Founding Infinimmune & Developing Breakthrough Tools for Antibody Discovery with Wyatt McDonnell

Welcome to the Axial Podcast. Axial is an early-stage investment firm based in San Francisco. We partner with great founders and inventors investing in early-stage life science companies, often when they are no more than an idea. Axial is fanatical about helping the rare inventor who is compelled to build their own enduring business. Hey Wyatt, we're recording. We've spoken for the last 15 minutes now. Yeah, I remember the second time we met, we took like a 6-hour walk. Yeah, this won't be a 6-hour podcast. It'd be like 40 minutes because you're pretty busy. Um, I'm good to have you on. Um, you have one of the great stories in biotech, and it's going to get better. Uh, maybe you could do a brief introduction on yourself and Infinite Immune, and then out the gate we can just focus on what you're hiring for so people know.

Yeah, yeah. So thank you for the super kind introduction. I actually, when people ask me about you know, how Infinimmune raised a round in sub-3 months in 2022. It actually starts with that walk with you because I think, you know, you were our very first committed, in the thick of it with us investor. So we really appreciate the support on that front. Infinimmune is— we're the company that is taking a fairly obvious thing, which is that the human immune system produces antibodies And we're translating that into drugs because most of the clinical need nowadays is not on the safety front. Safety is the largely commoditized and solved problem. It's not on the finding a binder front. There are many excellent technologies for finding an antibody candidate that binds. It's on the efficacy front. So we're working with samples from extremely interesting human survivors of autoimmune disease. Cancer and oncology and infectious disease because human immune system produce antibodies that other immune systems and display systems don't. So it's a kind of obvious thing, and there's a lot more sort of how have we gotten to the state that starts in 1973 with hybridomas, but that's Infinimmune, and, and that's what we're working on. So we're moving antibodies from you or me to patients around the world. On the hiring front, yeah, we can talk about, you know, forming a team and what that looks like, sort of the, your founders are your first hires, both from the investor side and as an operator. We can also talk about, you know, what we kind of look for in people or the roles that we're looking for in the coming year. I don't know if you want to start on one of those three. I can start with that.

To be honest, I think, what roles are you hiring for? I mean, you're hiring for smart people in general and immunology junkies, but any specific roles?

Yeah, so we actually, we try to be cautious when hiring immunology junkies. Because immunology is this, you know, it's really this very beautiful artistic science. There's still a ton of unknown things. There's a lot of findings that were discovered in the '80s and then never chased down because tooling like single-cell sequencing didn't exist then. So where we're focusing on our talent needs in the next calendar year, we're looking for folks who have an interest in building tools that are normally used much later downstream in drug discovery. So more in the lead optimization front. So we'd like to bring some of that upstream into our screening pipeline. So if you've worked on things like viscosity formulation and you have thoughts on how you'd want to try and do that at a much different scale than the sort of grams per liter scale that you worked at previously, we'd love to hear from you. We are going to be spinning up a search within the next year for a chief business officer and some business development folks who want to help us ship some very unique assets and partnerships out the door and make use of the momentum we already have on that front. And then separately, we think that tool builders are very rare individuals. So if you have built a tool that studies antibodies as a protein product, or if you've built a tool that nobody else has built in the sequencing space, or worked on a really impactful product dev team at companies like Illumina, 10x Genomics, places like that, we would love to hear from you and get to know you because, you know, we think tool builders are very rare and we want to bring as many of them in-house as we can over time.

Cool. Well, everyone should check out Infinitum and we'll put the job description in the link. Yeah. And email Wyatt, email me, and they're going to build up an awesome lab in Alameda.

So yeah, we've got a shiny new 10,000 square foot lab opening in April and we've got killer corporate benefits. And most importantly, We're a small lean team, so we have a flat org and we don't have bureaucracy or anything like that. You can come do the science you want to do. It's very fun.

Well, now we have kind of an initial basis on Infinite Immune. I think let's talk about the story that led to Infinite Immune.

Yeah.

You have one of the most fascinating stories of any founder I ever met in terms of like a great origin story. And you built yourself— Infinite Immune is 10 years in the making, not necessarily a thing. You just had an idea and you started it. You kind of built a career to get to this point where you can build a team and set the vision and actually execute. And so maybe we can talk about where you initially got interested in science. And yeah, from my perspective, what's really fascinating is you went to Hillsdale College. I think that's in Kentucky, right?

Uh, it's, uh, politically it might be in Kentucky, but it's actually in southern Michigan.

So yeah, it's, uh, So like, maybe we could start there, but more generally, how did you get interested in science? You mean all of them?

Yeah, absolutely. So yeah, I think my early interests in science, there's actually a photo of me in a lab coat at like 6 years old in the lab of a family friend whose son ended up doing some writing for Breaking Bad. This chemist ended up doing some consulting for them, and the first sort of magical thing he showed me was a redox reaction. That took a standard copper penny and silvered it or, you know, gold-plated it. So it's like, wow, this is like watching alchemy unfold. Super interesting. My, you know, neither of my parents have a PhD, but they both were huge advocates of a ton of just interest in reading early life. And through middle school and high school, I spent a ton of time in the library. I spent a lot of time doodling on sort of natural history and nature. And I always had an early fascination with viruses and immune responses against viruses. So I guess I forgot all of that when I went to college. I went to college thinking I was going to double major in biology, some niche of biology, and also piano performance. And I still play piano. I'm still better than average. I'm not a top 1% or maybe not even a top 10% piano player now, but I, I can play better than you might expect. I think that's pretty common in a lot of creative biotech scientists that you sort of meet at this stage. And Hillsdale is sort of the place that made a lot of that possible because it was such a small student-to-teacher ratio. So I think around the time I went, it was maybe 8 or 9 to 1. The largest science class I took was maybe 60 students, 1 teacher, in an intro-level bio course, similar organic chemistry. And I started in organic chemistry as a freshman, so I took all this AP credit, transferred it in, and said, okay, the world's my oyster. I can take a ton of science that you normally don't have room for in a bachelor's degree. And what did I end up taking? Well, I took stuff that sort of let me wander through all of these disciplines that I found interesting. I didn't care much for general chemistry. It's like, okay, linear algebra is fine. I don't find that super exciting. Organic chemistry, you know, I think you've spoken with some organic chemists on your podcast previously. It's like, yeah, memorization won't help you here. It's about learning function. It's about learning concepts, right? So you're not going to be able to predict how individual things perform form. That's super satisfying. And then I landed on my, my first sort of career-long mentor, Frank Steiner, in the bio department there at Hillsdale. I took 4 years of classes from him. I ended up taking microbiology, immunology from him as well. I took a special topics in immunology course, ended up writing a 15-page term paper on state of the state and HIV vaccines. Found that super intriguing. They hired a whiz kid professor. I took virology my last year of college. It's like, okay, wow. So I've had sort of the requisite sampling courses that you might see in grad school, from cell biology to genetics, all the way through. The micro and immuno stuff clearly piqued my interest by far and away, and I also got a chance to do, you know, in the lab, hands-on work for 3 of the 4 years I was there. So by the end, I could actually do something useful and sort of had a, a head start on going into grad school. I, I didn't have to learn how to pipette for the first time or anything like that. I'd done PCR, I'd done phage display, I'd done, uh, microcultures. I'd, I'd done things like that that you don't always get a chance to do. I thought I was gonna go to med school. I caught the research bug way too strong in college, and to my mom and dad's, I think, a little bit of chagrin at the time, I did not, but I think it's worked out pretty well based on, you know, applying to about 30 grad schools, interviewing at about 15 of those, and I took an offer at Vanderbilt University from there.

At this moment, I totally agree. Being a scientist, from a parent's perspective, is like 'Are you going to make how much?' That seems a little safer. Getting a PhD is a pretty risky decision. It's not marketed that way, but maybe it should be. But maybe at that moment in time when you're in that transition period from college and after college, what was the kind of— what was your vision at the time? Was it, 'I'm all in on science,' or was it like, 'Oh, maybe I'll do science and I'll get a job'? Yeah, at that moment.

Yeah, so I think you're right. I think when I was younger, I don't think I really understood the sort of career market going into a PhD. It was like, well, you know, I, I went into a PhD program because I wanted to learn how to create knowledge rather than learning how to execute a protocol that somebody else has written and done all the tinkering and figuring out. About my first or second year in grad school, I was looking at career outcomes from the Biomedical Research Office at Vanderbilt, BRETO, which is very good. They were bringing in folks from locally and also from around, you know, they're just various zip codes from the alumni program, so you could play, you know, people who would be program officers for NIH, like, okay, well, I don't really want to review grants right now. I don't, I don't like grant writing so much. Interesting, you know, I liked I liked seeing a stream of information, which is, I think, probably a pretty satisfying thing that you get to do in investing as well. I had a very good friend, Ian Settler, who had actually come back to grad school from a consulting career in Deloitte and was like, wow, you know, there's actually a whole new lens that you can start to view science if you're building a career around a PhD. Like, you should actually, I think, If you're going to do a PhD in STEM of any kind, my recommendation would be to look outside of the ivory tower immediately and start finding people in industry with PhDs doing work. Because that was sort of where I landed at the end of grad school was, wow, there's all of this really incredible set of tools to work on now that didn't exist in the '90s or the 2000s, certainly not earlier. The applications of those tools are boundless. The adoption of those tools slow, even in the best and most innovative pharma. It's a really interesting opportunity to learn there. And by the time I came out of grad school, I'd learned how to program both robots and some terrible Python and R code. I wanted to know what industry was like. I found myself in a great position at 10x. I'd actually made some GitHub corrections and suggestions to some code from who would be my manager at 10x, surprisingly. So that worked out pretty well. And yeah, I flew out to industry interview for the first time and was sitting here in California going, wow, I just flew into San Francisco. I'm driving a rental car off of McDonald Drive by SFO. That alone feels like a pretty nice little bit of luck to see my last name in a future home, right? So drove out to interview at 10x, had a Super interesting day. It was maybe 100, 103 degrees outside. I was boiling alive. And then I got my brain boiled by all of these incredibly smart, kind, interesting people and was sitting here going, wow, that's a level of talent that I have just not seen concentrated in academia before. I think this whole industry move is totally the right thing to do.

Cool. Okay. Maybe we can speed it up too. You go to Vanderbilt. Yep. We'll talk about it some other time. Vanderbilt is one of the best infectious disease programs in the world.

And so it's exceptional.

One question is, you know, in terms of your— the theme of your work. Yeah. You always know it was going to be immunology related, human immunology related, or did you—

Yeah.

Virology, like, you know, how did you orientate yourself? What were the key moments where you figured out these are the big problems I want to work on?

Yeah. So I think the key moments were during the two rotations I had that ended up leading to my home labs for grad school. So one was in the labs of Simon Milal and actually his wife, who is also a physician scientist, Elizabeth Phillips. So they were recruited to Vanderbilt to build some very cool precision genomics. And I would say they're uniquely qualified to do that because they translated into global clinical practice this T cell mediated test. So if you are newly HIV positive, you're going to be tested for HLA-B alleles. If you have the B 57-01 allele, thanks to Simon and Elizabeth, you will never receive abacavir as your first-line medication because your T cells might burn your skin off. So I rotated through that lab and went, wow, they have a lab in Tennessee, in Nashville, 12 hours around the world on the other side of the globe on the western coast of Australia, they have a sister lab. It's a 24-hour research operation with identical robots in both countries and in both lab setups. So super incredible exposure to what investing can do. So they actually got started with some Gates money foundation in the early 2000s and turned that into this incredible set of patents and most importantly basic research findings that translated. And the second group was newly started actually that year by Evelin Georgieff, who had spent the past 7, 8 years at the Vaccine Research Center at NIH, had done all of this incredibly compelling work on broadly neutralizing anti-HIV antibodies. And, you know, the other rotations I did were, were interesting, super interesting bookends, but human immunology, there's just clearly such an unmet need in that space and so many basic things that were clinically important and totally misunderstood. That was when I was hooked. And yeah, so I figured learn from a T cell person, learn from a B cell person, learn from a technologist, learn from a clinician. You can't miss if you're getting that kind of exposure as a grad student.

That's awesome. Okay, so speed up. You interview at TEDx, and TEDx is definitely like one of the epicenters of like new genomic tools, and I think there's gonna be all these alumni starting companies over the next decade. Uh, there are. And so, um, why choose TEDx, uh, out of maybe all the options you had? And yeah, some of the initial projects you were working on.

Yeah, so I did have a couple of non-10x offers going into industry, but 10x was personally compelling for me because I had, you know, my, one of my PIs at the time ran the genomics core at Vanderbilt, and that core had a 10x Chromium controller and also a Bio-Rad DDSeq. So there were a couple of labs on campus that were hacking at DropSeq and, you know, that was okay. And, but they were, it was basically a boutique technology that somehow never found its way out of those labs into others on campus. And then sort of watched the uptake of the Chromium controller and the 10x solution by all of these labs. And I think there were maybe 2 labs that were doing a consistent amount of single-cell sequencing when I started in 2015. That has got to be in the '50s, '60s, higher now. And it was all driven by the Chromium controller. So I sort of watched the DDC gather dust, watched everybody and their cousin run the Chromium controller. And then there was the sort of like analysis bottleneck. So a good chunk of my grad school papers were just helping to do some analysis and being a bioinformatics middle author for folks that had done some hard-pressed experiments, having some hard-to-find clinical samples, but weren't sure what to do with their genomics data. So it's sort of a no-brainer to me to take an offer from 10x because I had watched them take the market in a genomics core in front of my eyes. People were coming back to use the instrument. Like, that doesn't happen with life science tools very often. There's a lot of private tools that people don't like enough to use again, and then you sort of get this like academic cost of mongering where people will put an instrument on a blacklist and, you know, you never find out why that instrument is never used. But that was not the case with the Chromium controller. So to go build solutions on top of that and learn from actual industry scientists how that process worked. It was a super easy choice to make, and they were pre-IPO at the time, had just closed, I think, Series D. So it's like, well, you know, if you're in your 20s and have an opportunity to hit an IPO jackpot, that's transformational. I recommend everybody try to do that if they can. It would really change your life.

Yeah. Okay. So maybe I was in grad school when 10X launched Chromium and I just remember in 6 months, maybe even a year, just blew up and it totally displaced Fluidyne and all these other legacy tools and it just was so much easier to use. Yep. And like you said, people just kept on using it again and again and it just revolutionized that field. Okay. So I think you joined 10X 2018 or '17?

2019.

Yeah. Yep. Okay, so you move out to California. Yeah. On a personal note, how do you like California? It's so totally different than Vanderbilt. Yeah. To Michigan, uh, you go to Pleasanton. Like, what was the kind of the, uh, have you seen yourself change personally? You know, you know what I mean? Like, have you become more laid back, or, you know, is it— what's—

how has California affected you? California, you know, I don't think it's— I don't think it's— I wouldn't say it's affected me a ton, but I have to say Growing up in really harsh winters, I'm very appreciative of the weather. Having been a broke grad student in Tennessee, I'm less appreciative of the state income tax. But I think, you know, if you're hiring and if you're trying to build something, San Francisco is just such a clear talent hub for so many places around the world. You know, I really feel that I don't know how much I buy this biotech will be decentralized argument because there are physical talent hubs for bio and biotech in the world, and SF is one of them. So it was kind of like being hooked up to an electrical feed, like, oh my God, there's so many smart people here everywhere for, for any problem you could want to solve under the sun. So it's been a huge growth opportunity for me because I have an opportunity daily, weekly minimum, to talk to world experts in all kinds of topics. And it's hard to get that exposure if you're not in a place like this, and I don't think I had an appreciation for that when I came out here to the extent I do now.

Yeah. San Francisco, I think you have success anywhere because the opportunities of that. But if you're a new entrant, like an up-and-coming person, totally nice to be. I, you know, if I was in Boston, yep, I would be lame probably. I wouldn't have any success. Even here, this, there's, you know, less barriers to interact with people. I still do have to do the work, But San Francisco, you're a new entrant, you'll get a shot at least.

Yep.

Yeah. So then other places. So maybe we can talk about 10X. You know, I talked to people who worked at 10X on references and stuff and it was unanimous. Yeah. Why? It's one of the best people I've worked with. And so that's pretty amazing because, you know, 10X has a lot of talented people. And so maybe talk about the pro— you worked on a long list of projects.

Yeah. Just a few.

Just a few. COVID to antibody discovery, epitope mapping. A bunch of stuff. We probably can't get to all of it, but maybe we can talk more about your experience. Yeah, additional projects, getting exposed to teams, what you learned, uh, and that whole journey of being a grad student, joining a company, might be a different environment, right? Absolutely. Academic to industry. How did you deal with that? And then how did you navigate corporate structures and work with different teams and then be able to deliver really valuable work?

Yeah. So, 10X taught me, I mean, I honestly think it's fair to say that if I hadn't worked at 10X and hadn't had an opportunity to earn all of that experience there, I wouldn't have started Infinimmune. I mean, I just think there are so many barriers to entry that you just don't understand unless you work at a really high-quality industry company like 10x. So that there are a couple of things, you know, I started midway through research and development on the second generation of the immune profiling solution. So I showed up in August of 2019 and was trying to learn all of these project management acronyms and trying to figure out, you know, what actually I was going to contribute to this project. I think that I later found out that's a pretty standard experience. So you spend about 90 days just listening and trying to figure out up from down, north from south, and if you can make a contribution in that window, great. That's, that's an incredible outcome. Congratulations. Now you have to repeat it, and that's, that's where you have to just sort of find a working group. And I think 10x, when I started, did a very good job of that. So, you know, it's like, wow, you actually have a dedicated onboarding person who helps you get set up, plugged into your different teams, plugged into your bio person. Where's my compute? Where's my storage? What's our development workflow look like? As a comp bio person at the time, I can tell you, if you want to feel like Kobe Bryant at 11 years old making no shots on the basketball court, It's a very similar feeling going out of grad school and moseying up next to serious software engineers from places like Google and the Broad Institute and being like, wow, I'm a moron. I know nothing. I should really just focus on learning. And so, so that was, I think, you know, my first year at 10x was identifying a couple of problems in product as it was moving out, working with some molecular biologists to troubleshoot and figure out how to address that. Realizing that, yeah, you know, KPIs are a thing for software companies. Some of that does actually translate into this sort of like comp bio working with a wet lab team modality if you're, if you're doing tool building in the life sciences. And then right after that, so, you know, I joined in late summer, early fall 2019. 2020 rolls around and I had started with some, some introductions my first couple of months at 10x. So yeah, and I worked on some cool immune profiling stuff at Vanderbilt that should be productized. You know, I think there are better ways of doing this. I think this could be kitted out in a way that is much less of a pain in the neck for customers and has a fundamentally different set of intellectual property constraints. I found out as part of that process over a couple years at 10x, I ended up contributing somewhere north of 90% of their immunology patents. Learn the difference between an idea, an invention, and a patent, how those things do and don't relate to each other. You gotta work in industry if you want to learn how to do that efficiently and do it well, and 10x's patent mode is real and it's super high quality and very, very inspiring. So going into the pandemic, all of a sudden antibodies mattered in a very, very big way. 10x's customers were the ones creating and shipping these drugs. And actually, uh, 10X was used by one of the Vanderbilt teams that ended up producing the Evushield cocktail. And so that was, you know, sort of one of many proof points of things I've read over the years and watched play out in real time of what an antibody from a human can do. Um, myself and, you know, actually David Jaffe, who Interviewed me my first day at 10X, and then he and I ended up working closely together on the immune repertoire product. David wrote most of the key underlying code in the sort of antibody TCR suite, which we put on BioRxiv and GitHub called nClone. So he and I worked very closely doing this sort of proof of principle with barcode-enabled antigen mapping. So that turned into the TCR and BCR discovery product that's now sold by 10x. And as part of that work, we also protected a broad set of really interesting human-derived anti-COVID antibodies. Brian Briny and some collaborators at Scripps are sending that out the door in the near future to a journal near you, somewhere in the Science or Nature family. And, you know, I think that was just sort of how I and in 3 years' time went from can't develop serious code or do a code review to can at least stand on my own two feet and know up from down on that. Learned how to work with lawyers and everybody in between you and R&D and the lawyers as a scientist to put a patent portfolio out there, how that integrates into existing patent strategies, and most importantly, realizing how hard it is and how many different types of disciplines and how much expertise you need to build a transformational life science tools company. I think companies like 10x are exceedingly rare.

Yeah, yeah, yeah. I think tools are more rare than therapeutics. Oh, absolutely. Yeah, hands down. Yeah, so much harder. Like, a tools company happens every 10 years, maybe. Yeah, if that, if you're lucky. Therapeutics can happen every— there's so many— it's just the market size is so much bigger. It's a little easier. It's more fundable and people are more willing to take a shot on it versus tools. It's so complicated sometimes, but when it does work, it really works. Maybe we could talk about, you know, 10x, working on all these projects, meeting all these great people. Yeah. How did you— often when people work at companies, like, you get siloed off. And then you just kind of like working, working, working, working, working, and you kind of lose what's the meaning and kind of become very, you know, just be honest. And so you figured out a way to resist the overtalk and ideas. How did you do that? What was the trick? Was it talking to a lot of people across silos or was it what we were doing work at TEDx? Without getting stale at the same time?

Yeah, I think I got lucky because at the time there were, including me, not more than maybe 3 people at the company that knew anything about a T cell receptor or a B cell receptor, so I kind of started off on a good foot with having a niche, particularly useful set of expertise available for people who were trying to solve problems, not just in product development, but also in business development, for instance. So I actually went on a couple of, uh, not roadshows, but dedicated site visits with places like Behringer Ingelheim, Pfizer Pearl River, Sanofi, uh, places like that where 10x was making a concerted active effort to sell brilliant new tools to folks who had not adopted them yet. And that was really instructive to watch, you know, this sort of like top-down, bottom-up view where you have research scientists talking to each other, you have business folks and leadership trying to figure out how the set of tools is going to plug into campaigns they run to develop drugs. That was super valuable experience and also taught me that a lot of the ways that I would communicate you know, actively daily in R&D totally failed when applied to a new audience. You know, it's like you have to try completely different approaches to explaining concepts. You have to simplify, simplify, simplify when it comes to slides. You have to do what I'm not doing in this interview, which is take a breath and ask more questions than you, than you answer. And I think that was just very valuable experience. I also You know, I think 10x's leadership made themselves unreasonably available to me. You know, I was able to get a meeting with Serge on a semi-regular basis. Ditto with their Chief Business Officer, Ruth Kabacher, when she joined. Their Chief Technology Officer, Michael Schnall, a super busy guy, but for something interesting, he was always available and always found time. So yeah, I think Just being not afraid to ask for a meeting and hear somebody's opinion is the best way to not watch yourself stagnate.

Cool. Yeah, I think that's really good actually. I mean, having expertise that's really niche in your organization that allows you—

invaluable—

allows you to like operate across all these cross-functional teams and you get exposure. I just have friends who work at like Novartis or Merck or Alumina, they just get siloed off and then, yeah, it just gets sucked into a 5-year rabbit hole and they never— yeah, yeah, it's tough.

And I, I also think it's valuable to recognize the, the limits of that expertise, right? Because it's, it's super useful in the sense that it gives you an opinion. Opinions are not actually so common, like trying to track where an opinion came from in life sciences is usually fairly hard to do, but it's not often that you find people with surprisingly strong opinions and convictions on a thing. And it's also important to recognize that, you know, expertise in one area, like VDJ immunology for me, doesn't translate to expertise in other areas. And that's really where this sort of like interdisciplinary team building that 10x figured out how to do at speed and at scale becomes super, super important. You have to, you have to hire people who are smart and also know exactly when they're going to drown and they're open, you know, they're out in open water.

Yeah, that's awesome. Okay, so maybe it's a great transition. Yeah, absolutely. And so you leave 10X in summer of 2022. Then you start Infinimeme. Yeah. Can you talk about the initial motivations? Yep. Kind of the, you know, on this point of, you know, strong opinions. Yeah. What's the kind of the core differentiator in terms of Infinimeme's vision of how it should be developed versus maybe conventional strategies?

Yeah. So I think there's a, there's a lot that goes into that, but I'll try and stick to a couple of core concepts that I believe deeply in which drive all of the R&D that we do. The first is that we still don't really understand much about immunology, even though we have stories dating back to, you know, Jenner and smallpox with some understanding of how immunity works. So we might understand a little bit about immunity, but we don't understand nearly as much as we could. So if you think that immunity is still a poorly understood phenomenon in the 21st century, why is this? Well, adoption of really cutting-edge tools like 10x, you know, 10x, yeah, you know, they will constantly say we're just getting started. And I think one thing that's very true about that is even though those tools are, you know, I think relatively well established for most life science tools companies, they're still not being adopted and incorporated and thought about deeply at the rate that they could be because science actually moves pretty slowly at the end of the day in a lot of places. So the tool users are not really understanding the tools that they're buying. That's, that's another core point behind Infinimmune. So if you think immunology and immunity are largely not understood, the people who use the tools don't understand necessarily how the tools can be best used, And then the last component, that the best antibodies will come from humans and not other sources, that's sort of the, the trio of the, the stool that Infinimmune sits on. So that last bit, I think, is, you know, I think would have been hugely speculative and rightfully shot down in the early 2000s, definitely even the, the early 2010s, because of a lack of tooling, a lack of basic research, but there's an incredibly interesting and powerful set of literature and also now emerging drug assets that are human-derived antibodies that are unique in this space. So whether it's antibodies are bulletproof longer against something like COVID if human-derived, whether it's you can achieve durable suspension and suppression of HIV infection using a human-derived broadly neutralizing antibody, or more intriguingly, whether you can use something like a human-derived oncology antibody to treat non-small cell lung cancer. And there's some very interesting wins in that space from relatively small labs at places like Duke University. So Infinimmune is predicated on this long-term bet that if you were to take an antibody out of a human for a given indication, it will beat an antibody from a different source, even though in vivo antibodies derived from immunization are always best. There's something about that extra human component that's better. And you can see this not just with Infinimune, but at late-stage companies too, like AbSci, who have figured out, you know, humanization and human-like scores matter on the human antibody perspective. I would speculate that's why Josh Meyer ended up being one of our angel investors in Infinimind. This human component really matters.

Yeah.

Awesome.

So maybe we can also talk about then, like, this concept of on the team building side. Yeah. Really fascinating framework you have is tool users outnumber tool builders by some massive number. Yeah. And this is why it's probably slow uptake of tools from TEDx.

Yeah.

The best people to build applications on top of tools are tool builders, as you know.

Yep.

More familiar. Can you talk about that initial formation of InfiniteMeme's team? And there's 5 of you.

Yeah.

Yeah. Big fam. How did you think about who to surround the company with? And again, to kind of think about that concept of tool builders to make applications and how interdisciplinary everything needs to be. And you got your original interview, David, to join.

So yeah, yeah, yeah. So I think for us, and we, we recognized early on, uh, you know, I, a couple of folks that are co-founders at Infinimune had left 10x before I did. I'd worked with them in varying degrees, uh, while at 10x, but, you know, aside from David, not on projects directly. And as I was thinking about, you know, who would you want early in a company that would have long-term skin in the game and would contribute key expertise that you need when you're building in this space? Well, you need folks who have worked on tricky-to-handle samples. You need folks who have taken one platform and tricked it into doing something else. You need folks who are, you know, I think, I think you should have a spray bottle anytime in the Valley says first principles. But if you can find people who build from first principles and say, well, you know, I don't actually think we understand why this product or this enzymatic reaction is proceeding the way we think it is. So that sort of tells you up front, well, you're going to need folks with some general expertise and some niche expertise. Who have built something compelling. 10x as a platform for InfiniMune was a very obvious and easy choice because that core tech is so, so good at its primary purpose, which is partitioning single cells, capturing high-quality, consistent single-cell data. We felt we didn't want to reinvent the wheel for that. And if somebody else builds a better tool than 10x, great. But in the meantime, it was obvious that that was the platform we were going to build on. So hiring some wet lab folks who were tired of building tools for life science consumers, that was a no-brainer. And there is a limited number of folks like that in that category who, you know, I passed my own sort of reference checks and work history experience, right? The opposite end of that spectrum is sequencing data is so expensive, you need to be able to extract every ounce you can from it. Like, if you, if you think there's Troy Golden sequencing data largely it's telluride and fool's gold, right? So there's a ton of noise in there. Need to find people who will work at the raw read level forward and who have mathematics, computer science, and lastly, lastly, comp bio expertise. Actually easier thing David, one of our co-founders, has taught me, and there's some great examples of folks like this still at PennEx. It's easier to take a physicist or a mathematician and teach them the relevant bits of biology than it is to go backwards and teach a computational biologist or a biologist mathematics and physics.

Right. Yeah. History. So all the Watson and Crick were physicists.

Yeah, exactly.

I never met a biologist who made a new physics theory or something.

Yeah, exactly. And so that was kind of wrapped around this, you know, I think kind of a a mock-up of how 10x does product development, where you have this interdisciplinary expertise up front. And most importantly, people on your team are not going to stand on deck and watch you flail in the water. They'll dive in with you and they'll actually swim with you and teach you how to swim, right? So, you know, I think that was a no-brainer to say we need folks who are experts in the wet lab, who have a track record of building at multiple companies, and not just 10x. And we need folks in the dry lab who have thought about a lot of these problems and can also break something down at the most basic level and say, is that right, from step one, and then iterate.

Cool, that makes a ton of sense. So I think a lot of platform biotech companies, the first problem set you have to solve is getting and generating data. Yeah, you know, because there's a lot of public sources, but it's often not built in a way that creates good models. So for Infamune, how do you think about acquiring patient samples from rare events and processing them? Maybe go back to Vanderbilt, but how do you, for Infamune, a key, you alluded to this, is rare immune reactions where you find survivors, you find people who are resistant to Alzheimer's or something, You find these kind of— what's the best type of mutation? It's a loss of function protective, right? Maybe opposite, but there's a loss of function protective. Exactly. So then that kind of is very much like those are the holy grails of drug development. And so how do you find those holy grails in samples first? And then how do you think about generating enough data in the first place? Yeah.

So there's sort of— two prongs in Infinimmune R&D. One is the sort of antigen-forward approach where you have a target in mind, you can go spearfishing in not just diseased humans but also healthy humans because, you know, I think a lot of antibody discovery has been done from this. Where there's smoke, there's fire. But if you're only ever looking for smoke in the sky, you don't find these sort of interesting protective autoantibodies, right? So, so that's the sort of antigen forward component. The other is starting from, you know, what are effective antibodies doing in the human body, and, you know, what are these products of the human immune system doing? There's very few compared to the number, you know, say about 3,500 surface proteins that your average B cell can be exposed to crawling around you. Maybe 70, not more than 90 of those targets have been drugged antibodies to date. So we're also working on mapping in folks who have had an exceptional clinical response antibodies back to their targets in the human proteome for first-in-class, best-in-class antibodies that were proven functional inside the body already. So then the third component is how do you source the samples going into either of those arms, right? And I think there's, there's a ton of utility and partnership. I think a lot of focus around partnership is late-stage companies that have been through large financings, have been through an IPO, and now they're at a point where they can start to command real premiums at the table for partnerships with, you know, institutions like Intermountain Healthcare or Mayo Clinic, or maybe you go to Tempest. So you're already working with physicians, right? As an early biotech company, you don't have any of those benefits. So it actually can take quite a long time to secure those partnerships. So you kind of need to focus early on figuring out who that partner is going to be for you. And the reality is you can also build very, very early your own sample sets because samples are cheaper to procure than you might think. So where a partner might tell you, well, it's $15,000 for all of these assets, you can actually get the same samples, tissue plus blood, for several thousand dollars directly and even prospectively from a lot of the CROs in the United States. So we actually have, uh, the sort of partnership is, is great approach. Partnership is difficult and time-consuming. We get our own samples prospectively for some of these key indications. And the third source are these small patient foundations. We have patients with rare disease. They all know each other on Facebook and Instagram. It's a small tight-knit community. And they are itching to do anything useful with their blood. So if you have somebody who has an immune-mediated condition, odds are there's a patient support network or group and you can find all those patients in one source. And those foundations are ready and willing to work with companies like Infinimmune to make a difference and do something new.

Awesome. Yeah, that makes a ton. I think for any startup, just data acquisition is such a pain in the neck. It takes somebody—

Oh, totally.

6 months to a year of I can imagine right now, phone calls or CROs, biobanks, and trying to establish MTAs. There's a big opaqueness on pricing. It'd be awesome for every startup if sample pricing was clear.

Oh, yeah. So, I mean, this is one of those things where the other thing that's messed up is where's your easiest path to an incredible drug as a startup? Well, you go for the traditional route, which is an orphan or rare indication, right? So you build this sort of like product as a pipeline view where you start with something that's rare and autoimmune mediated, translated into a new direction. You can see how this is being done with Nipokalumab, for instance, targeting FcRN. Alexion's complement targeting assets are great examples. It costs so much money to get those samples traditionally for these rare diseases. So the wider you can get, the cost of your sample acquisition is going to go down. And in some cases, if you can just say up front directly to these contract orgs, you know, we'll pay per year for an allotted number of samples. We want first dibs on anybody coming through these indications. They'll usually do the legwork for you and you get access to those samples and with a a lot of these samples, once they're yours, they're gone. Nobody else is going to have access to them. So for us as a company, human immune samples are incredibly useful and they're sort of long-term banks of value, right? And I think this is why we were thrilled at the opportunity to work with you because you understood as an early platform company building its own assets, which samples to screen when and at what volume makes all of the differences you grow as a company. Totally agree.

You get the benefit from the clinical trials —yep, exactly. That's what, that's what makes Infinite Immune a lot more interesting than other antibody companies. Maybe we can talk a little briefly about, like, I mean, we're gonna— 2 years from now, we'll talk about all the progress you've made. Yeah, like, maybe the logic or framework in terms of, uh, antibody discovery, you know. What's your thoughts on, like, a monoclonal versus trying to make more complex formats? Specifics and other things. And how do you think about indications? And immune-related disorders are a very broad set. How do you think about figuring out, do you go after a rare indication? Do something in cancer? Do something in neuro? What's your logic right now in terms of building out the initial product set and indication set? Yeah.

So we're also fortunate to have a really, really good lead investor from our most recent round, Playground Global, who you actually introduced.

That's Jordan Playground. He's incredible. Jordan Playground, incredible investor. Talk to him. He's awesome.

Yeah. And so, so Jordy said this thing, I don't remember, it might have been on Alex Ventures podcast, maybe a couple of months back where when you have an incredibly compelling, hard to build elsewhere technology, you can actually go to market. Like, marketing is a solvable problem. You can create a market. It's hard. It's not impossible. And for us, thankfully, it's not nearly as difficult as creating, for instance, the single-cell or spatial or in situ markets because we're not a tools company, right? So, Drug markets are harder to understand because you can buy these databases like TABS, for instance, where you see every antibody that's ever been developed against every target ever, the status of it, is it in clinical trials, how many patents are around it, and you don't know if the reason your interesting antibody against a new target has no competition is because it's a bad target or because you've actually gotten lucky and hit gold, right? So there are actually really, really excellent sort of industry veterans who go into targeted consulting for both platforms and for targets. It's really good to find out from your investors who some of these names are. There's really only maybe 5 or 6 of them, and so it's good to get those folks involved in the conversation early just so they Know how your platform works, know who you are, so when you have an interesting asset against a new target, you have somebody that's not you to tell you if you're drinking your own Kool-Aid, right? So that's, so that's, so that's one part. The second part is finding interesting clinical samples comes down to reading literature. Like, you have to know, for us for instance, all the different types of autoimmune disease and all the kinds of healthy autoantibodies that can arise in lots of different settings. So you kind of have to do like, you know, not continuing education, but you do have to have your finger on the pulse. And then separately, platform companies are really at the end of the day, you know, compelling. But I think a lot of people in the current market, you know, I think a thing that I would feel comfortable regurgitating is that if you have an asset and a platform, The platform is only as good as the asset and vice versa, right? So you have to really have a compelling drug candidate to say that your platform is of meaningful value and utility to investors and future partners. So we have focused on figuring out what sort of those criteria are for various assets and various indications. Like, you know, I think if you were to say, well, we're going to build a company around CD3, If you aren't looking at Tenniobio and figuring out what were the boxes that their CD3s ticked to be, you know, the best thing you could marry into a bispecific, then you're not doing the right kind of homework, right? And so in Finimmune, we're sourcing antibodies from humans. That doesn't mean we do no engineering. It does mean that the engineering material we get is better because it's coming out of an in vivo response, right? So I think a lot of antibody companies have this mindset of, you know, go to Google Images, type in antibody discovery workflow, and you'll see basically one of three things. It's like, go make a hybridoma, screen some serum, find your binder, go do a display library, screen with your binders, negative selection with stuff you don't want to bind to, you have your candidates, and then maybe you get some like 10x as a, you know, input from basically the same systems. And At the core of all of those are immunizations. We still don't understand how immunization works. Immunization is its own real hard game. You can see this with, like, for instance, the difference in FDA approvals for the new RSV vaccines coming from GSK and Pfizer, right? Core technology underlying is not so different, but the efficacy and the safety outcomes look to be, you know, by FDA reviewers different enough they're comfortable approving one for forward movement and the other doesn't go. So we're trying to circumvent that by going straight to humans because the body has already developed an effective functional response, and we don't have to figure out also in parallel the art of immunization. You know, and I think if you're an emerging MD-PhD or a young PhD scientist who's found some clinically incredible target, you have validation on that target, for some reason, there's no reason why you should do the kind of work that we're doing at Infinimmune. You should go to an ecosystem company like Alloy Therapeutics, and you should use a transgenic animal and generate your binders and use that to get to the clinic rather than trying to build a platform around a target.

That makes sense. I think there's kind of a— depends on, like you said, the target indication. Yep. And Some are gonna be more amenable to a technology that doesn't need a great antibody. Yep. And some targets are so intractable and hard, you need the best antibody. And that's where Infomune comes in and discovers the best antibody you can ever discover. And so I think one thing, just talking to you, I think you're gonna become on the board of trustees of Hillsdale one day. And that'd be really cool if you manage their endowment. Bob Noyce from Intel. He became the board of trustees at Cornell. He grew up in Iowa, a really small college. He actually made it into a billion-dollar endowment or something. Some massive— I think you're in a collision course to Hillsdale board of trustees on this point of your journey so far. And then we'll do updates and see how it's going. Yeah. Any kind of key lessons you've kind of pulled out so far, like in terms of choosing a career? Starting?

Yeah, yeah. I mean, I think if you've ever thought for a split second about working in industry, you should just go work in industry and give it a shot because there's still substantial financial upside for you, even if it's not what you do at the end of the day. You're going to get exposure to all kinds of things that will be difficult for you to see outside of an academic setting. If you've thought about starting a company, now is an incredible time to start a company, and if you're going to start a company, just be prepared to, you know, have things go wrong when you're started and post-operating and, you know, post-financing like us, and certainly before those wires ever land. So it's really about being open-minded being willing to entertain new ideas, but also having a pretty clear vision of how what you're working on is going to change the world at the end of the day. For, I think, for, for us, you know, I would say as not one of our investors, I think our team is incredible. Yeah, the team you build with the company at the beginning is really where most of the investment decision is made, at least from, from our side of the table. We feel like We were a team-based investment, and in retrospect, I think all early biotechs are an investment in a team. So focus on building a really high-quality team and focus on finding and learning from really talented people and figuring out who's going to work with you, because that's what will or won't make it go at the end of the day.

Cool. Okay, great way to end it. Great story. Yeah, appreciate the opportunity. Absolutely. We'll catch up offline, you know, but we'll do this 2 years from now, and then looking forward to it, year 8 or 10. Oh yeah, why? Really successful. It's gonna be really awesome. But, uh, thanks for doing this. Uh, yeah, my pleasure. I really appreciate it.

All right, thanks for the time, Josh. Have a good one. See you soon.