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.
Örn Almarsson is the co-founder and Chief Executive Officer of Axyleth, a company developing RNA medicines for cancer and autoimmune disease. Its AXL platform is a lipid nanoparticle delivery system for RNA, and its ANNA model uses AI to help design new lipids. For listeners, the central question is simple: How do you get a powerful medicine to the right cells in the right form without losing it along the way?
Örn's career has followed that problem from multiple angles. He trained in chemistry at the University of Iceland, earned a PhD in bioorganic chemistry at UC Santa Barbara, completed postdoctoral work at MIT, and held research leadership roles at Merck before moving through Transform Pharmaceuticals, Alkermes, Lyndra Therapeutics, and Moderna. The through line is practical science: understand the mechanism, build what's missing, and keep moving towards something that can help patients. From Iceland and Denmark to major pharmaceutical labs, startups, and RNA delivery, electric guitar, a chemistry lab, and a mentor who helped turn early curiosity about lipids into a career in bioorganic chemistry. Without further ado, let's dive into part one of our conversation with Örn Almarsson.
Jon Chee - 00:02:09: Örn, so good to see you again. Thanks for coming on the podcast.
Örn Almarsson - 00:02:12: Thank you for having me.
Jon Chee - 00:02:13: I know it's been a while, but, yeah, I've been really looking forward to this, and I love how such a small world it is when it comes to science. You had mentioned that your friend, Derek, had come on the podcast years ago. So really excited for you to be here and to give me the time to have this conversation with you. In traditional opening fashion for the podcast, we always want to go all the way back and learn about what inspired you to get into science, get into business, and really learn about the formative moments during your adolescence. So take us all the way back. What was it like growing up?
Örn Almarsson - 00:02:44: Yeah. So I'm born and raised in Iceland for the most part. So I'm Icelandic by birth. I'm a US citizen now, but we'll get to that. And I thought it was great to grow up in Iceland. It's a place that is a little out of the way, but that means that people who grow up there want to go out and kind of explore the world, and we are known explorers. And then I had part of my upbringing in Denmark, and that was because of a job that my father had. And so that was in my teenage years. I loved Denmark. I loved living in Copenhagen, and I was in an international school, learned English there, and was obviously conversant in Danish. I had a little bit of Danish family and just had the best time.
But then we moved back to Iceland. Luckily, I bought my first electric guitar in Copenhagen, and I was playing in a little band there. And then in high school and college, I played more seriously, but it was such a great experience. And I always thought, I'll move from Iceland again. It'll probably get too small for me, but it was a great place to grow up, and I still go there a lot. I have family and parents there, so it's a nice place to grow up.
Jon Chee - 00:03:47: Were your parents both musicians, or was this a hobby that you picked up on your own?
Örn Almarsson - 00:03:51: No. Neither parent, actually. And I'm the only one of my siblings that did something and played. My aunt was actually a performer, though. She was wonderful. She could yodel—
Jon Chee - 00:03:59: Sweet.
Örn Almarsson - 00:04:00: —and sang in a trio. She was fantastic. I miss her.
Jon Chee - 00:04:03: That's amazing. Yeah. It was funny. When I was growing up, I was like, "Yeah. I'm going to give guitar a shot." And I was like, "Oh, I'm awful." I was like, I'm better at listening than actually producing music and playing an instrument. When you were a teenager, were you like, "Oh, I might actually become a full-time musician, spend my career playing music," or was this something that in college and in high school, you took a little bit more seriously, but were you like, "I want to be a star?"
Örn Almarsson - 00:04:31: Actually, it's an interesting one. There was a tension there at the time because I was getting interested in science in my teenage years, and I thought I'd be an engineer and use science and build things and see how they work and see how they fall apart and all that stuff. But I was playing music on the side. My mom used to complain. Actually, she complained to the ladies in the neighborhood. Like, he comes home, throws his school bag down, and picks up the guitar and runs, and I would hear it secondhand. The boys would be saying, "Hey. Your mom is worried about you." I was like, "I don't know."
But it was all an interesting tension and a balance. I did play fairly seriously. I was involved with guys who ended up going to Berklee School of Music and doing the thing, and they're jazz guys that I love the music. I listen a lot like you, and I play a little, and I mostly play for my grandsons now. They're the only interested parties here. But it's a great thing to have, and there are some things you can draw up from music to real life, and especially when you play together with people. How do you work together and solve things and improvise and make something beautiful?
Jon Chee - 00:05:38: What was the music scene like in Iceland and Denmark?
Örn Almarsson - 00:05:41: Well, it was the late seventies, early eighties, so it was like rock and roll and bands like The Police and The Jam and Pretenders and stuff like that. And I loved that stuff. And then the bands I played in were a little bit more rock and roll, Rolling Stones, things like that. And we recorded original music as well.
Jon Chee - 00:06:00: Cool. Very cool. Yeah. I was going to say, I really should be doing it more now being based in San Francisco. There's always so many great shows coming. It's nice to be in the Bay Area where people are always swinging by. And I still enjoy live music very much so, but especially growing up, went to a lot more shows. I may have told the story, but I had a punk rock stint.
Örn Almarsson - 00:06:22: Oh, okay. Yeah.
Jon Chee - 00:06:24: I think I might have a little bit of a rebellious nature. And I guess running a company and startup, it's not a normal thing to do.
Örn Almarsson - 00:06:31: You have to be contrarian.
Jon Chee - 00:06:34: Yeah. Also, I think Jensen Huang of NVIDIA talks about it. If you just know beforehand a priori what it takes to do this thing, you just think no sane person would do this.
Örn Almarsson - 00:06:44: One of the bands I didn't mention was The Clash, and I saw them in Copenhagen. I thought that was so cool. But, you know, now I listen to it. It's like, this is very grungy, and it's a part of my life, and I was probably a bit angry and frustrated then.
Jon Chee - 00:06:58: For sure. Yeah. You know, some family friends who are investors now in their career, they described when they were at UChicago and they saw the Ramones in just a dive bar. I was like, "Oh my god, at a dive bar," and literally just busted open the doors and you could just feel swept by sound, just in this small, dingy Chicago dive bar, which is like, man, that would have been so rad to actually be able to experience that. So you're playing in bands. Did you major in music in high school and college?
Örn Almarsson - 00:07:38: No. I didn't do that. I was more like a science major, but the thing is that I studied music since I was about seven. I played classical guitar first, and then I took some jazz lessons from a guy that had just moved back to Iceland. I'm still in touch with that guy, and I support his music. I do love that, but it wasn't a major or any kind of really formal thing for me.
Jon Chee - 00:07:59: Very cool. And how did you get into science? Was that also a thing where you independently found the spark, or was that something in the house growing up? How do you get into it?
Örn Almarsson - 00:08:09: No. I think that was more around me. So my father and my sister are pharmacists, and they work in pharmaceutical, but more in other areas than actually the drug itself. And I really, obviously, imbibed that, and there was a lot of talk about different things. And there was so much going on in pharmaceuticals over the last forty, fifty years, and I'm listening and learning. But I'm also thinking, I'm really more curious about the intel inside. Like, what is that stuff? As opposed to how do we prescribe that, and is this tolerated, and the clinical aspects, which are very important. But I got so into the science and the engineering of that, and that sort of started driving me as I was going through college.
Jon Chee - 00:08:51: Very cool. And when you were selecting college, where was your head at? Was it a similar thing where you're like, I need to get farther away from home? What was the college selection process for you?
Örn Almarsson - 00:09:02: It's relatively simple because although I thought about going back to Denmark and doing college there, I actually ended up at the University of Iceland. The education system is a little bit different, so it's not exactly in the US. But the short version being, I decided I'll go study chemistry at the University of Iceland with the idea of finishing up as a chemical engineer either in Denmark or in Sweden, in Gothenburg. There were these options.
And I should point out here that University of Iceland back in the day when I was going to it, it was an undergrad institution mostly. The only graduate studies were in Icelandic history and language. You know? The things you couldn't find anywhere else. But what was great about that, though, for me, and I feel lucky, is that the university was very focused on its undergrad education. They had some research opportunities, and I was a beneficiary in that, but they definitely focused on having a very strong European-focused rigorous chemistry program. And then you have to go elsewhere if you wanted to do that. And I was one of those people. There were several people around me that were going to go to grad school, and I decided to do that too.
Jon Chee - 00:10:10: Very cool. It's interesting that you bring up the dynamic of when a school has an undergraduate and a graduate program. I went to Berkeley. Undergraduates are kind of like an afterthought.
Örn Almarsson - 00:10:22: Unfortunately. Yeah.
Jon Chee - 00:10:23: Yeah. You're just like an afterthought. You're kind of like a factory, just going in and out, in and out. Whereas, you know, obviously, they hyper-focus on the grad programs. So it's cool to hear that there was a flip, whereas it's like, no, we're hyper-focused on the undergraduate experience. Were there any courses or professors that perhaps really made an impact on you or maybe took you under their wing?
Örn Almarsson - 00:10:45: Yeah. Definitely. I mean, I'll mention one of them. He recently retired, and it's Haraldsson. Haraldsson came back to Iceland when I was in my second year in university in chemistry, and he's an organic chemist who came from Oxford, was in a prestigious lab there, and came to Iceland to teach organic and also do research. And so luckily for me, after my second year, I took a class with him, and then I got an internship in his lab. And I couldn't believe how fun that was.
There was a couple of us who got that opportunity, and it was lipids, by the way. You'll hear more about lipids, but I was doing tailored lipid synthesis with enzymes involved and organic solvents, and it was just really exciting. And I think at that moment, I knew I was kind of going to go for it and go to grad school and do some more research and things. And Haraldsson was a catalyst in that, and I really appreciated that. I'm still in touch with him.
Jon Chee - 00:11:41: I love that. I'm always curious about how people get their first lab experience. And as I'm hearing people's experiences and securing that first lab spot, it's always almost serendipitous in how people get involved. Like, even at Berkeley, it's almost like an apprenticeship model. It's not overly formulaic or procedural. You're just like, "I was in touch with this professor," or "I have a friend in the lab who thinks that you'll have a good time here," and then you ultimately get apprenticed in a given lab. And it sounds like they have an outsized impact on your journey.
Örn Almarsson - 00:12:16: Definitely. And what's interesting too, another thread in that was that he was able to get funding from two European companies that were using enzymes to do stuff, and one of them was Novo at the time. They are now called Novozymes because they've been spun out. But I had a chance to work with a couple of people there in Copenhagen for a couple of weeks just because the project had a tricky thing that I needed to tech transfer. That's kind of a first exposure to industry for me.
I'm now, I think, a third-year student or something. I get to continue my research along with classes, and I'm thinking, I'm doing this work with industry people. I get to see, how do you think about problems? And I think that was very formative as well. So that first experience in the lab with the project was just amazing.
Jon Chee - 00:13:06: That's incredible. Again, just what are the chances? You see, one, lipids. Two, Novo. I didn't even know what any type of research was like outside of academia for such a long time. I was just like, "I don't know, it's just academic research. This is it." To get that exposure set so early on is incredible. I guess, a question for you, what excited you about seeing what industry was like compared to your experience being in an academic laboratory?
Örn Almarsson - 00:13:33: Yeah. I think it was just focused on, we're making something that's supposed to get commercialized and help people and systems get some product. And I think that focus started to generate some interest because, I mean, academic research—and I did do academic research as a PhD and a postdoc—it's definitely a foundation and a contribution you can make at the same time, but I never really saw myself being academic full-on. I kind of have an academic side to me, but I really want to be practical and applied. And that's what I saw from these people, the kind of questions they asked, and it was about timelines. And perfect is the enemy of good. How do we get there? Right?
Jon Chee - 00:14:14: Yep. Absolutely. And so now you're like, "Okay, I have my sights on grad school." How did you think about that? How did you select what grad program and what lab to go to?
Örn Almarsson - 00:14:24: So my thinking was evolving. I think I mentioned earlier that I was thinking about going to college or university and initially do my undergrad in Scandinavia. So I kind of started there. There was a group of us who were—people had gone before us, and we were thinking about going. And one of my best buddies actually, who I'm still in touch with, went to Berkeley. He was in chemistry there. And so I was thinking about initially Scandinavia, UK, where my professor friend, Haraldsson, went.
But then I thought, the US sounds good, actually. And, you know, they have these—you can do TA and RA. That became interesting. And then I thought, as long as I'm going to the US, I might as well go all the way across. And I ended up in Santa Barbara with UC Santa Barbara, which was a fabulous place to live, not a place to make a living if you're a scientist. But—
Jon Chee - 00:15:11: It's beautiful out there. Gorgeous.
Örn Almarsson - 00:15:14: Absolutely gorgeous.
Jon Chee - 00:15:16: It's amazing. A family friend did the same. He was not in Iceland, but he grew up in the Cambridge area. He was just like, "I'm getting out of this winter. I'm going to Santa Barbara." And it was just like, "Oh, yeah." He's just like, "Everyone's generally happy here."
Örn Almarsson - 00:15:31: Yeah. I had a great time. I really did have a great time, and I had a great professor there. I still am in touch with his widow because she's a professor of chemistry as well, and I just love that place.
Jon Chee - 00:15:43: Was it a specific lab that you had your sights on, or were you like, "I'm going to get to Santa Barbara and figure it out?"
Örn Almarsson - 00:15:49: I targeted a couple. It wasn't a singular one. There were two professors in particular that I was looking at. Unfortunately, one of them, the guy that I really wanted to work with, Tom Bruice, he was available, but I did get the advice when I got there. He was called TC. Never to his face, but just, "TC is tough, man. He's a World War II veteran. He's just really old school, and he's rough on his postdocs and super demanding. I don't know." They were people trying to tell me not to do this.
But I got on with him so well. I mean, he was old enough to be my grandfather, but he was so supportive. I mean, he just kind of had this way about caring about it, but he was tough too. He could occasionally have a slight temper, but I'm so appreciative for him. He would have been 100 last year, and obviously, he passed away in his early nineties, and we celebrate him. He was one of the founding chemists behind something called bioorganic chemistry, and that became my field. This is the application of organic chemistry and physical chemistry to mechanisms in biology, and that's kind of what I'm interested in.
Jon Chee - 00:16:57: Really cool. I feel like I gravitate to mentors like that as well. It's almost like a tough love type mentorship. It's like they get fiery about it because they care.
Örn Almarsson - 00:17:07: Yeah. Absolutely. And you could tell he cared. It was about really solving important problems. Another thing he taught me was instead of diving into something and spending your entire career on that, look at a problem that is maybe not being solved well or needs some orthogonal or bioorganic thinking and take it off and be fearless about learning that. And he did that. He did that through his career, and I caught sort of one wave of that as a grad student there. And I thought it was just an amazing way to go, and I sort of applied that thinking to my own life and career.
Jon Chee - 00:17:43: I love that. How big was this lab? Was it like a larger one, smaller one? What was working in that lab like?
Örn Almarsson - 00:17:49: Oh, it was about 20-ish, give or take. Most of them were postdocs from all over, and there was about maybe, at any given time, four or five grad students. We were the minority, and we were given a little bit more slack than the postdocs. But his point was you hire somebody like that and you pay them more than a grad student, and they better well hit the ground running. So I did see some early departures there, and it was a bit intimidating.
But I got on with them really very well. I mean, for the most part. I mean, I think anyone who's ever been a grad student will tell you that the relationship generates tension, especially towards the end when you think you're ready to leave and he doesn't want you to leave, and that's the tension. But we worked it out. We worked it out very well. And the hardest part was sitting in his office editing manuscripts when he was a smoker, because he smoked. He smoked a lot, and his office was small, and he didn't open the windows. And I was sitting there. But I survived that, and he had to stop smoking because he got pneumonia and got very sick. And we were worried about him because he wasn't a young guy at that point, but he came back from that strong and not smoking. Thank God.
Jon Chee - 00:18:58: Good for him. Good for him.
Örn Almarsson - 00:18:59: Lived to 93. So.
Jon Chee - 00:19:01: That's a badass.
Örn Almarsson - 00:19:02: He was. He really was.
Jon Chee - 00:19:05: Were you playing music all through your grad school as well?
Örn Almarsson - 00:19:07: Not as much. No. Because now—and I'll tell you the story. I call it, it's like being in an academic witness protection program. You know? I left Iceland when we had done a lot, and we were well known, and we were world famous in Iceland, actually. Yeah. Yeah. But we were also a little bit controversial because there was all kinds of what would now definitely not be very PC.
Jon Chee - 00:19:28: Yeah. Yeah.
Örn Almarsson - 00:19:29: There was even cross-dressing involved.
Jon Chee - 00:19:31: Okay. Cool. Cool.
Örn Almarsson - 00:19:33: So I had to get out of there, and I had to leave the continent of Europe and go to the US. And so I didn't really play much.
Jon Chee - 00:19:41: You're under WitSec.
Örn Almarsson - 00:19:42: And, fortunately, the Internet didn't exist. So, yeah, people couldn't Google me. You know?
Jon Chee - 00:19:47: Yeah. Yeah. Yeah. I was going to say, like, nowadays, everything is just chronicled on the Internet. I'm so grateful. Just like, "Oh, no. I'm glad there's no trace of this."
Örn Almarsson - 00:19:58: Right. I sometimes say that around the time when the world discovered Moderna, which we'll get to later, Moderna discovered me because some people in my group found the videos.
Jon Chee - 00:20:08: Oh, they did?
Örn Almarsson - 00:20:09: Yeah. And then they started showing them randomly on screens in the company, and I was like, "Do I have to find another continent now?"
Jon Chee - 00:20:16: Yeah. Gotta move again. Man, that's so funny. So now you're, you know, you're in witness protection. You're in the lab. You mentioned as you're kind of approaching the end of your grad school, "I'm ready to spread my wings a little bit." At that point, you know, it sounded like you're pretty firmly, "I'm not going to just go and be a professor." You're starting to think about industry, I'm assuming. Did you know what was next? How did you kind of go on to your next venture?
Örn Almarsson - 00:20:41: So, yes, I was in Santa Barbara. I got married in the meantime, and I have two kids already. I do everything at once. And my wife is Icelandic also. Fortunately for me, she is just my partner for thirty-six years now who, you know, we've done everything, traveled everywhere and stuff.
And I was thinking about going back east to begin with. I said, "You know, I think California is great, but I kind of want to be somewhere where I'm maybe physically and culturally a little closer to my background and close to my folks." And so we started looking at that. And I did end up looking at a couple of jobs, but there weren't that many at the time. There was a healthcare freeze due to healthcare reform by Hillary Clinton and people like that. Some listeners may remember that.
And I decided, oh, I had an opportunity to do a postdoc at MIT, and that was a great year. You know, we moved to Cambridge, and I worked for another very memorable mentor, Alex Klibanov, in chemistry there. And that was an experience that actually really ended up helping me because the only time I really had to look for an industry job was when I finished my postdoc, and I got a job fortunately at Merck. And what they say is Merck, at the time anyway, loved to hire MIT engineers and Harvard medical people. You know, that was Harvard medics, MIT engineers. And so I'm an MIT sort of chemist, but I only did a postdoc there. But it was a great year. I accomplished some things. I learned a lot. I mean, Alex taught me a lot about—it was a nice contrast to the old-school thinking of Tom Bruice and sort of a new way of kind of communicating and pursuing the science, and I really enjoyed that.
Jon Chee - 00:22:22: How would you compare being a PhD student with being a postdoc and maybe contrasting the two institutions as well?
Örn Almarsson - 00:22:30: Yeah. I mean, there's a definite requirement, I think, when a postdoc is hired, it's assumed that person has a strong foundation. Can they quickly use their frameworks to get at a problem because they're only there for a short time, usually one or two years. And so I felt that pressure having especially seen what happened sometimes to postdocs in my previous life. So I made a goal of it, and I was lucky. I had good support, and I also got to know some great people at MIT. And just as I felt a little bit bad for the postdocs at Santa Barbara, I felt a little bad for the grad students at MIT, you know, because they were under a lot of pressure.
Jon Chee - 00:23:05: Perfect for you. A nice switch.
Örn Almarsson - 00:23:07: It's a nice switch.
Jon Chee - 00:23:07: Yeah. A good switch. That's excellent. Was there an active recruiting program? Was it a very formal thing, or was it more informal when it came to Merck and finding that opportunity? Because I know at Berkeley, they have these career fairs where there's these recruiting cycles. Was it the same at MIT?
Örn Almarsson - 00:23:25: Yeah. They did have that, and I used that, but Merck came through a different connection, and this goes to networking. In Santa Barbara, I had overlapped with someone who was a grad student there in the same group, but she was married to a guy who's working at Merck. And he came over to do some stuff, and we got to know each other. And he fortunately became my first boss in industry. He hired me. And it was at the end of a hiring freeze. So it took a little bit of time, but he persevered, thankfully. And I'm so grateful for that because I just loved that job. It was the only time I really kind of had to look for a job, and that was a best-case scenario for me to get to go to Merck.
Outro - 00:24:06: That was Örn on early experiences and mentors that set his direction. Next time, a visa problem sent him from Merck in Pennsylvania to a UK lab while a chance connection opened a door to Transform Pharmaceuticals and an eventual Johnson & Johnson acquisition. If you're enjoying the series, follow the show and share it with a friend. See you next time.
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.
