. To learn more, visit our website, www.excedr.com. On behalf of the team here at Excedr, thanks for listening. The Biotech Startups Podcast provides general insights into the life science sector through the experiences of its guests. The use of information on this podcast or materials linked from the podcast is at the user's own risk. The views expressed by the participants are their own and are not the views of Excedr or sponsors. No reference to any product, service or company in the podcast is an endorsement by Excedr or its guests.