Dr. Kate Yen: Scaling a Biotech, Running Lean, & Utilizing Translational Biology (Part 2)

Intro - 00:00:01: Welcome to The Biotech Startups Podcast by Excedr. Join us as we speak with first-time founders, serial entrepreneurs, and experienced investors about the challenges and triumphs of running a biotech startup from pre-seed to IPO with your host, Jon Chee. In our last episode, we spoke with Kate Yen about her passion for science, her transition from academia to industry, and to the key experiences that shaped her approach to drug discovery. If you missed it, be sure to go back and listen to part one. In part two, Kate takes us through her leadership journey at Agios, where she played a pivotal role in advancing a novel cancer therapy through clinical trials. We'll hear about the challenges of taking a drug from discovery to FDA approval, what it's like to navigate the biotech startup landscape, and how she built Auron Therapeutics from the ground up. She also shares insights on managing lean operations, foraging strategic partnerships with big pharma, and the importance of grit in biotech entrepreneurship. Without further ado, let's dive into part two of The Biotech Startups Podcast. 

Jon - 00:01:21: And, you know, from there, I know you're kind of promoted to director of biology. How did your kind of responsibilities change when you transitioned to that role? 

Kate - 00:01:32: Yeah. So, I mean, that was really leading more of a function when I was doing the in vivo stuff and, you know, applying to multiple projects and, you know, helping out from multiple projects. Whereas when I went in and led the IDH team, that was really focused specifically only on that one program. And really, what are the biomarkers and the mechanism of how that mutant gene is driving cancer and how we're going to be able to track that in the clinic. You know, we had been developing a drug. We had a whole team that was doing the drug discovery to develop small molecules against that mutation. But you can have the best drug in the world, but if you don't know how to use it, it's not going to help you, right? And so, you know, the mechanism is what we needed to understand. And that was what my job was. And I, again, it was probably the experience of a lifetime. I got to understand a target from early discovery of the gene and, okay, it's playing a role in cancer and what that gene initially, we knew what it did. And then really digging deep and really getting a firm mechanistic understanding of how that mutation is really contributing overall to cancer. And then going into the clinic and getting drugs approved off of that. So I got to see and lead a program from target identification all the way through phase three approvals of drugs for patients. And that is, was my dream job, right? To take something from basic science to translation. And I got to meet patients that took the drug. It was like unbelievably moving and so exciting. And you really can't recreate that event. But again, I think I've just was at the right place at the right time. And the exciting science that came along with it really was what motivated me to keep going. 

Jon - 00:03:25: That's so cool. And again, kind of similar when you're at Merck, you're just like a rare opportunity to just be the sponge. And then now you're like leading the thing. Can you talk a little bit about like, I'm going to imagine now that you're leading this, you are the one managing these kind of diverse avengers consortium. How did you approach that management and leadership, you know, role again, keeping them like, you know, a very diverse group of people all rowing in the same direction? Kate - 00:03:53: So myself and this other woman who is a chemist, she and I ran the program together. And, you know, I think both of us have a very similar work style. It's like no nonsense. Like this is what we need to get done. How are we going to get this done? Let's work through it together. And just being very transparent and communicative with everybody. And like, again, like I don't want to torture people. I have empathy. We'll have things that come up and down and, you know, people know things and don't know things. You know, if they don't know things, it's okay. Let's find out the answer. And so, you know, really just, you know, imparting all of that wisdom that I'd gotten through my training and my career and using that to, you know, bring people together so that we could drive the program forward. 

Jon - 00:04:38: Very cool. And so, you know, we touched on the kind of the in vivo portion of the kind of the cycle. Can you talk a little bit about getting into the clinic? Like that's another deep end, probably the deepest of deep ends. Kate - 00:04:50: Yes. 

Jon - 00:04:51: How did you learn the ropes there? Kate - 00:04:52: Yeah. So as we were moving into the clinic, myself and my team were the ones who understood the deep biology of the program. And so when we were writing the Phase One protocols for the trial and the exploratory endpoints and the biomarker endpoints that we were going to be collecting, they wanted me and my team to really have input into that because they wanted to be able to understand very quickly, is the drug working in patients? And so that's how I got sort of pulled in as a clinical scientist into following the drug. And David, I think, Schenkein, the CEO at the time, he is a big proponent of taking someone and making sure the science follows the drug into the clinic. So it doesn't go over a wall, over a cliff, and then the rest of the scientists never see it again. It becomes a clinical asset and it's, you know, never the twain shall meet again. That's not how he likes to operate. And I agree with him. And Sam. Sam Agresta, who was running the trials, brought me along and I got to learn all of the pieces of how a clinical trials run. And that was like another whole learning experience. That was completely crazy. I didn't see any of that at Merck, though, even though that's happening. You were too siloed to ever be part of that team. So, again, I got to see the build of a clinical organization and then I got to be part of it, which was really, really exciting. 

Jon - 00:06:16: That's so cool. And I guess, quick question, how common is it to just toss it over the wall? Is that the status quo? It's literally just, all right, here we go, clinical team. Kate - 00:06:25: Yeah, in big pharma, it does happen that way. They often just, they turn it over to a translational team where it becomes much more biomarker and like assay development as opposed to the mechanism studies. In biotech, it's not as much because they just don't have the resources to have a whole group. You kind of have to do both, but it's more common than you think. And so I have been very purposeful in, or I and my company now, what we call biology. From day one, it's translational biology. We don't call it discovery biology. It's translational biology from day one. Because I think that the biology, as I said, always runs. It's preclinical and clinical, but it always runs along the drug discovery aspect in parallel. And it needs to continue as you get into the clinic. And you want the team of people that understand the biology the best to be informing the physicians about how to use the drug. 

Jon - 00:07:19: It makes a lot of sense. Like it makes a ton of sense. Um, you know, intuitively it's just like, yeah. Like why would someone who has this is their baby for many, many years only to just like, here you go. Someone who has- Kate - 00:07:34: No idea. 

Jon - 00:07:34: No idea. Yeah. Good luck. You're just like, good luck. It just doesn't, that, that aspect is like, huh. It's like kind of, you know, why? And you know, as you were having this baptism of fire in phase one to phase three, can you talk a little bit about what were some like challenges and triumphs as you're working through the clinic? Kate - 00:07:53: Yeah, I mean, I think one of the challenges is, well, I mean, the drug works by a different mechanism than most cancer drugs that are being developed. Most cancer drugs cause or trying to kill cancer cells. And, you know, obviously you want to, you know, shrink someone's tumor. But this mechanism against IDH inhibitors, it actually causes tumor cells to terminally differentiate. So most tumor cells are more in a XTM state, and then you treat them, and then you actually promote differentiation of those cells out of that XTM state into a mature state, and then they stop dividing and proliferating. And that mechanism has been, had been at the time proven to work from a different form of leukemia, but it had never really been proven to work in the context of solid tumors. And so we had to really understand that biology and build assays and biomarkers and experiments so that we could prove that that was how it was working in the clinic. And so we had to teach the physicians about what they were looking at. And we also had to talk with the FDA and really work hand in hand with them about the mechanism to help us move those drugs through the development process. 

Jon - 00:09:12: So what I'm hearing is that you did the clinic on hard mode, like ultra hard mode, where there was a minimal precedent. Let's do this from scratch, where we need to get you up to speed, regulator and physicians of this different approach. That's incredible. And for anyone who's out there, maybe this is their first go, getting into the clinic. What are some common pitfalls to avoid? Kate - 00:09:40: I think often people just think they know what they're doing and they put together protocols and they don't partner with the FDA. I think David was a big proponent and I, that way at my company, a big proponent of, you know, having interactions with the FDA, telling them what you're doing, talking to them, getting their advice about how to, you know, go about setting up the trials in the most efficient manner. And I think that's one big important aspect. And the other is thinking about biomarkers and, and exploratory endpoints that you can build into the trial so that you can actually track the biology. 

Jon - 00:10:16: And it makes a lot of sense. And if I think of it from like first principles, like the FDA wants to make this thing work. Kate - 00:10:22: Yeah. No one has any reason to make it fail. 

Jon - 00:10:25: Yeah. Yeah. They don't want, like, they don't want to fail you. So it's like, yeah, like that makes like rational sense. They're in the same boat, even though they are kind of like the gatekeeper of it all, but they are. They want you to get through it if you can, which makes a lot of sense. And it sounds overly simplistic when I say it, but it's like, you know, obviously it's a very complex endeavor. Kate - 00:10:47: Yeah, I mean, their gatekeeping is to make sure that it's safe, right? They don't want to hurt anybody in the process of testing something. And in order to be able to show that you have benefit and not hurt somebody, you have to understand the biology. And so working in partnership with them to safeguard against all of those aspects is the best path forward, I think. 

Jon - 00:11:11: Absolutely. And, you know, you talk about like learning the business side while you're at Adios. Can you talk about how do you keep it within budget? Because all I hear now is that clinical trials are ungodly sums of money and are never run on budget. How do you keep it within budget? Kate - 00:11:28: Yeah, I mean, I think that is very challenging. But clinical trials are super expensive. Yeah, you just have to think smart and have interesting and smart designs. And again, I mean, I hate to harp on it, but if you understand the biology as you go in and you build assays so that you can see, is it really working? You can tell quickly if the drug is working or not. And biomarkers and patient stratification and understanding what types of patients you need to start with your drug, that tells you if it's going to have legs or not. And, you know, you can make decisions quickly if it's not worthwhile to keep pursuing or if it means you want to actually spend more money and go faster. And those are decisions that you need something to guide you along the way. And the science is what does that. 

Jon - 00:12:20: I'm frankly really jealous that you had this opportunity to do this. As I'm hearing it, I'm like, dang, if I was it could be a fly on the wall and just like see all this all the way through. Because I think it's a really rare opportunity. And I haven't heard many stories like this where you can go from soup to nuts. And I guess question about when you were there, I believe you guys IPO during your tenure there. Kate - 00:12:43: Yes. 

Jon - 00:12:44: How was that transition from private company to publicly traded company? Kate - 00:12:49: It wasn't as visible to me that transition from a business perspective. We were kind of sheltered from that, I'm sure, from understanding what that means now. The leadership team was like, ah. 

Jon - 00:13:01: Yeah, yeah. They did a good job, it sounds like then, if they were able to keep their hair on fire, but you guys were like, this is fine. Kate - 00:13:08: Yeah, I mean, I think the biggest thing is like, you know, we just had to be very careful about what we were saying and, you know, clinical data, making sure someone didn't slip and say something that they couldn't say. And, but, you know, they kept a good handle on it and they ran it well. I know it must've been challenging for them, but I didn't feel it quite as much. 

Jon - 00:13:27: Yeah, yeah, yeah, totally, totally. And, you know, as you're wrapping up your time there, when did you know it was time to leave? And when did you know it was like, you are gonna do your own entrepreneurial venture? Kate - 00:13:39: So this is a fun story. You know, I was in the Phase One trials and we got our drugs approved on the Phase One data, which was super exciting. And then I was in the clinical group and I was now leading the global phase three trial for full approval. And David, the CEO of Schenkein came up to me and he said, 

Jon, what are you doing? He's like, you can't run phase three trials anymore. Like this isn't like your sweet spot. And these three trials are very operational and big, you know. You know, but I got to learn all of clinical development, all the aspects that go into clinical development and how you write a trial and the bio-stats and the operations and all of that piece. And I said, well, I don't know. And I was truly looking at that point to try and figure out. And I was very intrigued by the science of promoting differentiation to enable therapies for cancer and then to go about it differently than the standard cytotoxic approach. But I couldn't find any companies that were doing that, um, research and I was looking and David said to me, being David, he said, well, why don't you just start your own company? And I- 

Jon - 00:14:46: It didn't matter like that? Kate - 00:14:47: Yeah, he is pretty much like that. I thought he was completely crazy. I was like, what are you talking about? Like, it just seems so foreign. And then he said, no, I'm serious. You should think about it. And I kind of noodled about it and he was noodling in the back of my head for a while. And, you know, I started to think a little bit, well, what would I do and how would I put this together? And I started to talk to him a little bit about it. And then I kind of built out a little bit. I talked to some friends. I talked, built out a little bit of a business idea. And then David connected me to WilmerHale of the corporate attorneys and they incorporated me. And I don't know, from since that, I've just been putting one foot in front of the other. And here we are today. 

Jon - 00:15:28: That's amazing. And like, again, it's kind of like, well, it's what we're talking about. It's like, we're all just figuring it out and just like a day at a time. That's like really what it is. Kate - 00:15:37: Yeah. 

Jon - 00:15:38: So now you're officially incorporated. I guess the first, you know, your co-founders, your early days, your early team. How did you guys come together? Kate - 00:15:47: Yeah. So my three co-founders, so Matt Vander Heiden, Ross Levin, and Eytan Stein, I worked with all three of them at Agios on the IDH development. And so they were also, you know, physician scientists who understand that, you know, mechanism. Is it really cool? And I wanted to build a company. I said, would you be willing to come with me and do this? And they're like, sure, let's try. If you can do it, like go for it. So we incorporated with them as the co-founders. I had nothing. It was just me and my kitchen. And I went out to friends and family and I shared them with my idea about what I wanted to do. And I raised about a million and a half dollars from friends and family to get some initial science going. And I hired Laura Antipov, who has been with me since the beginning as a consultant initially. And she and I basically took that money and started to do some experiments at CROs. I knew how to work through CROs. I knew how to do collaborations with labs. So I found labs that might be interested in working with us. And we also did a collaboration with a company that does a lot of computational biology. And so with them, we just kind of started to build a little bit of momentum around some initial targets that we wanted to study. And from there, we've expanded the company. I was able to convince proper venture capitalists that we actually had built something. And we did our first seed financing with venture in December of 2020. 

Jon - 00:17:21: That's so cool to hear that origin story, because I think especially being in like the San Francisco Bay Area, where it's like there's like venture capital just like overflowing out of this area. And there's like a very kind of like prescriptive way of like, this is how you run a biotech company. Kate - 00:17:39: Yes. 

Jon - 00:17:40: Here's the playbook. Here's how you finance it. Here's who you hire. It's kind of like very, whereas I love to hear that it was just like for you, that you raised the friends and family round and you ran it lean, like that you can run it lean and not have to do like the kind of the standard playbook, which is refreshing to hear. Kate - 00:17:57: Yeah, the venture capitalists, when I was first pitching to them, they kind of looked at me like I had three heads. They were like, what? What are you doing? 

Jon - 00:18:04: Yeah. I love that. Because I think it's kind of that out-of-the-box thinking. And also, it sounds like every experience, everything I'm hearing was kind of like a creative. You were just like, I know how to do this. I know how to. And you had all these puzzle pieces, and you stitched it together. So I love to hear that. And the humble beginnings, it's like you're in your kitchen. It really is like that. It really is. Because I remember when I was first starting Excedr, I was at a dining room table. Kate - 00:18:36: Exactly. 

Jon - 00:18:36: I was just like at a dining room table. I was like, all right, I'm going to figure this out. I'm just like, figure this thing out. And so, you know, when you were just like doing the external collaborations and working with CROs, was there a point in time where you're like, we need to, you know, bring things in-house? Was that around like when the venture capital came in? Or are you guys still running super lean in that way? Kate - 00:18:56: Yeah, no, we've been running very lean. We didn't start our own labs until about maybe a little over two years ago, maybe just two years ago. We ran through all the different CROs, and I think it's a lot easier now. I mean, the CROs are pretty well established, and there's CROs all over the place that you can gain access to. And we started to hire people in that could manage the CROs to do the work we needed to. So I'm a biologist by training, obviously, and then I hired as a CSO a chemist. So Dave joined us, and he's got a lot of it, tons of experience developing drugs. And I think between Dave and myself, like, we synergize with each other in our expertise, right? And so that is really a great way to kind of push things forward. We build out the biology and very lean chemistry teams, and we use CROs to, um, really keep the cost down as much as possible. And then when we wanted to do more bespoke, you know, tailored experiments, that's when we got some labs. But we didn't go and hire or find a lab space that has 30,000 square feet and offices and build the whole thing. We actually worked through a co-op lab shares, which is really great. And, you know, I don't have to pay overhead for all the instruments. I don't have to pay for a lab manager. I don't have to deal with all that. We have a few benches and our equipment, that we need. But then we just share the space and we have kept it as lean as humanly possible. 

Jon - 00:20:31: I absolutely love that. Like, I love that because I think I was talking about the kind of like the prescriptive nature of like how to run a biotech. It's like it brings down the activation energy. Kate - 00:20:41: Yes. Yes. 

Jon - 00:20:42: Right. There's like great like there's great science to be had and to be to come to come to life. And you don't need to have this blockbuster check to even get started. Kate - 00:20:54: No, you don't. You don't. 

Jon - 00:20:56: My wife's in software and like, obviously software is a capital light and the very iterative, but like your approach sounds a little bit like about how, like, you know, everything that Y Combinator talks about, just like test it, keep it lean, keep the overhead, like as low as possible. So you can stay nimble and not have this massive lease that you like, what am I gonna do with all this space? I like, I know I'm like stuck with this. Kate - 00:21:21: Yeah. And I think that comes back to sort of my empathy and that how my guiding principles of, you know, I don't want to hire 70 people that I need to lay off because things can go well, right? And I also don't think you need a ton of people to do this. You need the right people to do it. And you need the right team and the right environment to come together and be willing to be entrepreneurial, vulnerable, excited, push forward, all of those things. And I want to, I want to just utilize that synergy rather than wasting money on things. I put it to your point, put it to use and put it to fund the science so that you can actually move quick. 

Jon - 00:22:03: Absolutely. And I think it's super painful to see in the news where there's like more layoffs, more layoffs, more layoffs, more layoffs. And you're like, you know, it's like, those are people like who have like, families and like bills to pay. And I always ask myself, like, there's got to be like a more sustainable way to do this. Like, does it really have to be like, where it's just like, you know, just kind of like boom bust. Can we like, can we do it? Whereas it's like exactly what you said, like kind of like more like piece by piece, like bring in the right people, not just necessarily like hiring for like a vanity headcount. Kate - 00:22:36: Yeah, exactly. I mean, I always see that everybody's like, oh, you know, you hired this or that, or you're brought in this check size. And I'm like, okay, it's kind of noise to me. I just, okay, I got to get these experiments done. I don't keep pushing forward to get to the clinic. 

Jon - 00:22:50: Absolutely. That's, and I couldn't agree more. And it sounds like you have your core team, your co-founders, you have your kind of like, okay, we, we have these kind of the stakeholders in place. Maybe let's talk about the market first and how does Auron, your technology and approach disrupt the status quo out there in the market? Kate - 00:23:09: Yeah. So the company was founded on the principle that cancer, we focus initially on cancer, but that cancer cells are hijacking normal developmental biology pathways in order to promote tumorigenesis. And to me, it's always been frustrating when you want to try and figure out why a cancer cell is a cancer cell. People tend to take one cancer cell from one cell line and compare it to another cancer cell that's a cancer cell, different genetic mutation, and then they figure out what's different. And then they try to build biology on that. And to me, I'm like, I don't understand that. You want to compare to normal, right? Not another weird cancer cell. 

Jon - 00:23:49: Yeah. Yeah. Yeah. Makes sense. Kate - 00:23:54: Right. And so we have spent time to build this platform that we have built an Atlas of normal human development, a single cell Atlas of normal development that starts from very early XTM cells all the way through terminally differentiated cell states. And that Atlas, we use it as a reference and we can map tumor cells to it and understand exactly where they're blocked in the differentiation cascade. And then once they're mapped, we can do the computational comparison between tumor and a normal cell state matched normal tissue. And then we can have a clear understanding of what pathways are disrupted in the tumor, what developmental pathways are being hijacked by the tumor compared to the normal cells, and then target those to push differentiation and generate novel therapies. And so that's what we've done. I think, you know, it's a little bit, a different approach than most people take. But the technology and the single-cell RNA-seq and omic analyses and AI and machine learning tools that have become available now lately, we've really capitalized. And so I think the sweet sauce of our company is that platform that we've built, but it's really that interface between computational machine learning, biology, and molecular biology, basic biology that is coming together to really advance programs. And now it's really exciting, our lead program that we're taking into the clinic. There's lots of data now that's supporting all disease areas, multiple disease areas are hijacking developmental biology pathways. It's not just cancer. And so there's an utility to potentially use this platform much more broadly than oncology. 

Jon - 00:25:39: So cool. And I guess like question on AI/ML in biology, I know there's like a lot of talk about it. And you have your hands on it. Like, do you see in your like day to day where there's like, oh, this is like AI/ML really moving the needle? Or is it more of just like, you know, what is almost overly grandiose in its promises? Kate - 00:26:01: Yeah, I mean, I think people use it as a buzzword all the time. And, you know, fine if you need to say what you need to say. But like we are actively using it because, you know, these large omic data sets, they're just too big to process. Right. You can't do it by yourself. Right. And so we we have our computational team that really reduces it to practice. And so we use these large omic data sets and we've mapped we've used it to make this Atlas. And then we've developed specific machine learning algorithms that allow us to map the tumors to the Atlas. And then other machine learning algorithms that allow us to define what genes are driving the differential expression between the tumor and normal. And so we have a very specific application. We're not trying to apply AI machine learning to everything. We're really asking a very specific question as how developmental biology pathways are being co-opted by disease. And then we apply machine learning technology to answer that question. 

Jon - 00:27:06: Very cool. Yeah. I, you know, every time I'm like on like the internet, I'm just like, and here, too, like you couldn't go a block without overhearing like the promises of AI. And I'm like, I was like getting coffee. I was like- Kate - 00:27:19: Yes. 

Jon - 00:27:20: This is, where am I? I was just trying to get a coffee. But there's like three different like AI/ML conversations like going on, like what is real and what is it? Kate - 00:27:29: Yes. 

Jon - 00:27:30: And for me, I can't. I'm sure, you know, AI/ML can be used in a bunch of different applications. But what I care most about is like, does it actually move the needle? Kate - 00:27:38: Yes. 

Jon - 00:27:39: In like, you know, life science. And I'd love to hear that you're like, yes, like for your case, it is, which is awesome to hear. Kate - 00:27:46: Yeah. 

Jon - 00:27:47: And so you talked about your origin platform. You talked about your pipeline development. And I know when it comes to business models, you're either bucketed into platform company or you're developing this candidate to push through into the clinic in your pipeline. And it seems like you're doing both. And can you talk a little bit about, in years past, their platforms were all the rage. And then now it feels like it's kind of shifted in the other direction. Kate - 00:28:13: It's not all the rage, yeah. 

Jon - 00:28:14: Yeah, it's not all the rage anymore. 

Kate - 00:28:15: Yes, yeah. 

Jon - 00:28:16: Can you talk a little about why does it oscillate? And honestly, what's their opinions on both approaches? 

Kate - 00:28:22: Yeah, I think it oscillates a little bit around the markets, right? I think platforms are kind of big and visionary, right? And, oh, we can do everything with them. And, you know, at the end of the day, you need to get a return for your investment, which is being able to sell a drug, right? And so that's why you need the pipeline and you get it into the clinic and you can get it approved and move forward. So I think the markets being what they are today and investors are looking for sure bets that they have something that is moving along and can get them to that return in their investment. When things are flowing and money is flowing, I think people are more willing to take a lot more risk and be creative about what the platforms are. Again, I think I'm not trying to blow smoke with people about our platform. I've just built this tool to help me understand the biology so that we can move it into making a drug. Because I, too, want to get to a drug for the return on investment, yes, but really, ultimately for patients, right? I want to provide better therapies. Like, I'm tired of seeing people and friends and family and hearing awful stories about people taking rat poison. And it's just terrible, right? And there has to be a better way to do this. And so I think you need both. I think the platform should set as the core of your company and sort of what you're doing. But, at the end of the day, you want to make something that is marketable for patients and for investors. 

Jon - 00:29:55: Absolutely. And yeah, it's kind of this thing where if it can just be the thing that is generating your candidates, awesome. I guess that's a question for you. Now you're talking about how this Atlas can be applied outside of oncology. Does that mean are you looking to expand outside of oncology? Or is it something where the platform, you're going to be opening it up to external collaboration as well? 

Kate - 00:30:19: Yeah, so we are actually looking to expand outside of oncology. Our lead asset, there is potential opportunity for that outside of oncology, and we're actively exploring that right now. I do think it also opens up potential partnership collaborations with pharma, and we're talking to pharma partners about that as well. Our platform could be useful to them for disease areas that they're interested in and thinking about approaching, can we help them think about good targets or better biomarkers and using our platform to do that? We're totally open for that. And I think there's lots of different opportunity to grow the platform as well. We're small and nimble. We're trying to stay focused. Oncology is our bread and butter right now, but we are actually actively exploring inflammation and autoimmune disease right now. And those two biologies are also very linked with each other in cancer, there's inflammation that causes cancer, cancer that can affect inflammation status too. And so it's not a big leap to think that there'd be synergies there. 

Jon - 00:31:29: Absolutely. And when it comes to working with pharma partners on utilizing your platform, I'm thinking about it like you navigated the academic part collaboration. You navigated the CRO collaboration. Now in comes a new entrance, big pharma. How's that? Like, how did you build that muscle? Kate - 00:31:51: Yeah. So that goes back to Agios days. So when we first, you know, we did the initial financing, the $30 million that they raised through venture, but then we got a partnership with Celgene. And so I worked with Celgene both on the research side, you know, for the lead program, I was the one going in front of all their committees and things, telling them the science, because, you know, we had a financial partnership with them. And then when we got into the clinic, I was also working with them as we were developing, co-developing the drugs. So I got a lot of experience in that aspect. And then also reaching back to my days at Merck, I saw that as well, you know, so I know how pharma works. So that also, to your point earlier, you kind of figure out what the other people need, what they're trying to get at, and you know what you need and how can you work together. And, you know, big pharma and biotech have a lot of overlapping, end game that they want to get to. They have different ways of doing it and individual needs, but there's a lot of ways that they can synergize and work well together. You just got to get the lawyers out of the way. 

Jon - 00:32:58: Yeah, yeah, yeah, yeah. You know, that's for sure. Can you talk a little bit about like, what is the unique individual need of big pharma when you're entering that like conversation? Like what is it that they're optimizing for? Obviously there's commonalities, but like, what is the differentiating like priority for them? Kate - 00:33:16: They're much more conservative, I would say, than biotech, because you're kind of flying by the seat of your pants. So, you have to kind of manage that. And they can be conservative because they have the money to do things conservatively. Whereas I think biotech, you have to be scrappy. And how to navigate that can sometimes be challenging. 

Jon - 00:33:40: Absolutely. And I'm going to imagine there's probably a ton of like stakeholders that you have to socialize. Kate - 00:33:48: It's a whole different approval process that you have to get through, for sure. That is a big problem. 

Jon - 00:33:54: And so, like, you know, I'm just very curious. If you're trying to secure this partnership to utilize the Origin platform, who's, like, the first person you reach out to, like, at, like, big pharma? Is there a specific person? And then, I guess, curiously, like, who else do you need to bring into the conversation? Kate - 00:34:11: So that, I think, you know, as I've learned along the way, you actually need to reach out to the scientists. You need access to the scientists. You need to get an internal champion of the science and your approach and what you're doing to be the person fighting for you internal to the big organization. The business people that layer on top, they're not scientists. They can't say is this going to be a good business opportunity or not. They can take that recommendation from the scientists, the science team. So I think you really need to find that internal champion and really foster those relationships and show them all the opportunity that you bring forward and then have them be the ones fighting for you with the business team. 

Jon - 00:34:57: That makes a lot of sense. It's like, who knows the intricacies and the inner workings better than the person who's at the bench? Like, who knows this? 

Kate - 00:35:05: Exactly. 

Jon - 00:35:06: That makes total sense. And as you're like thinking about company building for Auron, it sounds like you guys are like slow and steady wins the race kind of. And we touched on it kind of already, kind of like what are the cultural North stars, but what is the cultural North star for you guys at Auron? And like any tips on like hiring and retaining great talent? Kate - 00:35:27: I think for me, being transparent with the company, everybody's kind of working together. If I had my druthers in the world, I wouldn't have a hierarchy in titles. It would just sort of be everybody, you know, everybody has their expertise and their value at, and you kind of put everybody together and push forward. And I think people like that. I like that. I think I learned the most when you kind of explain the rationale of the business behind why you're making decisions that you're doing so that people don't feel like they're being whipsawed and they understand it and then they're not so angry about why you're doing, oh, I get it now, why you have to make that choice, you know. You know, obviously you can't tell everybody everything, but, you know, within reason, I think it brings stability and people like that. They learn. That's how I learned at Adios. I got to see it and it taught me all the things that I've learned and helped me build this company. And hopefully that is something that people who work at Auron can take forward. And their career as they develop.

Jon - 00:36:26: Absolutely. It's kind of like the why behind the what and like, and it's like important to and I think too, it's kind of like, for me, I very much like have a similar like approach and that transparency. It's like, we're all adults here. Like, sometimes it's hard. Like, this is a hard problem that I am struggling with. And they can handle it. You don't need to patronize them. And like, you know, they can handle it. And I think that helps. Like, because when you're when you leave anyone in the dark, it's like, that's where the kind of anxiety starts brewing. Kate - 00:36:57: Imaginations run wild. 

Jon - 00:36:58: Run wild. You can't you can't stop that. So the only way like you got to just like be forthcoming about whatever it is, insert like thing that you want to be talking about. So I definitely agree with that. And, you know, as you're building this company, it sounds like, you know, you secure that first institutional round of capital after kind of doing the more lean and mean kind of like proof of concepts. What's your philosophy on fundraising? I know the past few years has been tough. Like, it's been tough. How did you navigate that? And like any unconventional tips for anyone out there that is hitting the fundraising road? Kate - 00:37:32: Yeah, I think it is definitely tough out there right now. I think, you know, we feel like we're constantly fundraising, but it's just the nature of the beast at the moment. But I think for us, our North Star is just if you do good science, I think the rest will come behind you. And so we make tough decisions. We look at things. We don't just keep going down rabbit holes. If it's not working, it's not working. Move on. And like, you know, if it's working, keep going. Right. And again, being transparent with the board and sort of showing them the progress that we're making. And we've just kept that North Star of do good science and the rest will build itself around you. 

Jon - 00:38:12: Absolutely. And I guess I have like two follow up questions to that. You mentioned the board, like, you know, being the CEO, you're probably interfacing with the board a lot. How do you effectively design your board and how do you run a effective board meeting? I have my approach, but I have a very small board. And, you know, I think a lot of founders out there just like. Don't know what they're like. It's a, it's a, it's a learned skill. Kate - 00:38:35: Yeah, and I'm learning it. Like, look, I got to this place. I didn't come from being in boardrooms. I'm learning that as I go. And I'm fortunate enough to have a team of people around me that are willing to help me and help me progress and grow as a CEO. And I think the trust that I built with them is through being able to do the science, keep the budget under control, keep them informed, get their opinions, being able to raise capital in this tough environment, even if it's not, you know, the gazillions of dollars that some people bring in, you know, it's what we need to keep moving forward. And I think we meet our goals. And if we're not, we talk. But I think what we set out to do when I did my first seed financing, we have done. And I'm proud of that. I'm proud of the team. And I'm very grateful to, the support that the board has given me. 

Jon - 00:39:33: Absolutely. And I think something that stood out to me as you were describing that is like, It's okay to also to your board to say when it's like something isn't working. Kate - 00:39:42: Exactly. 

Jon - 00:39:43: It's more scary. It's a scarier conversation. But at least I think I've had, I think about my board meetings that were most kind of productive have been words like, let's problem solve here. I'm not going to sugarcoat it. This is like tough. Kate - 00:39:56: Yeah, yeah. This is, yeah. Yeah. And I think once someone has told me, you never want to surprise your board with anything. And I think that's good advice. 

Jon - 00:40:05: Yeah, yeah, yeah. That is great advice. Like, do not, do not. And, you know, when it comes to, you know, your fundraising experience and journey, how... How do you approach like investor like selection? How did you choose the folks to be in your corner? Kate - 00:40:20: A lot of it is through connections and who people know and their networks, right? And so when we go out and fundraise, a lot of it's members that the board have, you know, brought forward that they know in different funds, people that they like to co-invest with through, you know, some academic folks too. We gain access to financing. We have a IR firm that we use that helps as well. Bankers, they help too. So we tap into all the different channels. I mean, it is definitely hard right now. I think a lot, it's just a crazy market and hopefully things will turn. But, you know, I think you just can't get discouraged. You just have to keep going. And when I feel discouraged or, you know, frustrated or, you know, tired, I just keep thinking like, okay, the science is really real here. I'm really excited by this. We have something. We just have to keep pushing. And we do. And again, like the true North Star of all of this is that I... I want to make better drugs for patients. I want to try and find things that are not making people deathly ill and, you know, giving you, you know, incremental changes in your quality of life or length of life. It means this is something, it's a nut we can crack if we figure out how to do it together. 

Jon - 00:41:36: Absolutely. And I think a couple of things that, you know, directions is that it's like this aspect is just like it's not sexy. It's just grit. It is just like you have to be gritty, like super gritty. And, you know, with your North Star of thinking about the patients, it makes that grit. It comes from within. It kind of like you get out of bed and you're like, I'm not going to quit. Because if you don't have that North Star, it's like pretty easy to just like throw in the towel. Kate - 00:42:04: Yeah. 

Jon - 00:42:04: Screw it. I'm too tired. I'm like, but I love how like that is like the guiding factor there. And also, too, it comes back to like knowing people like. Kate - 00:42:16: Yeah. Using the network. Use the network because that's that. I can't. My kids, my son, I told you he's about to graduate college. And I think they're learning that this is how life works. Right. It's like I said, you can go to the fanciest schools and be wherever. But that helps for sure. But help. But why does it help? Because it helps, you know, build your network. 

Jon - 00:42:38: Yep. Absolutely. 

Kate - 00:42:40: And so you just have to capitalize on all of this. 

Jon - 00:42:42: Yeah. And I think, too, about like the one thing that I think as a scientist, when I was like first learning, I was like. Ew, networking is kind of icky. Like, but you can do it in a not icky way. Yeah, exactly. You can definitely just like, and it's more of just like, I always think about it as like a, it's like a friendship. Kate - 00:43:01: Yeah, exactly. 

Jon - 00:43:02: Making friends. Make friends and be authentically curious and interested. And that's ultimately what I think, or at least my kind of approach to making connections with people. Just be curious. And even when you talked about your lab experience and your PI coming on to the SAP. Yeah. It's just like, you just had a great working relationship. I'm sure like a friendship too. And it's phone a friend. Kate - 00:43:29: Yeah. 

Jon - 00:43:31: You want to be able to like phone that friend and like, and you want them to be able to pick up and you know, if you like have an authentic friendship that they're going to pick up the phone and, you know, the phone and, and, you know, make that, make that do that back channel, like co-sign up. But as we're looking forward one year, two years, what's in store for you and Auron? Kate - 00:43:52: Yeah. Well, we're about to enter the clinic with our first molecule. So in the next, you know, couple of months, which is super exciting. And, you know, I think I'm really excited to show proof of concept of this whole hypothesis that, you know, what we've done is really a way to treat cancer. So that's the data that we'll be generating over the next year, 18 months. And then I think really exciting to think about how to expand outside of oncology again, and really tapping into this platform and this type of biology and see how we might have effects other places as well. And so, you know, I hope we are able to move quickly and really bring in, you know, the team and the people and provide good drugs for patients. 

Jon - 00:44:42: That's amazing. I'm pumped for you guys. Like super pumped. Something that you said that really stood out to me. It was just like, we're not just trying to just do like these incremental improvements. Lack of a better phrase is like, go big or go home. 

Kate - 00:44:55: Yeah, exactly. Yeah. 

Jon - 00:44:56: It's like, what are we doing this for? Kate - 00:44:58: Yeah, you do. That's the grit, you know, and you just put your ego aside and one foot in front of the other and keep moving forward. And you have to think about, I mean, we've been doing drug discovery and cancer research for many, many, many, many years. And people have been targeting the same things over and over and over again, just different modalities, but it's not moving the needle. And so, you know, you can bang your head against the wall over and over again, but it's, you know, at some point you got to just kind of, all right, let's try a different path. And it may not be right, but at least it's another shot. And I actually think it's not to say that the paths that have been forged are wrong. I think there's a potential to synergize with interesting other avenues as well. So, you know, cancer is a very complex disease and you need to attack it from multiple fronts. And so this is just one other front that we're starting to chart forward. And I look forward to it. I look forward to getting that in to the clinic and then thinking about how we can work together with other therapies and get better improvements and better lives for patients.

Jon - 00:46:03: That's amazing. Kate, you've been so generous with your time. I'm having a blast. Like I could keep going, but I realized I should not be taken over your whole Friday, but thank you. You know, I've learned a lot. I'm having a blast. And in traditional closing fashion, we have two questions. First question is, would you like to give any shadows to anyone that supported you, you know, throughout your career? 

Kate - 00:46:25: Well, I think I have many people to thank for my career. I think Mike Carey for my PhD, Charles Sawyers for my postdoc, and David Schenkein from my work at Agios. I think all of them have been really true mentors to me as I've moved through my career. 

Jon - 00:46:42: Awesome. And this is kind of a funny question. Is your husband still in school? 

Kate - 00:46:49: No, thank goodness. With 38, I told him it was time he got a big boy job. 

Jon - 00:46:54: Yeah, he was like. Kate - 00:46:55: He finally finished his training. Yeah, he's a surgeon at Children's Hospital. 

Jon - 00:47:00: He's like, okay, thank God. Like, you can't be doing this forever. You can't be doing this forever. Kate - 00:47:05: And I told him one of us has to have a stable job. Biotech is too crazy. 

Jon - 00:47:09: Yeah, it's too crazy. I need this kind of base layer. I need you to just read this wrong. Absolutely. And if you can give any advice to your 21-year-old self, what would it be? 

Kate - 00:47:18: I think it would be just believe in yourself and stick to your guns and network and don't be afraid to take risks. 

Jon - 00:47:28: Absolutely. And I think for anyone who's out there and, you know, as you're kind of like we were talking about that existential dread of like, you know, what's next? I think that's a tip that, you know, anyone can find value from. And I think something that I've learned from you is about just seizing the opportunity to get experience and learn is so critically important because like you really did have this soup to nuts kind of like experience. Kate - 00:47:53: Yes. 

Jon - 00:47:55: Small, like small company, big company, basic research, drug discovery, clinical work. And it's like you can read it in a book, but there's nothing that replaces just like getting your hands dirty. Like you built a vibarium. Kate - 00:48:06: Exactly. 

Jon - 00:48:07: And both like figuratively and literally hands dirty. And so, like, I think that aspect is like I learned a lot and perhaps I should have been more courageous on my side. Maybe leaving Berkeley would have been good. That would be the first step in courage. But. But, Kate, thank you so much. I've, you know, again, I could do this for hours and hours and hours, but you've been so generous and hopefully I get to see you soon. I know you're not going to JPM this year, but maybe on the next go around now we can get a cup of coffee. 

Kate - 00:48:36: Yeah, no, thank you so much. I really enjoyed the conversation and really look forward to getting a chance to meet you in person. Thank you so much. 

Jon - 00:48:43: Thanks, Jon. 

Outro - 00:48:46: That's all for this episode of The Biotech Startups Podcast. We hope you enjoyed part two of our conversation with Kate Yen. If you did, consider subscribing, leaving us a review and sharing it with your friends. Be sure to join us for our next series featuring Becky Beattie, CEO at LaunchBio. LaunchBio is a non-profit dedicated to supporting high-growth life science companies. Through its national network of life science hubs, it builds an inclusive and collaborative ecosystem that drives industry growth. By connecting entrepreneurs with knowledge, capital, and talent. LaunchBio fosters innovation to advance human health. As CEO of LaunchBio, Becky leverages over 20 years of life sciences experience, blending molecular biology and business experience to drive impact. Since 2017, she has expanded LaunchBio's national presence and established the highly successful Investor Connect series, the NextGen VC forum and podcast, and biotech career workshop XTM education program for high school students. Becky has also fostered collaborative relationships with ecosystem partners that include accelerators, universities, investors, and industry leaders. With a wealth of industry experience, a history of driving biotech innovation, and a passion for building highly inclusive, high-impact ecosystems, Becky offers valuable insights you won't want to miss. The Biotech Startups Podcast is produced by Excedr. Don't want to miss an episode? Search for The Biotech Startups Podcast wherever you get your podcasts and click subscribe. Excedr provides research labs with equipment leases on founder-friendly terms to support paths to exceptional outcomes. To learn more, visit our website, www.excedr.com. On behalf of the team here at Excedr, thanks for listening. The Biotech Startups Podcast provides general insights into the life science sector through the experiences of its guests. The use of information on this podcast or materials linked from the podcast is at the user's own risk. The views expressed by the participants are their own and are not the views of Excedr or sponsors. No reference to any product, service or company in the podcast is an endorsement by Excedr or its guests.