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 part three, Örn unpacked the delivery challenge behind mRNA and the long preparation that made Moderna's rapid response possible. If you missed it, check out part three. In this final part, he turns to company building, staying lean, using AI and external partners carefully, and pursuing in vivo cell programming for difficult cancers.
Örn Almarsson - 00:00:56: Yeah. As someone said, it's an overnight success years in the making in that case. Right? And that, I think, is actually an important thing to talk about is that, you know, Moderna wasn't a well-known company in the beginning of 2020. You know? It was a company that some knew about, especially in biotech circles. But we had been quietly and consistently rapidly building capabilities in making the mRNAs we spoke about, making nanoparticles and chemistry associated with it, bioinformatics sequence optimizations, working with NIH, prototype vaccines, including those things we put in the clinic for flu.
But also importantly, they've been working on coronavirus vaccines, but not SARS-CoV-2, that some of the older things we knew about like SARS and MERS. And those were working in animals. We were just kind of learning that. And then finally, Moderna got into the game of doing something called personalized cancer vaccines, which basically uses the mRNA and bioinformatics to learn from sequencing of tumor tissue what are the mutations that seem to be driving for a given patient and then creating antigenic sequences. There's sequences that create antigenic proteins to train the immune system to recognize that and kill the cancer. And that's actually now really approaching a crescendo with Moderna and their melanoma combo. It's a cancer vaccine that hopefully will get approved this year. Amazing, amazing work.
I mentioned that last year because that's the stuff that allowed for the fast turnaround, you know, sequencing a genome of a virus now and then finding a way to train against that virus. That was an analogous solution, and it just sort of converged at the right time. And this is the story I tell because at the end of it all, people couldn't understand why we could respond so quickly, us and BioNTech, Pfizer. But it was because we've been training for years on all the things that you needed to be able to do. Very important training. Like, you watch Olympics maybe or some sport. You see this, wow, this kid. Wow. That's great, man. Won the gold. And you think, where did he come from? Well, you better believe that they've been training you since they were little kids, but first in town, then in state, and nationals. You just don't see them until it becomes really high visibility as Moderna rapidly became in 2020.
Jon Chee - 00:03:23: When I talk to my parents who are not scientists about this, via me, they kind of know a little bit about how long this stuff takes. But, like, to most ordinary people, they just don't know, like, how long it takes to get something like this to the point where it's ready. And this is always, for me, always just trying to foster the new generation and helping them get up and running because we need as much help as we can get as early as possible. That's why I think about also the capital stuff. Like, how do we fix this capital thing where we can get capital to the right people who are working on the right things? Because you kinda need all of these pieces together to get something like a Moderna. And then when the shit gets bad, we're ready. So you've built this groundbreaking technology where you're like, oh, I'm gonna spend the rest of my career at Moderna, or were you like, I need my next challenge? And, you know, obviously, COVID came. Talk a little bit about that time period and how you're thinking about what was your next chapter.
Örn Almarsson - 00:04:25: Right. COVID came. Once again, I wasn't planning my next move. I had spent almost seven years at Moderna, and it was heavy lifting. And, really, I was approached by an old Merck colleague, Trish Hurter, who had a proposition on a technology that I think is super cool and is ultra-long-acting oral delivery. And that's being developed now for basically birth control, especially in developing countries where you can't be giving medicines multiple times. So that's really cool. And I got a chance to be the chief technology officer of this company called Lyndra. And I took that on. It was a bit back to the future for me going back into sort of this controlled release and oral and small molecules for the most part. But I kept thinking about RNA, and I kept thinking, oh my, this is so cool. What's gonna happen in the future? I decided at some point, I'm gonna do this myself. I'm gonna try to find my own path, and that's why I'm here.
Jon Chee - 00:05:25: Very cool. You've had this culmination of experience, and now you're like, okay. I'm going to do this on my own. I'm gonna start this company. Talk a little bit about the very beginning of actually getting this started and stood up, and talk a bit about the North Star that you set for the company and the technology that you guys are developing.
Örn Almarsson - 00:05:45: Right. So first of all, Axyleth is developing in vivo cell reprogramming. So it's in vivo CAR T for solid tumor, which is not yet cracked, and it's supposed to get around this from ex vivo, which is a very important twentieth-century revolution in medicine, but not scalable. And now we have a scalable solution. We're proceeding with the first indication, but we're mindful. We have a very modular, cool lipid nanoparticle binder to different cell types and then cargos to deliver and do cell reprogramming. You can present new proteins like a CAR, chimeric antigen receptor, on a specific type of cell to either kill a cancer or deplete these cells or whatever.
And it's an unbelievable opportunity, and we feel we have this combination of best-in-class lipids and cargo modularity design that really is important. And so we are taking this challenge on as this group of five, so it's a small company. We got our seed financing about a year ago. And, fortunately, I feel, operating in a time when seed financing is getting better, and that's making me optimistic. And we do a lot of this work virtually because I believe in using the networks again, CDMOs, and being very capital efficient. So this is important. And so we started the company on lipids, actually, and that's because I had this long history with lipids. And it wasn't just Moderna, but it was longer than that as I think I told you.
Jon Chee - 00:07:15: You're like, undergrad?
Örn Almarsson - 00:07:16: Yeah. Yeah. And I have this idea. The very first idea of a company was on a trip to Iceland right before COVID. I was looking at an anti-inflammatory lipid from nature called astaxanthin. We did some work on that. That was the initial kind of start. Now we are really into ionizable lipids and surface lipids and binders to build ultimately a modular toolkit to make in vivo cell reprogramming products.
And that is a future. I think it's unbelievably bright. It's gonna help so many patients, both with autoimmune disease, but in our case, we wanna really treat cancers where the five-year survival rates in some of the indications are ten, twenty percent. Pancreatic cancer, hepatocellular cancer. These are really difficult, and the things that have come to the fore over the last few years are helping, but we gotta do way more. There's a lot of room to improve. And these technologies, I feel, are really gonna come in strong.
And I think back to something you said about the speed of development, I think there are signs that we can do this faster. Not only are we getting wiser with respect to how to use the technology, we have AI to help us with sequences and all kinds of modeling that really is incredibly important, and it's democratizing it in a certain way. And then we have an FDA now that's starting to worry more about, even despite all the changes in our peoples, they're starting to think more about how do we support drug development better. I mean, there's really important signs along the way that say, you know, we've always been partnering with FDA, but I think we're gonna be partnering even more. And there's gonna be an opportunity to register compounds on a more of a rolling basis as opposed to requiring multiple studies for a registration because patients are waiting.
Jon Chee - 00:09:08: Yep. Absolutely. And you're talking about building this company capital efficiently and also kind of primarily virtual. Can you talk a little bit about that strategy and how you're thinking about company building from that perspective? Like, what aspects are you focusing on to stay efficient? And you mentioned CDMOs and CROs. You know, if someone out there is just listening in, how can they stay efficient and nimble to be able to make those pivots?
Örn Almarsson - 00:09:36: There's a couple elements of strategy. One of them is in this moment, you gotta have a hypothesis for how you're gonna use your combination of technologies which makes you different and better to treat something. And so we've actually opted to go after hepatocellular cancer with a specific CAR. And then that is a program we designed after I hired a key person who's in the San Francisco area, actually, Danny. He's really come in strong, and we're building that with companies around the world who are helping us do this work.
And it's about using information, and AI is a big part of this, and mining information about patients and responses. You can find stuff in the literature. Sometimes you just have to dig, and then you learn as quickly as possible. The models of the last couple years are really changing the way I think about scaling a company in terms of leveraging the AI and being AI-informed. And we, for example, we took a stab at modeling lipid nanoparticle performance, which not many people are doing because the language models are really great for repeat sequences, letters, and words like proteins and nucleic acids. But for these disparate lipids and combinations, it's not as easy.
And so I found that models were not really very predictive, and I had just built this library and acquired the two in part. And we had a lot of data, and we built models with enough diversity and enough consistently curated data to start to improve predictions over what was in the literature. And so we use that to a point to inform our decisions on lipid selection, but I'm gonna be fully transparent. It takes more to make these predictions better for the very strange system that is lipid nanoparticles. And so AI certainly is helping us there. But overall, strategically, stay small and hire extremely well. Use the network, and use the tools that are emerging over the last couple years in such a strong way. There's no turning back.
Jon Chee - 00:11:45: Absolutely. And I guess when it comes to selecting a partner to help you develop something, what do you look for in the ideal partner? Like, I'm going to imagine if you're working with a partner, they're gonna specialize in some or do you prefer to go to one partner who can do a lot?
Örn Almarsson - 00:12:01: The notion of a full-service, one-stop shop is great, but I think it's sometimes, at least in part, a concession. You're giving up something. So I think it's better to work with a couple more and manage that, but then be able to oversee that supply chain, for lack of a better word, so you integrate it. Then the other thing is that there are different things you have to do, mRNA or lipids or nanoparticles. Not everybody does all of those things yet. I mean, a couple do, but I choose to do it sort of in different places.
Jon Chee - 00:12:35: Cool. And when it comes to your pipeline development, is it all internally developed? Do you guys do external collaborations at all, or is it just everything in-house?
Örn Almarsson - 00:12:44: Our drug product comes together from things that we've invented, so we're not reliant on anyone else. But that said, you know, in the early days, like last year, we were working with companies, just Copel Farm and Biotech, that I have connections in, and we did some work together to demonstrate delivery of different types of cargos to give them some idea of what we had and give us some idea of what the breadth of capability could be for different types of payloads. And I think that's been very helpful. We don't yet have an announced collaboration, but it's part of the model as with many biotechs. You know? You work on your program, but then if there's something you can do a partnership or collaboration on, I'm certainly open there. I'm used to doing that on both sides, right, from the big company and the small here.
Jon Chee - 00:13:38: Absolutely. And the last piece of being able to stay efficient and lean and nimble about just utilizing the AI tools that are available to us right now, even in just the past three months, I'm just like, holy moly. Like, it is incredible. And, like, just to geek out, you know, we're not dealing with scientific data like that you guys are, but we've been virtual and remote-first since the very beginning. And right now, San Francisco is very in-office. Like, a lot of places are just five days no matter what. And we're still staying remote. We have teammates all over the country.
But something that I did notice about being virtual is that you got to be good at documentation and writing. So how else are you gonna communicate? If someone's like, "How do I do this thing?" Yeah, you can do it over a call and try to teach someone over a call, or you can write it, and then it can be referenced later. And same with, you know, now if a call is like, we're talking about some important stuff here, we'll just record it. Someone can just reference it almost like an internal webinar. And so we actually just found this tool where all of our fifteen years of written SOPs, call recordings, data, just everything that we've gathered, it basically stitches it together into this corpus of company brain. And so what's cool about that is that now as you hire, rather than having an onboarding that might be, whatever, three months.
Örn Almarsson - 00:15:08: A week?
Jon Chee - 00:15:08: Yeah. It's like a week. We joke internally. It's kind of like in the movie The Matrix where they just plug into Keanu Reeves' head, just like, "I know kung fu." Like, you're just plugged in. Like, I know kung fu now. And that's what we're seeing. Like, the time to just be able to ramp up really quickly with the use of these tools is possible now. Like, it can just synthesize hundreds of pages of know-how and just serve it up to someone at their fingertips is so cool.
And it's, for me, it's really fun to be building this way again. And I used to think staying small and remote-first and virtual is kind of like a disadvantage to the big dogs who are like, "We have an unlimited purse to just do whatever. We can throw money and people at this infinity," but now it's like, oh, we can do what the big dogs are doing. Like, this is possible now with everything that's the advent of everything, the technology that we have. So I'd love to hear that you guys are also utilizing it, and it's enabling you guys to really just move quick and stay lean and efficient as you guys are blazing this trail. So as you're looking one year, two years out, what's in store for you guys, and what's in store for you?
Örn Almarsson - 00:16:21: Yeah. I mean, we want and need to start in the clinic within the next two years, and that'll require certain fractional hires, people that we definitely need to have on board. The lab is a definite possibility for us, and that's just because, you know, now that we've started to de-risk our technology, we'd like to learn about it, these important crown jewels, on our own time and dime in our own place. So that's in the future, and I'll talk to you about that separately.
But the other thing is I do lean into scaling with AI and the natives. You know? They're there. I mean, people on my team are, they're helping me as an older generation guy, and my co-founder John is a similar age as me. We're trying to really lean into it because it is just, there's no turning back, and there's really great ways to use it. I loved your example from earlier, and it's really that sort of symbiosis of AI with great people who know how to use AI and can get really good at it. And I will say 2026, it's just been an awakening. It's just hit me so hard in a good way.
Jon Chee - 00:17:29: Yep. And I love it too because all the experience that you have had over every single company, big, small, going in every direction, that only makes you and your organization that much more differentiated because you have this knowledge that you can now impart to everybody. Like, your knowledge can be everyone's knowledge, which is super awesome. It's a really exciting time for building, which is really, really cool. And I'm rooting for you guys. Like, getting into the clinic, you know, in the next year or two, the exciting stuff, you know, it's hard stuff, but exciting stuff, super critical. And you've been so generous with your time, and I've had a lot of fun. I love hearing, well, one, that you had to go on witness protection. That part just—
Örn Almarsson - 00:18:12: Academic witness protection.
Jon Chee - 00:18:14: Yeah. Yeah.
Örn Almarsson - 00:18:14: I'm geeking out in the lab as opposed to rocking on stage.
Jon Chee - 00:18:18: Yeah. And no one knows. Just no one knows. And you're just like, this is actually nice. Like, I can actually live a normal life.
Örn Almarsson - 00:18:26: I've evolved, you could say. And I keep evolving. I think I view that life as that series of evolutions and sometimes revolutions. You know?
Jon Chee - 00:18:34: Yeah. Absolutely. We have two closing questions here. So first question would be, one, would you like to give any shout-outs to anyone who supported you along the way? I know you've mentioned folks already, but if there's anyone else.
Örn Almarsson - 00:18:46: Yeah. I know that. I mean, great mentors, Elliot Ehrich, Colin Gardner. I'm missing a few of those three. If I had to pick three that were just absolutely fundamental to who I am as a scientist, as a professional. You know, my wife, I mean, we have been on a journey. And today is actually the thirty-eighth dating anniversary, so I did get flowers.
Jon Chee - 00:19:07: Yeah. Congrats. Congrats.
Örn Almarsson - 00:19:09: Yeah. Thank you. Yeah. That's great. I mean, you need to have the support of people along the way, which I've been fortunate. And sometimes I feel emotional about that because it's just, the things they did for you, they didn't have to do that, but they chose to do it. They saw something, and they chose to do it. And I am not taking that for granted, so I tried to do this heaven. And I stay attached with my mentors, which is something else I tell people. Please don't forget your mentors because they wanna hear from you. And so those are the things. I wish I could go longer, but I'm not because it's—
Jon Chee - 00:19:40: It'd be endless.
Örn Almarsson - 00:19:41: It is a long list. Yeah.
Jon Chee - 00:19:43: Yeah. It would be endless. And last question is, what's the best piece of advice someone else has given you?
Örn Almarsson - 00:19:48: I come back to Colin Gardner. I pay homage to him a lot, and he said to me when he joined Transform and, you know, keep in mind, he was three or four levels above me at Merck. Okay? And then he comes to Transform, and he's the CSO. And he has me and a couple of people reporting to him. And he says to us, "I'm way more experienced than you at this a long time, and I could easily go out and hire middle management to be in between us. But I'm not gonna do that, and instead, I'm gonna expect you to catch up." And it's profound. Right? It's like saying, here's a coat. It's big for you, but you work out, you do all those things, you grow up quickly, you're gonna look great. And that's really, I think, the most profound thing for me because I try to do the same for people. You do have to take charge of your own development. But when you get an opening, like an offer or advice like that, just catch up. That is super profound.
Jon Chee - 00:20:44: I've never heard it put that way, but that's awesome. Like, that's freaking awesome. And, like, I think right now, especially with all the new technological developments that we're seeing right now, giving the people and your team the chance to just to catch up, like, believing their ability to do it, is such a gift and also just a great way to inspire. It's just like—
Örn Almarsson - 00:21:08: For me, it's like legacy making in a way, and what he did for me and us at that time was he created running room, and he created expectations, high expectations, no doubt, but also some safety to fail or to learn quickly and fail. And I think that's kind of something I wanna adopt. I kind of summed it up in a way that I think is also really something that's come to me recently is that if I can sum up my reason to be on this Earth, it's to be a catalyst. And so it has multiple layers of meaning for me because I studied catalysts, enzymes, and so on as a graduate student in chemistry, and the catalyst makes something happen faster by bringing things together and lowering the activation energy for it. And therefore, things actually happen that otherwise would take way too long. So that's one thing.
The other thing is a catalyst, this is a key. Catalyst is not consumed in the reaction. It gets to do it again and again. That's just how I feel. I feel like that's another sort of insight that I've had about myself, which I'm really happy to be able to share that with you here today.
Jon Chee - 00:22:14: I love that. Thank you so much. Like, this has been really, really fun, and I've learned a lot. Thank you for sharing your story. You know, the next time I'm in the area, I'll give you a shout. And then next time you're in the Bay Area, I'd love to take you to coffee. Maybe we'll phone Derek when he's not in the Alberta wilderness.
Örn Almarsson - 00:22:31: Exactly. Thank you for this, Jon. I really appreciate the opportunity to tell a story here. I'm really excited about your work in the podcast, and I appreciate that.
Jon Chee - 00:22:39: Of course. Thank you for taking the time, and I'll see you again soon.
Outro - 00:22:44: Across academia, pharma, startups, and RNA delivery, Örn keeps returning to the same role, bringing the right people and ideas together, lowering the barriers, and making progress happen faster. His definition of a catalyst is both scientific and personal because the best leaders help others move without being consumed by the reaction. Enjoyed the series? Leave a review and share it with a friend. Thanks for listening.
Join us in our next series featuring Leslie Loveless, CEO and managing partner of Slone Partners, an executive search and talent strategy firm serving life sciences and healthcare organizations. Leslie joined Slone Partners in 2007, became COO in 2014, and took on the CEO role in 2016. Before Slone Partners, she worked in healthcare sales and sales training at Quest Diagnostics and AmeriPath after beginning her career as an educator. Her path from teaching to healthcare sales to leading a life sciences search firm makes this an episode 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.
