The Founder Identity Trap: Navigating the Hidden Mental Cost of Leadership | Nicole Paulk (Part 4/4)

Intro - 00:00:06: Welcome to the Biotech Startups Podcast by Excedr. Join us as we speak with first-time founders, serial entrepreneurs, and experienced investors about the challenges and triumphs of running a biotech startup from pre-seed to IPO with your host, Jon Chee. In our last episode, Nicole shared arriving at UCSF, asking whether a single AAV vial could treat multiple diseases, founding Siren during COVID lockdowns as a sneaky way to get back to the bench, and landing a $6,000,000 seed from Founders Fund with no board attached. If you missed it, check out Part 3. In Part 4, Nicole Paulk unpacks why being a first-time female technical academic founder CEO—a combination she says everyone called the worst possible thing you could be—is actually the best CEO training imaginable because academia teaches you to do more with nothing. She also breaks down how that $6,000,000 seed lasted three and a half years, why going all in on unglamorous CMC optimization from day one is the most important thing Siren ever did, and why she loves nothing more than being the underdog Cinderella story no one expected to make the Sweet 16. She closes with advice to her 21-year-old self: follow the weird little sprites the universe throws at you, the ones that feel off-script. And with gratitude that just two weeks before this recording, Siren cleared its FDA IND and became a clinical-stage company.

Nicole Paulk - 00:01:53: So you need a younger team who believes and who is really excited by the science and wants to do the science. And going back to what we said before, I think not having a board was huge because we weren't constantly wasting time preparing decks, but we also weren't getting brought off and distracted by tangents where they're like, "Oh, well, I—I thought up this question, and I'd like you to prepare a response for it before the next board meeting on, like, whatever, some—something." You're just like, "Alright. Now we've gotta, like—"

Jon Chee - 00:02:26: Yeah. Yeah.

Nicole Paulk - 00:02:27: —this whole deck just to, like, scratch some thought itch that they had. And, again, not that that is not important when you become a certain stage, but, like, when you're really early, it's just, like, not. And this is still probably true, uh, and probably just an exception to the rule: the perception that academics make bad CEOs. Like, can you imagine a worse CEO than a first-time female, young, technical, scientific founder CEO straight out of academia who's never led a company before, who's, like, gonna be the CEO, not the CSO, like, just dripping with bad? Like, it's just, like, the worst possible thing you could be. And I—I push back on that with every fiber in my being that, no. Um, you're wrong. It was the best possible CEO training I could ever have because being a scientist in academia, where there's no money because you're just constantly scrapping for grant money that doesn't exist, is you find a way to do science with nothing. So, like, not having a piece of instrumentation is, like, not a block. You're like, "Oh, I'll just find someone who'll let me use theirs." And finding ways to do things collaboratively. We're like, "Hey. Could you—wanna go halves on this experiment? And we'll, like, all analyze the tissue in this way and you analyze it in this way," or, "We'll, like, go halves. Like, you use the mice first to do some observational behavioral study, and then we'll use them after you to do this, like, therapeutics thing," or whatever. And then, like, finding ways to just, like, do more with less and be really scrappy. And so that just, like, being cheap paid off so well leaving academia and just being like, "Oh, we ain't buying name brand." Yeah.

Jon Chee - 00:04:12: Yeah. For real.

Nicole Paulk - 00:04:14: We're gonna go get some used equipment, and we're gonna go get the off-brand whatever, plasticware and blah blah blah blah. And we're just gonna be really cheap about it and just being really scrappy and just not waste—like, we didn't have merch for years and, you know, just like all the nonsense that these big companies, you know, 200 people. And it's like, you get hired, and you've got, like, a welcome package sitting on your desk with, like, branded pens, cups, and hats, and notepads, and backpacks, and hat. And it's just like, what is all this stuff?

Jon Chee - 00:04:50: Yeah. Yeah.

Nicole Paulk - 00:04:51: Like, I bet those people would rather either have that as benefits or as pay. Yeah.

Jon Chee - 00:04:56: Yeah. Yeah. Or—

Nicole Paulk - 00:04:57: —more money to do their science, but, like, no one needs a branded hat on day one. They just don't. So, yeah, it's just a different attitude. So I think, like, coming from academia prepared me to just do more with less and just—I think my personal personality of just being, like, a mile a minute, like, five-year-old stuck in, like, a 40-year-old's body paid off because I'm just, like, "Let's do more."

Jon Chee - 00:05:17: Yeah. Yeah. Yeah. Yeah.

Nicole Paulk - 00:05:18: Yeah. I know. Let's just do more. I was just—it's like a dog seeing a squirrel. I think there's also something about, like, loving it in a way that I don't think it's impossible if you're a brought-in CEO to have, but it's a lot harder to just really passionately, personally believe the way that, like—I mean, like, Siren is, like, literally—like, it is a child. Like, it is mine. It is my baby. I would give a kidney for Siren if she needed it to stay alive the way that someone who's just brought on to, like, play the role through this period. Like, "Oh, I'm the CEO who will take you from seed to A, and then another CEO will come on, and they will take you to clinical, and then another CEO will come on and be their commercial CEO." And just, like, knowing that you play this role—not that there's not a place for that, and that's, like, all well and good. Not every professor is gonna leave their lab to go start their company, and many of them need a CEO to come in. So there's a place for that, but I think it is just different when it's your, like, life's work. And it is your reason for waking up and it consumes you. That's pretty irreplaceable, and you kinda can't fake it. So I think that helps us in crazy ways to just do more with less. And, I mean, some of it is just straight-up luck. Like, we've just lucked out with amazing people who just, like—I'd love to say I have some, like, brilliant hiring scheme and, like—this is just luck. We just have really lucked out with, like, amazing people. Like, I have no, like, amazing epic—like, "These are the five questions you must ask all new hires, and this is, like, the epic way of retaining that." It's just, like—I think we just, like, unbelievably lucked out with amazing people, and, uh, like, one amazing person begets another amazing person. Like, it's just, like—it's so obvious to me. I'm just like, we have, like—we've spend no time thinking about, like, "What is our culture and how do we perfect it and what do we do?" It's just like, man, just, like, be good to people. Yeah. Like, it's just—that's it. Yeah. Yeah. Be reasonable and good and, like, work on cool science. And then, like, you won't need to push them to work hard because they'll just do it on their own. We got a scientist this weekend who's coming in this weekend just on his own. He's just gonna do it. Like, I—we're not like, "You need to come in this weekend. 996." Like, he's just gonna do it because he's great, and he really likes it and is pumped and just wants to know the answer. So, yeah, some of it, I think, is luck. Some I think is also just, like, the power of a small team. Right? Every one of our meetings is an all-hands, so there's no, like, communication loss. So I think even if, like, miraculously, like, I found a paper bag with a $100,000,000 on it on the sidewalk that fell out of some drug bust car that I would absolutely take and go deposit in our SVB account. But, like, even if we, like, magically fell upon, like, a bunch of money tomorrow, I would not, like, "Oh my gosh. Let's go hire 15 people." Mm-mm. No. Like, small is good. Like, I like being a small company, and I also like—and maybe some of this is, like, the sports part of me. Like, oh, I love being the underdog.

Jon Chee - 00:08:13: Yep.

Nicole Paulk - 00:08:15: Like, near fantasy level. Like, I love being the underdog. I love a Cinderella story. I love a Hail Mary pass. Like, I live for that, like, March Madness, the inner-city group that nobody thought would ever make it to the Sweet 16, and they just, like, keep winning. And, like, all of a sudden, like, they have fans who were never their fan who never even heard that they existed before, but then you're like, "You know what? I am rooting for," what you know, whoever. It's like the World Cup and, like, your team fell out, and all of a sudden, like, Morocco's in it. And you're like, "Go, Morocco!" Like, yeah.

Jon Chee - 00:08:53: Yeah. Yeah. Like, yeah. Yeah.

Nicole Paulk - 00:08:55: Brazil beat Germany, beat Italy. Like, yeah.

Jon Chee - 00:08:59: Yeah. Yeah. Yeah.

Nicole Paulk - 00:09:00: I think I just love the Cinderella story, underdog, small team that everyone doesn't expect big things from coming out of left field and just being like, "Watch me. I can't wait for you to see what we can do." So, yeah, maybe some of it's just that too. Just the competitive, small underdog wanting to—to win the state championship that just never goes away.

Jon Chee - 00:09:28: And I was gonna say too, something about—you know, you talk about, like, these, like, super big rounds and kind of, like, smaller rounds. I think also having these, like, smaller rounds go the distance makes for a more sustainable capital market, too.

Nicole Paulk - 00:09:47: For sure. It is a win for everyone. I mean, I would love to have more money right now. I mean, everyone feels a little like—

Jon Chee - 00:09:52: I win.

Nicole Paulk - 00:09:53: —and they're, like, looking at, like, "How many months of ramen do I have?" But it is probably for the best to be a little bit scared.

Jon Chee - 00:10:00: Yeah. Right? It's, like, long-term the right thing because, like, if every company needs to be funded with a hundred million, the return bar is just so high.

Nicole Paulk - 00:10:10: Yeah. It just becomes impossible.

Jon Chee - 00:10:11: It becomes impossible. Just mathematically impossible. And so it's just like—I always thought about it just like, what if we could just do way more with less and make, like, a more sustainable, like, capital market for science rather than, like, "Oh, you better raise, like, hundreds of millions of dollars or else you're cooked"?

Nicole Paulk - 00:10:29: Yeah. The thing too is that, like, if you go into it with that framework, like, "I'm only gonna raise what I need, but I'm gonna be very capital efficient with it," rather than, like, waiting until you need to start being really scrimpy. If you do it from day one, like—I mean, Christ, our $6,000,000 seed lasted us, like, three and a half years, and we still had money. At the end of that, it gives you time to do more thoughtful science, and there's good and bad things with time pressure. I very much like being out in industry because it moves so much faster than academia. So it—it fits my personality style, but bad things can happen when you rush. And there are moments where you need to put jet fuel on something. It's like, "Let's go." But there are times where you need to be thoughtful, and I think some of those times are the very earliest moments as a company so that you don't make, like, penny-wise, pound-foolish decisions and, like, skimp on things like CMC that will absolutely come to bite you later down the road. And when they—when they bite you, they will be unsolvable or very expensive, both in terms of time and money. And had you just spent, like—well, you don't have to go as crazy as we didn't spend years. But, like, even just, like, spending six months on CMC and, like, thoughtfully optimizing things in the first six months as a company before you, like, plant the flag and say, like, "This is how it's gonna be; we're not gonna change it anymore," can change the literally, like, the entire trajectory of your company for all of time in a way that you can never get back. And so being really thoughtful with capital and telling yourself, like, "I am going to force myself to use this money over three years," even though I could raise. Like, maybe we're gonna hit an interesting milestone at year one, and maybe we could raise again. But telling yourself that you're gonna use that money for three years forces you to kind of, like, think through how you're gonna do things differently and, like, "How am I gonna survive that long?" And you don't do fufu stupid experiments that you don't need to do, but you do do the ones that you do need to do and you do them well because you don't have enough money to repeat it. And so it just—it just puts you in a different headspace that I think is where you kinda need to be. It's like a weird dichotomy because it's both how can you do more with less and faster—because, like, oh my god, AI in China. Yeah. It's like, how can you both move faster and more slowly?

Jon Chee - 00:12:50: Yeah. Yeah. Yeah. Yeah.

Nicole Paulk - 00:12:51: Yeah. Use—put the spacetime continuum and, like, find their dimension and both be fast and slow at the same time and know when to turn one on and the other one off, and—and that—that is a learned skill.

Jon Chee - 00:13:04: For sure. And I think I had a similar experience in that. Uh, I mean, it's like, look, if you're—if you're able to be frugal and, like, make things work on, like, a shoestring budget, you think those habits, like, are deeply ingrained. And then as you, like, layer in capital when you actually need to start flooring it, you get, like, these, like, kind of, like, logarithmic kind of, like, acceleration curves. And, like, for me—again, this is, like, me coming out of the lab and not knowing better and not knowing risk management or anything.

Nicole Paulk - 00:13:34: No one teaches that.

Jon Chee - 00:13:35: No one teaches shit about that.

Nicole Paulk - 00:13:36: No one teaches that at all.

Jon Chee - 00:13:38: No. And you're talking about, you know, back in the day, I think it's getting better, but where academia was, like, a very much a separation of church and state. And if you bring up anything but being a professor or, like, the professor's research, you're just gonna be, like, ostracized until—like, I brought up business and, like, the concept of Excedr, like, back then. And I would just got, like, laughed out of rooms and just, like—it was not fun. It really sucked. I was like, "I thought we were friends. Like, I'm just trying to help." So—and then Excedr is not a venture-backable company because, like, we buy a—a shit ton of equipment, and, like, VCs don't really like that. I guess—I guess capital intensity is now cool, like data centers and—and stuff like that. But—

Nicole Paulk - 00:14:17: Gotta rebrand, man.

Jon Chee - 00:14:18: Yeah. Yeah. Exactly.

Nicole Paulk - 00:14:19: You're Deep Tech now.

Jon Chee - 00:14:21: Yeah. Yeah. I'm Deep Tech. Exactly. Yeah. Exactly. Exactly. Just get a monster check. So the first piece of equipment I bought was with my life savings, and there's a certain amount of, like, what you said, like, focus and, like, when everything's on the line. And then you have to be super frugal. Like, not to say that everyone should put their life savings on the line.

Nicole Paulk - 00:14:42: Yeah. No.

Jon Chee - 00:14:43: No. No. No.

Nicole Paulk - 00:14:44: But many startups are terrible ideas and should go under.

Jon Chee - 00:14:47: Yeah. Yeah.

Nicole Paulk - 00:14:47: But—

Jon Chee - 00:14:48: —there's, like, that forcing function, like, of—of attention and care. It just, like, builds that discipline in your company, and then that's the DNA of the company versus, like—it's like, you know, we've all gone to school with kids or have seen kids who are just, like, granted a ton of money without having to earn it.

Nicole Paulk - 00:15:08: Yeah. They got bought a Grand Cherokee new car for their sixteenth birthday, and you're like, "Woah. Mine was $500, and it's held together with, like, a prayer and some duct tape."

Jon Chee - 00:15:17: Exactly. Exactly.

Nicole Paulk - 00:15:18: Exactly. Screwdriver because there's a key broke off in the ignition.

Jon Chee - 00:15:21: Exactly. Exactly. And, like, I always, like, think about that parallel because, like, I'm still driving my beater, like, '06 Honda, and then that's, like, what I've been driving for ages. But it's kind of like the—it's a similar thing, like, in kind of like entrepreneurship when you're, like, you just get granted this, like, mountain of cash.

Nicole Paulk - 00:15:36: Yep.

Jon Chee - 00:15:37: And you have not yet built your kind of, like, frugal, disciplined, cost-efficiency kind of mindset. And it's, like, really hard to do when you're just seeing, like, a mountain of cash. Like, any human being would be, like, "I guess I gotta spend this." Like—

Nicole Paulk - 00:15:52: Well, we also just do a really bad job of—and it's both in academia and industry, but, like, we just do a really bad job of preparing people to kind of, like, handle these—these weights. And one of my biggest beefs, like, uh, like, god, if I could change anything in, like, the culture right now—you know, it's a challenging biotech market, both, like, the XBI, but also just, like, even for private companies like fundraising. It's just a challenging scientific moment right now. There's not as much M&A happening as people would hope. There's not as many IPOs as people would hope. We've got interesting regulatory pressures and pressures from—and just like there's a lot of things happening right now at once. Like, the Venn diagram of, like, crazy things happening is—is intense. So it's a challenging moment, and I keep seeing this thing happening that I can't stand where founders either do this to themselves, they invite themselves together to meet, or someone will coordinate a cocktail event, a food event, or whatever. You know, like, a bank will do it or a VC will do it or a vendor will do it, where they're like, "Oh, hey. We wanna get, like, a bunch of you together, a bunch of you founders and CEOs together to talk and share ideas, and we're gonna have, you know, whatever, some drinks or some passed appetizers or whatever." And that sounds fine on its surface. You're like, "Oh, yeah. We should all talk right now about the moment and—" And what ends up happening are these multi-hour bitch-fests where everybody gets together and they just—it's like competitive complaining. Who has it worst?

Jon Chee - 00:17:18: Ugh.

Nicole Paulk - 00:17:20: Who has the least amount of money? And who's about to go under? And who is about to need to do layoffs, and who has the worst board, and who has the most challenging competitor that just screwed them over, and who just had some nightmare scenario with an employee that sued them, who just had a huge contract fall through, who—you know, where—blah blah blah. I'm just, like, ranting and making things up. It's just like this complain party, and it does nothing. And it is performative, and it's become competitive. And it's just—it drives me absolutely up the wall. And I, like, have stopped going to these even though, like, some of these are, like, friends that are, like—I miss, and I wanna see them. But I'm like, "I want to see you, but I do not wanna hear about why your company is failing." I don't think it's healthy for you. I don't think it's healthy for me. I don't think it's healthy for the industry. I don't think we should be doing this. It doesn't mean I don't think we should all be getting together. We should, but we need to, like, completely flip the script and not bitch and piss and moan and complain, but, like, you know, the classic line, "Don't bring me problems; bring me solutions." Like, let's get all the founders and CEOs together for three hours. And, like, whatever. There's 10 of you, and everybody gets twenty minutes. I do not wanna hear the backstory. I don't care. Bring me one problem that you have that you need help with. You have a problem with your board. You have a problem with an employee. You have a problem with an experiment. You have a problem with an investor. You have a talk coming up, and you don't know how to frame it. Whatever—whatever the thing is where you're like, "I need help with this thing, this action item, this deliverable, this situation." And there's no nuance. There's no discussion. There's no bitching. It's just: here's my situation. Here's the problem. Here is the ask. And for twenty minutes, like, set a timer. We all, the rest of us, and we're like, "Let's solve that." Like, whatever. You need an intro. You need a solution to how to deal with your board. You need a—whatever. And then, like, for twenty minutes—again, we don't all complain, "Oh my god. I had that too. Oh my—" No. Just like, get out your laptops, and let's solve your problem. How can we solve it? Maybe it's I can intro you to someone that I know that just dealt with that, or let's, like, craft the email response to your vendor, or, "Oh, we have that dataset that you need. Why don't we just, like, you and I collaborate? And, like, I'll give you this if you can give me that, and let's just, like, handshake on it like the old days," or just, like, whatever. Let—let's solve your problem together collectively in twenty minutes, but no complaining, no bitching, no comparisons. Just like: bring your one problem and you get twenty minutes, and then we switch. And that way, everyone knows it's a good use of time because they're gonna get their thing answered. So no matter what, it's not like, "Well, god, I went to this whole event and I helped everyone else, but I didn't get help." It's like everyone—you cannot leave early. Like, you're coming for the whole event. You can't just get your thing answered and then bail. Like, everyone stays for the whole whatever set period of time—one hour, two hour, three hours, whatever it is. You get your big, gnarly, scary thing, and it's like Chatham House Rules. You can't talk about it to anybody else afterwards. And it's like, "Let's help each other get out of the situation we're all in rather than all just competitively, like, complain about who has it worst." Like, it's just not helpful, and I don't think it's putting us in a good headspace. And we all know so much about how we could all help each other. And I think we are both our, like, biggest nightmare and, like, our biggest opportunity. Like, we can help each other get out of this, and I think we just need to stop complaining together.

Jon Chee - 00:20:58: Love that.

Nicole Paulk - 00:20:59: Like, that is my wish. Like, no more founder meetups where we all just complain for three hours. Let's work together on solutions together.

Jon Chee - 00:21:12: Yep.

Nicole Paulk - 00:21:13: I've, like, started not—like, if I get invited to something and it—it doesn't seem like it's gonna be competitive complaining, and I get there and it's, like, ten minutes in, it's like, "Oh, we're all just gonna start competitive complaining." Like, just, like, go hug the host. I'm just like, "Bye. I gotta go."

Jon Chee - 00:21:27: Gotta leave.

Nicole Paulk - 00:21:27: "But we're—we're about to start the seated plated dinner," and I'm like, "I don't care. I—I gotta go." Yeah. I—I can't do this anymore. It's too much. It's not a waste of time. It's just, like, not healthy to do.

Jon Chee - 00:21:40: Yeah. Yeah. No. I agree. I'm gonna play devil's advocate to myself on my commentary about, like, the power of, like, focus on the company and the company being Excedr everything. I think, like, recently, you could take everything too far. Right? And this was something I think I probably took too far, where the company is, like, synonymous with your, like, identity. And, like, whatever setback the company has becomes, like, a setback for me. I was, like, talking to my therapist about that, and I was just like, "Oh, like, that's why I feel like shit." Like—

Nicole Paulk - 00:22:15: Yep.

Jon Chee - 00:22:16: And through, like, you know, exactly what you described, like, the 2020, '21, and everything after that, when you're so inextricably tied to this thing, it can be incredibly powerful that you'll do things that'll go above and beyond what normal people would do for the thing.

Nicole Paulk - 00:22:33: Is it both a blessing and a curse? And it's a very tightrope that you're walking where it consumes you, and that can be both a good and bad thing.

Jon Chee - 00:22:42: Yeah.

Nicole Paulk - 00:22:43: Finding a way to—to very delicately walk that tightrope.

Jon Chee - 00:22:47: Yeah. It's hard. It's, like, super hard.

Nicole Paulk - 00:22:50: Not wrapping your entire self-worth up in whether or not your company works.

Jon Chee - 00:22:56: Yeah. But then you wanna be able to harness that power to just, like, fight through insert, you know, problem. Right? And, you know, I'm still learning about it, but, like, I—I think I've—I've seen more—like, years ago, it was, like, a lot of, like, the hyperfocus and seeing the benefits of that. And then as, like, things always happen in business, like, no shit happens, and you're like, "Oh, woah. There's, like, a dark side to this."

Nicole Paulk - 00:23:23: Like, you could only push so far, too hard for so long. Like, there will always be deadlines where you have to just absolutely leave nothing on the field and just get it all. It takes every ounce of everything that you had to hit that deadline, but then, like, you can't do that permanently. That is it. Like, the eternal challenge, I think, for founder CEOs is knowing how and when to dial it up, but knowing that you have to dial it back, even if it's for a day, a week, a month, before you ramp up again. Otherwise, it will consume you.

Jon Chee - 00:23:55: For sure. And it'll consume those around you, too. Like, I think something about, you know, founder, CEO, the experience doesn't really get talked about is the effect it'll have on, like, your friends and family and, like, loved ones, too. It doesn't happen in isolation. Like—

Nicole Paulk - 00:24:14: You will affect everyone. Right? Strangers, your pets, your employees, your friends, your family, everyone. You are an electrical being, you know, existing in the universe and, like, your aura, your vibe, your everything will—will affect absolutely everything around you. So we are all learning this in real time. Like, how far can you push it?

Jon Chee - 00:24:33: Without redlining.

Nicole Paulk - 00:24:34: Without completely redlining. You know, if, you know, like, you're into race cars or something, like, are you running rich or are you running lean? Both are bad, but, you know, how far can you push it in either way before you have a catastrophic engine failure?

Jon Chee - 00:24:48: Yeah. Yeah. Yeah. Exactly.

Nicole Paulk - 00:24:49: You can push it, but, like, you're gonna need to ease off and go refuel.

Jon Chee - 00:24:54: I'm, like, learning, like, about, like, the need to, like, set those boundaries from time to time. Like, some—exactly what you said. Sometimes there's a deadline. Sometimes there's a deal that you need to, like, just absolutely get done, but, like, that can't happen, like, forever all the time, which was, like, a—a mode of being, I think, I—I had for, like, a really long time. But I, like, started to feel, like, the negative ramifications of that pretty recently, honestly. And I think it was, like, as—I think I saw folks who were—you know, I don't have kids, but friends are starting families. And there's a kind of seeing what that all meant and, like, not being able to be present. You know, there are things above or—or outside of business that are also important. I was like, "Oh, shit. Like, I'm not present. I'm not here. I'm just, like, thinking about insert business thing," and that really sucks. But no. Like, I think your idea for a better meetup, uh, like, I'm a big fan of that.

Nicole Paulk - 00:25:52: Yeah. Like, we desperately need to spend time with each other, you know, as a field and as a community because one of the other big challenges, right, of being a founder CEO is, like, it's lonely at the top. Right? Like, you can't be friends with your employees, and you will always have that power dynamic, particularly as CEO, that you are the one person who can fire anyone at—at the whole company, and that power dynamic, no matter how friendly y'all seem, is ever-present no matter what. And, you know, you can't get away from that. And so it is lonely at the top, and you pair that with, like, overworking, and then now all of a sudden it's like, "Man, I haven't seen another human being in, like, a friendly scenario." And you're like, days, weeks, months, quarters, maybe even years. You know, we are a social species. We need other people around us where we do things, and we're still gonna be founders. So still gonna always talk about our companies.

Jon Chee - 00:26:51: Yep. Yep. Yep.

Nicole Paulk - 00:26:52: Like, you won't often change that, but I think we can do it in a more healthy way. And I think that healthy way is, yeah, just not competitively complaining and, like, build each other up and let's help each other. And I think that is a way to achieve both things: the meeting up and seeing other human beings that miss and love and wanna talk to and wanna hear about. Also, the—the other thing which can also happen, which is, like, competitively trying to show off.

Jon Chee - 00:27:17: Yeah. Uh, no.

Nicole Paulk - 00:27:19: "How's everything?" "Everything's great. It's great."

Jon Chee - 00:27:22: Yeah.

Nicole Paulk - 00:27:23: "Great. Everything's great." It's like, okay. You good?

Jon Chee - 00:27:27: Yeah. That's cool.

Nicole Paulk - 00:27:29: Let me just talk, and then we don't have to, like, compete about who has more money or awards or data or FDA designations or—or—or patients or whatever. We can just, like, talk. So I think both are—are really dangerous. It's, like, competitive besting of each other and also, like, competitive complaining. It's like, "Let's just meet up and, like, help each other." Like, that to me sounds, like, the most fun.

Jon Chee - 00:27:52: Yeah. For sure. I think too, just like being in the Bay Area, it's a very high density of founders.

Nicole Paulk - 00:27:58: For sure.

Jon Chee - 00:27:59: Yeah. So, like, you kind of get this, like, crazy resonance. And also with everything going on in AI is, like, there's a lot of, like, animal spirits going on. But hearing about your stories and—like, there's so many times where I was just, like, thinking about, like, my own journey, and I was like, "Oh, it's like—I felt the exact same way. I had that late kind of, like, bloomer. I didn't know what the hell I wanted to do. It's like—" and—

Nicole Paulk - 00:28:24: And that's okay.

Jon Chee - 00:28:25: Yeah. That's totally cool.

Nicole Paulk - 00:28:26: An unscripted life is okay.

Jon Chee - 00:28:28: Yeah. And I think, you know, exactly what you said. I carry that with me to this day, and I think there's, like, so much benefit in just, like, this kind of, like, exploratory kind of, like, "Let's just see where this takes us." And then from there, optimizing. Like, then at that point—and it oscillates. Right? Like, you can go for, like, a period of optimization, and you can go back to exploration and just, like, being—exactly what you said, like, toggling it or walking the line of, like, hyperfocus. Like, "I'm gonna put my life on the line for this thing. Like, I need to have some boundaries and see my friends and talk about other things." Like, and on a net basis is, like, you ultimately come out balanced, like, through that all. But, um, Nicole, you've been so generous with your time. This has been super, super fun and love learning about everything you got going on. And in traditional closing fashion, I have two questions for you. First question: if you can give any advice to your 21-year-old self, what would it be?

Nicole Paulk - 00:29:23: I wish I would have told myself a little bit earlier to, like, just kind of, like, follow those little—like, sometimes it just feels like the world kind of opened up for a moment and, like, peeked at you and, like, was like, "You could do this. You could go that way. You could follow that little—that little spark, that little sprinkle you saw in the sky, like, that little thing," whatever that was, and just kind of being a little bit more open. I mean, in general, I think I do a very good job at this. But I think even back then, I could have done a little bit more of kind of keeping things unscripted and, like, not being afraid to kind of walk off the path, and you can come back, but whatever. But just, like, when you have, like, those little moments where you were like—you'd come home and, like, talk to your roommates, and they'd be like, "Oh, what happened today?" And you're like, "It was so weird. This happened." And then you all just kind of, like, passed it off, and it was—and you didn't, like, double down on it and be like, "I wonder what would happen if I just went back and talked to that person. I wonder what would happen if I went back and picked up that thing I found on the ground. I wonder what would happen if I had followed through on that offer to ask me to participate in that thing," where it felt like it wasn't on your path and so you just kind of ignored it. Because I have been so surprised now in my forty-two years, I have been so surprised how many times really good things have happened when I've done that. And I wonder if I had more purposefully and forcefully followed those little moments rather than kind of occasionally just letting them happen. I wonder what would have happened if I would have more purposefully tried to really, like, get out of my comfort zone and follow some of those weird little sprites in the universe. Like, what would be different? Maybe it would be worse. I don't know. But, like, I'm just curious what would happen if I would go back and follow some of those weird—answer the weird Craigslist ad.

Jon Chee - 00:31:04: Yeah. That's literally what I was—

Nicole Paulk - 00:31:05: Thinking. The weird, you know, note that you found on the sidewalk, offer to do the weird event that is not in your space or your field or thing that they just needed an extra person. You know? If I had done more of just the weird oddball things, like, what would that have become? What would that have taken me? I'm just curious what, like, that alternate writing of my textbook could have been. I mean, I love my life. I wouldn't change anything, but I'm just, like, curious. In another dimension, could I see, like, what another life could have been? So, yeah, maybe I'd—I'd follow more weird universe suggestions.

Jon Chee - 00:31:37: It's like creating serendipity more forcefully.

Nicole Paulk - 00:31:40: Purposing. "Like, that was weird. I don't understand it. I'm gonna go investigate that."

Jon Chee - 00:31:45: Yeah. I'm a go look into this, and then I felt the same way. Like—and for me, I think I talk about this example a lot, but it is, like, I'm going to, like, big, like, meetups and stuff like that. Not my thing. Like, they're like—but I—I forced myself to do it. And I'm always—I come out, I'm like, "Why was I so, like, anti this?" I was like, "This is awesome. I met some great people, had some, like—" and it just kind of, like, always, like, surprised. Like, when you pull yourself out of your comfort zone, you'll surprise yourself, and you will be surprised.

Nicole Paulk - 00:32:14: It's like not wanting to go out because you're like, "I'm tired," and then you go out. You have an amazing time.

Jon Chee - 00:32:19: Yeah. "You should—maybe I should do this."

Nicole Paulk - 00:32:22: Put your big girl britches on and go out. You have a great time.

Jon Chee - 00:32:25: Yeah. Maybe I should do this. And then the last closing question is: would you like to give any shout-outs to anyone who's supported you along the way?

Nicole Paulk - 00:32:33: So many. My goodness. I mean, just like every professor I ever had, not even just professors, like, further back. Like, every teacher I ever had. I'm a handful. As folks have probably noticed, I, like, can't even sit in my chair. I'm just so squirmy. I'm just—I have to move. I'm very gesture-y with my hands. So it's just like every person who has ever had to put up with me ever, particularly if it was like a teacher or a professor—like, thank you for dealing with me and not quashing my spirit and allowing me to continue to be this just obnoxious, loud, energetic, curious person who just keeps asking, like, "Why? Why?"

Jon Chee - 00:33:12: Yeah.

Nicole Paulk - 00:33:12: You hear it. And there's like, "I don't know why the sky is the way that it is. It's just—it's blue." So, like, all of humanity for just putting up with me and, like, every specific teacher and professor I ever had, like, not quashing my spirit and just letting me be this, like, wild and crazy, like, little gremlin who's just running on Earth. And a pre-thank-you, maybe, is in order. Like, we just became a clinical-stage company, like, two weeks ago or something. We just got our IND-approved papers—trial for our very first drug, for our very first everything. And just thinking about it makes my hands sweat.

Jon Chee - 00:33:49: Yeah.

Nicole Paulk - 00:33:49: Like, actually, you can't see it, but, like, they're swelling. They're red and they're sweating. Yeah. Because I'm just thinking about this, like, profound moment that is, like, single-digit months away. Right? We're very close to, like, actually dosing the first person. We're just working on getting the sites activated, and it's just like, man, like, this is an idea I dreamt up with, like, some technicians on a whiteboard back in 2017. And, like, fast-forward now, we've got all this data, like mice, pigs, and all this stuff. And how many people have given so much money and so much time and who come to be employed by me and are trusting me to, like, help me pay their rent. All of this that has led to this moment where, like, now there's gonna be a patient. And, like, our first patient will probably get dosed at UCSF because it's our lead site. Like, someone who's probably walking around San Francisco right now doesn't know that they have brain cancer. They don't know it yet. Because most brain cancer patients, right, they present with, like, a seizure or a stroke or the worst headache of their life, and they go to the ER. And they find out, like, "Oh my god. Your brain is—" It's not something that runs in families. Right? They're all kind of spontaneous. This person has no idea they have brain cancer. And they're gonna show up at the ER at UCSF, it's like a seizure or stroke or headache. And they're gonna be like, "We don't know what's wrong. We gotta do an image," you know, CT or MRI or something. And they're like, "Oh my gosh. You have a mass. Like, we need to do a biopsy," and, like, it's just gonna throw their whole life just, like, absolute cattywampus. Like, there was the day before and the day after that day, and their life will never be the same after that day. And they're gonna find out, like, "Oh my gosh. You have a brain cancer," and they're, like, there's no effective drugs or treatments. There's nothing. Like, all we've got are experimental therapies, and this person is gonna take, like, the most magical thing that they have—their life. You only get one. The most precious thing any of us owns on this life is the fact that you are alive. They're gonna take their life, and they're gonna hold it in their hand, and they're gonna be like—you know, like—"Well, there's this clinical trial you can start." And it's a true first-in-human trial. There has never been a human being that has been dosed with an AAV gene therapy for any cancer, much less a brain cancer. Do you wanna be literal, actual patient number one? And this person is gonna take their, like, one wild and precious life and be like—I—and, like, there's a firewall. Right? They can't know who I am, and I—they can't—I can't know who they are. Right? There's all kinds of HIPAA compliance, but, like, we will both be, like, staring up at the moon. And, like, they are gonna be, like, "I'm gonna go on this wild journey with you, and I'm gonna be patient number one and try this, like, experimental—" like, the definition of experimental, this experimental therapy. And, like, they'll say yes to their clinician. And I will get a phone call that they've consented, and they've said yes, but I won't get to know, like, you know, it's—it's Peggy Anderson. Like, I won't get to know, you know, their name, uh, until later. And, like, we're both gonna be, like, staring up at the moon and being like, "Oh my gosh. Mhmm. Can't believe this is happening tomorrow." So I am gonna pre-thank-you and shout out to whoever that person is. Like, we're on this journey together. I hope it works for you. I'm gonna be, like, crying and sweating.

Jon Chee - 00:37:02: Yep. Yep.

Nicole Paulk - 00:37:03: It's just, like, unable to sit and think about that moment and just everything that has led up to that moment for, like, all of the literal, like, hundreds, possibly even thousands of people at this point that has led up to this moment. So pre-thank-you to that person, whoever you are.

Jon Chee - 00:37:16: Wow. Well, I—I love that. And, also, I don't know any better place to end things. Yeah. That's—that's absolutely—it's beautiful. This actually—

Nicole Paulk - 00:37:25: —of my life.

Jon Chee - 00:37:26: Yeah. It's actually beautiful. So, Nicole, thank you so much. This has been super freaking fun. I'm super pumped for you. I'm super excited for you. And the way I just saw that, like—I was just so beautifully, like, in my mind of, like, that moment when someone makes that decision. My hands are sweating now.

Nicole Paulk - 00:37:43: Right? My hands are—but they're sweating. I think about it every day. They're still sweating.

Jon Chee - 00:37:47: Yeah. My hands are sweating. So thank you so much. The next time you find a moment to take a breather, I'd love to grab coffee, a snack, and just, like, see how things are going.

Nicole Paulk - 00:37:57: And we won't complain.

Jon Chee - 00:37:58: Yeah. We won't complain. I'll bring something, you bring something, and we'll—we'll get it fixed. Yeah. Well, Nicole, thanks again. It was so much fun.

Nicole Paulk - 00:38:06: Yeah. This is great.

Outro - 00:38:09: Thanks for listening to this four-part series featuring Nicole Paulk. From hippie farm kid in the Pacific Northwest to a Craigslist ad that dropped her in one of the country's most celebrated stem cell labs, a PhD she calls the most golden years of her life, a postdoc at Stanford, a K01 grant that opened every door, and founding Siren during COVID-19 lockdowns with $6,000,000, no board, and years of unglamorous CMC work she'd do all over again, Nicole's story shows how scrappiness, curiosity, and a willingness to follow the weird paths can redefine what gene therapy is capable of. If you enjoy the show, please subscribe, leave a review, or share it with a friend. Join us for our next series featuring Caitlyn Krebs, co-founder and CEO of Nalu Bio, a company unlocking the endocannabinoid system, the body's own natural balancing mechanism, through an AI-powered platform that designs novel, cannabinoid-inspired small molecules to tackle pain, inflammation, endometriosis, and metabolic disease. Before founding Nalu Bio, Caitlyn spent over twenty years at the intersection of science, technology, and commercialization, building and leading companies across ML and AI-driven drug discovery at Entelos, diabetes prevention at Tethys, Alzheimer's prevention at Neurotrack, and early cancer detection at BlueStar Genomics, completing more than 50 strategic partnerships and product launches across biopharma, diagnostics, and digital health along the way. At Nalu Bio, Caitlyn leads an AI and in silico modeling platform that designs next-generation cannabinoid therapeutics targeting CB1 and CB2 receptors with pharmaceutical-grade quality and scalability and recently announced positive results for a cannabinoid-based treatment for endometriosis, a condition affecting two hundred million women worldwide. With a $12,000,000 Series A and a focus on one of the most chronically underserved spaces in medicine, Caitlyn's journey from seasoned life sciences executive to biotech founder demonstrates how bringing rigorous drug development science to the often overlooked endocannabinoid system can unlock an entirely new class of medicines, making this a conversation 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 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.