Chris Moxham - Part 3: Embracing Startup Life & Leveraging AI & Genetics in Drug Development

Intro - 00:00:01: Welcome to the The Biotech Startups podcast by Excedr. Join us as we speak with first-time founders, serial entrepreneurs, and experienced investors about the challenges and triumphs of running a biotech startup from pre-seed to IPO with your host, Jon Chee. In our last episode, we spoke with Chris Moxham about his move to Eli Lilly and how the work culture contrasted with his previous role at Wyeth. Chris also shared how his early experiences at Eli Lilly shaped his career path. Lastly, Chris recounted the challenges of leading a multi-million dollar lab build-out in New York City. If you missed it, be sure to go back and listen to part two. In part three, we talk with Chris about his leap from Eli Lilly into startup life and the mix of excitement and uncertainty that came with joining a smaller company. We also dive into the learning curve of working with investors and how Chris mastered the art of communicating science in a business context. Lastly, Chris gives an inside look at building Transcriptor Bio's Discovery Engine, a scalable approach to drug discovery that combines AI, genetics, and high-throughput data to reduce failure points in development. 

Jon - 00:01:23: You're wrapping your time up at Eli Lilly, I guess. And then you're about to go into biotech land startup, like not startup, but like not Eli Lilly land. Can you talk about like what was going through your mind? Were you like ready to go, like just locked and loaded? Or did you have some reservations about, you know, kind of going into a, you know, a smaller company and kind of what that might entail?

Chris - 00:01:44: Yeah, I mean, look, you know, I was at a Big Pharma company, right, that had all the bells and whistles in terms of security and benefits. And. You know, security isn't, I guess, what it used to be always at Big Pharma, but I was happy at Eli Lilly and Company. But also, I think it was time for me to make this change. And so for me, there was a bit of, you know, I guess, uncertainty, if you will, just. Well, this company says they have two years of runway.

Jon - 00:02:10: Yep.

Chris - 00:02:10: Seems like that's sufficient. They had a program that was going to enter the clinic. I really trusted the leadership team and the investors. So it just seemed like, okay, let's go for it and jump in. And I'm glad I did.

Jon - 00:02:24: That's so cool. And you mentioned that during this Fulcrum experience, you started to interface a lot more with investors. So like, I mean- I'm kind of like piecing together, like you learn how to manage early, just like by rolling up your sleeves and doing it, you're learning different fields of science on the fly. You're like, I don't know anything about, you know, antibodies, but I'm going to learn. And now you're, you know, I feel like when you talk to investors, that's like learning a second language too. And kind of like, you know, it's a different field. Finance is a different field. Can you talk a little bit about your experience about how did you get good at that?

Chris - 00:02:58: Yeah. Well, you know, and my engagement in those meetings, I was there more to talk about the scientific program, right? And why this was going to be a competitive program and how it could create value and what our plans were. So still kind of in that comfort zone of science and drug discovery. But starting to key in on the questions they would ask. Or directions they would try to take you, and you would want to bring them back to where you wanted them to be. So for me, it was starting to learn a new language, but also do kind of a new dance, right?

Jon - 00:03:29: Okay.

Chris - 00:03:29: I see you're going over here. Well, here's the answer for that question, but also here's how I get you back over to what I want to talk about. So again, it was just learning that strategy, which I really enjoyed, of just kind of this interaction, but also learning about the types of questions and why they were asking them. But again, I also really benefited from like Robert Gould, for example, just kind of at times taking me aside and say, hey, when you get this kind of question, like, here's how you can answer that so that it comes off in a way that, you know, we're not looking like we're defensive, for example. Or, you know, an investor would ask me, well, why don't you share your toxicology results? And in my head, I'm like, because we don't. So I had, again, kind of a hallmark of any, I think, any great kind of career over time is that you've got people supporting you along the way. So I give credit to Robert, for example, in those discussions early on. Helping me kind of come up with the appropriate answers. But then I just started to get the hang of it. And there was a period where me and the CMO and the CEO had like 25 calls in one day, presentations with investors, where we were having a public offering. And we just got into such a groove. Again, it was just, for me, those team experiences where you're just so gelled with your teammates and you know what they're thinking and you can hand off to them. They're going to hand off back to you, whether it was different project teams I was on or talking to investors. It was just such a great experience to be in that kind of setting. 

Jon - 00:05:00: That's so wild. And IPO-ing is such a massive event in a company's life cycle. And I'm honestly jealous that you had the front row seat and had someone who's coaching you as well. And this is how they want to hear things. What was the hardest part about that roadshow?

Chris - 00:05:18: So, you know, when I first joined the company in the IPO roadshow, I really wasn't a part of it. It was actually once I became the CSO and we were out doing another offering, public offering of stock as a public company that I really had that sort of experience. But even there, when I started to do the investor calls, my first couple, I think my questions to my teammates were like, well, how do these things go? Like, what questions do they ask? What am I supposed to say? Like beyond just the science and explaining it. And, um, Like the first one I did, you know, it went well. And my teammate called me. I was like, you did it. Like, that's how it goes.

Jon - 00:05:52: Yeah.

Chris - 00:05:53: I was like, okay, I think I can handle this. I enter it with a lot of respect for the people on the other side, right? Like, and recognize that they, you know, they're trying to make a determination, right? Whether they want to invest in the company and they're trying to evaluate, in this case, our sickle cell program, for example. And so on one hand, you're trying to certainly present the data honestly and accurately, and also try to paint a very compelling story. Like this is something that you should invest in because we're going to win. So I just, you know, like any new experience, right? I usually kind of weighed in. Observing and getting a lay of the land and seeing how it goes. And then you start practicing and then you just kind of take off, right?

Jon - 00:06:36: Yep, absolutely. And I think I love that it gets back to just like having respect for the other side, like that respect and that empathy, just like knowing where they probably have their own priorities and you kind of need to appeal to those. But you can always, as you said, kind of like bring it back to like the science. That's very cool. And I guess as the CSO of a publicly traded company. Can you just talk about how things change when you're from private to public? We hear about it, but you lived it. What is that quantum leap?

Chris - 00:07:13: Yeah, I think the scrutiny over what you say, right? So now I'm participating in earnings calls.

Jon - 00:07:19: Yeah. 

Chris - 00:07:19: Which again, like, I would have thought that would have been me, but. So the level of preparation. But also the scrutiny over what you're saying, right? Again, it has to be accurate and truthful. And it's really about reporting on the performance of the company over the last quarter, for example, or the year. So it was kind of like a heightened level of formality. And I guess, again, scrutiny over let's be accurate in what we're saying. We don't want to create any problems, right? And so I think it's just that element of. Kind of like what I told you my mom said, remember who you represent? Mm-hmm. I think you kind of enter into that realm of like you're a public company now, right? You have to really be mindful of what you're representing, both in terms of just what you're doing, but also how you're performing and where you're going and not to make misleading statements, right?

 Jon - 00:08:09: Yep.

Chris - 00:08:10: And do those things. So it's just another level of another standard, I guess, if you will, in terms of how you operate and how you speak about the company.

Jon - 00:08:17: Yeah, totally.

Chris - 00:08:19: On a day-to-day basis, internally, from a research perspective, it was, I would say, for the scientists involved and the research team, probably no different necessarily. For the management team and, you know, how are things progressing? Right. And how did we talk about what we had? And when we thought we might have our next IND and let's be, you know, think about how we say that, right. Or. Media training, right? And learning to answer questions in a way that, you know, is appropriate, if you will.

Jon - 00:08:51: Yeah, totally. And my wife works for a publicly traded company. And whenever we watch the earnings, she's not on the earnings call, but we're just like watching as she is a shareholder. But I'm just like, when I hear like, there's Wells Fargo on the line and then they just start hammering them with questions.

Chris - 00:09:10: Yeah.

Jon - 00:09:10: And almost like I've never been there, but I'm like, it almost feels like you're getting, sounds like you're getting deposed. Like sometimes. 

Chris - 00:09:17: You know, but you've, many of the people who are asking the questions are investors that you've already talked to many times before the earnings call, like just periodically, they're checking in. So you know who they are, their personalities, and they probably have asked that question before. But there is this element of during the earnings call. If you're all in the room together. Of this eye contact, right. Of, you know, the questions coming in, the CEO is probably going to lead off with just, you know, kind of an opening high level statement to answer the question, but then he's going to quarterback and hand off to somebody, right.

Jon - 00:09:52: Yeah.

Chris - 00:09:53: So you're just kind of looking at each other and I anticipated this question. Okay, it's going to you. 

Jon - 00:09:57: Yeah, yeah, yeah.

Chris - 00:09:58: So it is, again, when you're first in it, it is stressful, frankly.

Jon - 00:10:02: Yeah. I get secondhand stress. My palms are sweating just like thinking about it. 

Chris - 00:10:07: But eventually you just build, again, a rapport with the investors. You kind of understand the questions that are being asked. It's not the first time you're hearing them necessarily. But I think ultimately you are trying to really. You know, stay on the right side of being honest, not misleading anybody in terms of where things are, but also not necessarily having to give away too much as well. Yeah, totally. 

Jon - 00:10:34: And I think, I don't know who, who, who said it, but it's kind of like, and it comes back to like communication, there's like constant communication. But like with investors, you like, you get the investors that you deserve. And like, part of that is like communicating. Yeah. Because if you don't, if you don't communicate correctly, you're probably something you might get the wrong investors who like might've thought, you know, you're going to approach something a different way.

Chris - 00:10:59: Yeah, I mean, I think that's the, you know, yes, getting investors is certainly about. Injecting more capital into the company. But. It's a relationship, right? And these individuals are going to be on your board and they are now part of your team. And yeah, expectations better be aligned going in. Yeah. Otherwise, it's going to be a rough road, I think. 

Jon - 00:11:25: Absolutely. And I think during the kind of go-go's of kind of like 2020, 2021, at least there was a lot of like it almost went, we almost forgot that there's a relationship to investment as well. And it was almost where it's just like big, like at that, I just remember just like, we're big numbers better. Just like, and then who cares who's on the other side, just bigger number better. And it always like was a head scratcher for me. I'm like, but they're on your board. Like. That's not just a monetary thing. 

Chris - 00:11:56: That's like, I mean, I look at it as, you know, building a team and it's more than just money, right? It's networks and you all have a shared mission. Now, maybe different perceptions in terms of timeline of how you're going to achieve that value right or when but building a team. It's like any other team you're building, right? And you want to bring people on the team. That are a good fit for the type of company you're trying to build, but also bring additional value to the table. And it's not just about money. 

Jon - 00:12:30: Absolutely. And I think that's just like a great reminder that it is much more than just the money for sure. 

Chris - 00:12:36: Yeah, the members of my board are really great. Yes, they have put money on the line for sure, right? And so, you know, I have a responsibility to deliver on their investment. But they're very supportive, both in terms of the direction of the company. Also helping with staffing and things like that, helping me. So it's a great, great time right now.

Jon - 00:13:00: Yeah, absolutely. And I think too, something to just like keep in mind for anyone who's out there, like actively choosing investors or raising is just like you know, every company has its ups and downs. And like knowing how your investors will react when there's an inevitable down.

Chris - 00:13:18: Yeah. 

Jon - 00:13:19: Like that's critically important too. Absolutely. Because everyone can be your best friend when things are rosy.

Chris - 00:13:25: You learn a lot about people when things aren't going so well, right?

Jon - 00:13:27: Yeah, exactly. You will learn quickly. And how do people, just people generally, how do they handle stress? Because yeah, it can be not a pretty sight if you find out later that this person doesn't handle stress too 

Chris - 00:13:42: well. Yeah, and I think that's true of any relationship, right? Whether it's, you know. You're on a drug discovery team or your own team or your family, or. On the board. Getting to know people and how they react and think through things as well. I think building that rapport and that relationship and that trust. Really important before you, you know, jump with both feet in and embark on something. 

Jon - 00:14:06: Yeah, absolutely. And so now, you know, you're at transcripta and you're talking about building this machine and it's a culmination of all, I could see it. I can kind of see the pieces all together. Can you talk a little bit about I guess. What is the state of the market? And how does transcript disrupt the status quo, this machine that you guys are building?

Chris - 00:14:30: Yeah, you know, I come at it from the standpoint of well, why do we fail, right? Why do we only have a 4.1%% return on investment? And we largely fail because, well, the idea you thought you had the targeted hypothesis is wrong. Or you've run into some safety issue, but predominantly you've picked the wrong target. And there are ways to pick better targets, right? Human genetics is a great way to inform what are the right targets to go after. And the data would show and history would show that when you have human genetics on your side. More often than not, you will be much more successful than the industry average. So starting out... The monogenic rare diseases like That is precision medicine at scale, right? This is a hyper-rich arena, frankly, where the human genetics have told you thousands of times this gene causes that disease. And with small molecules and the ability to interrogate the transcriptome now, at scale, from a screening perspective, we measure drug response across 20,000 genes for every molecule we test in our lab. That's the transcriptome. And now you can start to intersect these two worlds bioinformatically and surface immediate opportunities where the causality, it's unequivocal. This is the cause of that disease. If I increase this gene expression, I'm likely to have a benefit if I decrease it or find a parallel. So we started there just because of the causality piece. And the tractability. But the other element of this is, well, how can we increase the speed to value creation? So I don't have to just start from de novo molecules, right, and start a project from a screen to an IND, spend $30 million per project. Yeah. Five to eight years. And that, you know, can be rewarding. But how can we go faster? Well, in the world of small molecules, right, there are, in fact, FDA approved drugs that still have commercial value to them, where if I could repurpose them into a new indication, I can create value very quickly. And then there's the next layer down. Well, there are molecules that have been in the phase two or phase three clinical trial. For which they have a human safety experience, they have drug-like properties, but they failed in their respective trial due to lack of efficacy, but they had an acceptable safety. Well, we're profiling those kinds of molecules because why? Well, when one of them hits, I now have something that already has a human safety experience, right, that I can take forward. And yes, we are also in that world of small molecules. Doing novel drug discovery so it's the combination of go where the causality is strongest, increase the speed to value creation. And then build something that you can do it over and over again, right? It's scalable and repeatable. And that would be a great thing to build, right? I think a valuable company. And where it fits in is as I alluded to, is you already have great companies that do drug lead optimization and clinical development really well, right? But where is there a shortage? Well, I think there's a shortage of really strong hypotheses that, again, that you can surface at scale repeatedly across virtually any therapeutic area. And that's what we are building. And that's where we fit in in kind of what I describe as like this pipeline foundry. Where the Drug-Gene Atlas that we're building, when we screen a collection of molecules that cover the druggable target space really well and fall into those categories of approved drugs and clinical stage molecules and high quality pros, but also novel molecules. And we intersect that with the transcriptome. And the transcriptome is this phenomenal thing that we know describes cell state and fate. It's the thing we look at when we understand health versus disease. We build diagnostic platforms off it. It is an immensely translatable currency, right? And it's also a great gateway to understand how existing drugs work because ultimately, I think most therapeutics ultimately work by modulating gene expression in some way. So it's directly tied to drug action, and it's a great way to discover new drugs. And we're going to the well where drugs continue to come from, which is the small molecule. And so it's got all of these, you know, common sense features to what we're building that I think will be highly extensible because we can look at individual genes in a monogenic setting. We can look at genes that encode for targets of high interest to the industry. So rather than developing a small molecule that inhibits the activity of a kinase directly. We can discover molecules that down-regulate the expression of the gene that encodes for that kinase and come up with a novel chemotype that is differentiated and likely has a different safety and tolerability profile. So we're actively doing that and we are finding these fast mover opportunities. And what we've also done is built this lab in a loop where we have a wet lab, we're generating all this insight. We just generated 400 million data points this summer, for example.

Jon - 00:19:26: Holy crap.

Chris - 00:19:29: And we're building drug gene atlases cell type by cell type. And now we have coupled that with training a machine learning system where we have trained machine learning models on individual genes, very robust, where we can now do a virtual screen of six and a half billion compounds over a weekend across all those models and predict novel structures, not inferring any type of mechanism up front, but simply inputting a structure and getting a prediction on that gene's expression. And we have now from that created new opportunities in areas like obesity and other CNS disorders, oncology. And so we now are creating, again, this foundry to me and using machine learning and AI to help support that. But a very active lab in a loop. And we are in discussions with multiple pharma companies about potential partnerships, both in terms of assets, as well as the platform itself and the data that we sit on. And my goal is, you know, the next two to three years to build this industry dominant Drug-Gene Atlas. That would allow us to not only directly discover opportunities from the data itself. But also predict activity of molecules in novel cell types that we haven't screened yet. Because we understand there is connectivity from one cell type to the next.

Jon - 00:20:50: So cool. I'm like geeking. That's so cool. My parents are not biologists. My mom was in finance and my dad was a structural engineer. So whenever I talk about like drug discovery and biology, they're like, oh yeah, it's like, it must be just like so super just like dialed in efficient, just like process. I'm like mom, dad, it's hard.

Jon - 00:21:14: I was like, this is mom, dad is not like that.

Chris - 00:21:18: It is hard, but it's also really hard, but it's, there's so many ways at which you can just, you're done, right? Like it's over. Like that project is over. And so to get even into the clinic and then make it through, and I certainly haven't myself been involved with it. You know, product being approved. But just to get to that, like, it is a miracle, frankly, I think in many cases that you get there. And I think people don't necessarily appreciate just how hard it is. And that's why we also need to tell people how hard it is. This isn't just we're not creating widgets, right? But there's a lot of excitement and the industry has created a lot of value for humanity over many, many decades. And clearly there's more to come.

Jon - 00:22:03: Yeah. And I think it gets back to what I see a theme of our conversations, like effective communications.

Chris - 00:22:09:  Yeah.

Jon - 00:22:10: Like I don't think us as like scientists do the best job necessarily conveying like this level of difficulty because like just having those conversations with my parents, there's like, yeah, it must be like a well-oiled machine. But I'm like the way I describe it, it's almost just like this brute force mechanism. At least it's getting better now, but it generally is this brute force mechanism and you don't even know, like it can just like exactly what you said at any given point just get completely derailed. And I love the transcriptors approach of like, how do we like de-risk this thing before we get too far along this plowed, like insert pens to hundreds of millions of dollars into this thing only to find out that that, it was dead to start. And yeah, and every, like exactly what you said, it's like a tiny little miracle that it actually goes the distance.

Chris - 00:23:03: Yeah, we have, you know, five different drugs that we've repurposed that are in, you know, small numbers of patients today. We have a burgeoning sort of later stage pipeline, if you will, of again, clinic molecules have already been in clinical development. That we have found new indications for. And then this generative approach, this AI-driven approach, is also really starting to make some hay and we'll continue to scale this both in terms of cell types the compute and the application and the other thing that's really cool is that at the same time you're uncovering therapeutic opportunities, you're also producing off-target data, you're producing selectivity data, you're producing biomarker data. All in parallel and simultaneously, whereas this has traditionally been a serial thing that's existed over many years. And so there's just the breadth of information that we capture. From every turn of the crank, if you will, from the data that we generate, because it's the transcriptome and what it represents is just immense. We're going to harness as much of that as we can.

Jon - 00:24:08: Yeah, that's exactly it. It's kind of like that sequential stop, go, stop, go, which is, I love that we can be actually just like way more efficient now and work things in parallel, like way more efficient.

Outro - 00:24:20: That's all for this episode of the The Biotech Startups podcast. We hope you enjoyed our discussion with Chris Moxham. Tune into part four of our conversation to learn more about his journey. If you enjoyed this episode, please subscribe, leave us a review and share it with your friends. Thanks for listening and we look forward to having you join us again on the The Biotech Startups podcast for part four of Chris's story. The The Biotech Startups podcast is produced by Excedr. Don't want to miss an episode? Search for the 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, https://www.excedr.com. On behalf of the team here at Excedr, thanks for listening. The 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.