NK Cells and Curing Cancer with Nina Horowitz

Welcome to the Axial Podcast. Axial is an early-stage investment firm based in San Francisco. We partner with great founders and inventors investing in early-stage life science companies, often when they are no more than an idea. Axial is fanatical about helping the rare inventor who is compelled to build their own enduring business. Okay, we're recording, Nina. So, uh, we talked for 16 minutes already.

Jeez.

I'm always talking to people. We should record those 16 minutes and do bloopers or something.

But I think this definitely tends to happen with people from New York. Once the conversation picks up its own momentum, it's very hard to stop it.

Yeah, you're very New York and I'm Orange County. So great to talk to you. Kind of some rescheduling here and there, but great to have you on this podcast. Really excited to just hear your story.

Yeah, thank you for having me. This is a platform that I've never had before. This is actually my first podcast interview. So yeah, you have that honor.

I have the honor of— Nia, Nia is a superstar. So everyone, I'm really happy to have Nina Horowitz, a recent Stanford PhD, and who's— what's your title at ImmuneBridge now? Director of—

Head of Research for NK Therapeutics. And by recent, I turned in my dissertation noon on Friday and it is now Monday. So Very, very recent.

Yeah, fresh off the grad school grind, and Nina's actually moving right now, so I'm really excited for her. But yeah, so just to set up, set the table, you know, Nina is somebody who I really highly of in terms of like as an emerging superstar. I think a lot of people agree with that. And so her research is really centered around NK cells and the role of them in cell tumors and understanding how they differentiate understanding how they affect a wide variety of other functions. And so now, kind of a mean bridge, she's kind of bringing her expertise to do a lot of the same work she did in grad school, but then bring them to the clinic, hopefully. And so I'll stop there. Yeah, so let's, let's, maybe you can start off and just tell your story. Where do you want to start? And then go from there.

Yeah, sounds great. So I was always interested in science and reading from a very young age. I was a huge nerd. I was recently looking back through some family videos and my family had gotten me a microscope as a 7th birthday present, which really isn't that common of a gift, I don't think, for a 7-year-old. And I was that kid who would pack my backpack full of books on vacation and read every single one and come back and buy 20 more books at the Scholastic Book Fair. Like, I had this insatiable thirst for knowledge, and then I didn't really have a direction that I was pointing it in at that point, right? Because I was 7 years old. But when I was 8, I became really sick one night and was rushed to the hospital and they found out that I had an ovarian teratoma. And the tumor at that point was already so big that it had torced and I ended up losing my entire ovary. And luckily for me at the time, I didn't really know anything about cancer or how scary cancer was. I had one memory of someone else in my family who had died of cancer, and at that point I had thought it was contagious. So I remembered like being in the hospital, but being afraid to touch them because I thought I might get it as well. And so rushing into the hospital, I had no idea what was going on. And then, of course, by the time I woke up, they were sort of like, it's okay, you're in the clear. We removed the tumor. It was also the early 2000s. So they were like, we removed your appendix as well, just in case in the future you ever get appendicitis, which is like not really something that would fly in this day and age. But they were kind of like, I don't know, the NICU hospital, like we're in there anyways, might as well. So Woke up less one ovary, less one appendix. But I thought like at that point, okay, well, they removed the tumor, the battle's over. That actually was not the case. I ended up, you know, being extensively monitored in and out of the hospital all the time. CAT scans, ultrasounds, blood tests, things like that. But I feel really lucky looking back because my family was with me that entire time. And when I say my family, like not just my mom, dad, and sister who did all sleep in the hospital with me while I was recovering from surgery, But my grandparents, like, I remember my grandparents coming to the hospital with me, with my parents, so that while my parents were sitting with the doctors, someone else could still be sitting with me in the waiting room, like playing checkers or whatever it was. Like, I felt so, so, so supported the entire time. And again, I was pretty much a young kid at that point. I was 8 years old. So I didn't have this, like, you know, scared of the void, like staring death directly in the face type of attitude. I really thought I had escaped scot-free. And then for 10 years I was extensively monitored, but as most things go, teratomas tend to be benign. So they figured after that point, it's okay. Like, we'll stop monitoring you, get a blood test every so often. And then I came to Stanford and I went for my blood tests, whatever, everything looked great, but I had a new OB-GYN out here and she said, well, if you had a teratoma on one ovary, you have a 25% chance of having one in the other. And I don't know why I, with an extensive genetics background, had even thought that that might be the case, but the thought had not crossed my mind. And I went for an ultrasound and I mean, the woman who did my ultrasound, she should get an Oscar, like, or be in the World Poker Tour or something because she— I was like, how's it look? She's like, everything's fine, looks great. Get a call, you know, less than 24 hours later, you have a tumor on your other ovary. So at that point, things were really complicated because now I'm 24 and it's like, do I ever want to have kids? Like, now all I do is study cancer. That's my day job. So I'm really like, looking at the statistics, the mortality, is it going to come back, this and that. Thank goodness my mentor, John, is a head and neck cancer surgeon. So I was calling doctors trying to get an appointment, couldn't get anything. He paged the best surgeon for this on his like internal Stanford system. She called him back right away. He got me in to see her. She ended up being my surgeon. She was wonderful. But before that, I had to go through a round of egg preserving, which was, you know, sort of a hassle. I really don't like needles because of everything that's been going on. I'm a little bit of a tomboy and I found that I was like a hormonal wreck that entire time. Like I went to watch a chick flick with my aunt, Lady Bird, and I was like crying in the movie theater about like, it's so deep to be a mother and all of this stuff. I couldn't believe it, right? I'm like, what a sap. But it was fine. And the tumor was removed and I got to keep part of my ovary. And now I go for an ultrasound every year. It's still the same lady at the clinic. I give her a little bit of crap every time. Like, oh, I remember you. Like, You better tell me the truth this time. But knock on wood, things have been looking pretty good. So I just stay on top of it and I monitor it. And that's sort of, I guess, like the superhero origin story. Like, that's how I got started down this path. But the path has actually been really, really complicated. Like, college was easy. I applied to one college. I got in, double majored in math and biology, did everything that I wanted to do, played the oboe and the bassoon on the side in the Berkshire Symphony. Went to D3 college nationals for ultimate frisbee. Like, it was really a happy-go-lucky time. Everyone's telling me, oh, Nina, you're so smart, you can do whatever you want. Like, winning an award for the best math colloquium at the end of the year. And I'm like, okay, I want to do bioengineering. This is a liberal arts school, by the way. I have a Bachelor of Arts in mathematics and biology. I'm like, I want to do bioengineering. Okay, I'll just apply to the top 5 schools. I had no counseling in this, no nothing. I was like, okay, MIT, Stanford, Johns Hopkins, UC Berkeley, San Francisco, and BU. Right? Like, great choice. I'm sure I'll get into all 5. Rejected from all 5. Didn't even get an interview. And at that point I was like, that was the first time I've ever been rejected from anything in my life. Like, even conservatories— Manhattan School of Music, they took me, whatever. Like, and I couldn't believe it. And that was like, I think like in the moment it was awful, but it actually was really important for me because it's in those times where you have no idea what you're gonna do that you really have to soul search and find that drive to just like keep pushing. And I was like, Well, I actually do really want to get my PhD still. Like, I know that I do. So what do I have to do to do this? So I called the admissions offices, you know, why didn't you take me? I'm so smart, whatever. Had a great score on the GRE, like in my ignorance, thought that was all that mattered, right? If you want to get your PhD in bioengineering, it helps to have taken an engineering class, right? Well, Williams did not offer those. So I got a job at Boston University as a research technician, and I took this program there called LEAP. Late entry accelerated program. So I basically worked 9 to 5 in a research lab. And then at night I took night classes at BU in like thermodynamics, mechanics, circuits, like all of these things that I had never taken at Williams because Williams doesn't have engineering. So worked for 2 years and then I knew the PhD itself was more important to me than where I got it from. So I applied to 19 programs and this is another place where I feel massively privileged, right? At that point I had been working. I didn't have any college loans. I could afford the application fees for 19 PhD programs, which which a lot of people cannot. But I applied to 19 and then luckily got into Stanford, second time's the charm, along with a couple other ones. So came to Stanford and then have been living in this exact room for the last 6 years and will be leaving tomorrow morning by 8 AM. Yeah, but Stanford's been amazing, so I'm glad that I ended up here. Yeah.

We have some pretty sweet posters right now. I have the same Led Zeppelin poster. My favorite Led Zeppelin song is Achilles' Last Stand.

Ah, that's a good one. It's got to be the rain song for me though.

That's a good one too. Okay, yeah, I'm gonna listen to Bruce Springsteen.

Yeah, you're just trying to redeem yourself from that Jungleland.

Yeah, I didn't know, I don't know, I just, I don't know Bruce Springsteen exactly. But, um, yeah, I think for Nina, I think Nina has a lot of grit and I think that kind of comes out in spades. And I think that's kind of why maybe this, your success has come to you despite maybe some challenges, um, throughout that journey. Maybe to back it up just a little bit in terms of like, was that kind of cancer— you also, you know, one thing that Nina's maybe not mentioning but alluding to, she's a very good musician. Maybe could be a world-class musician if you wanted to be, but she's a world-class scientist instead. When you were kind of a kid and going through middle school and high school, did that cancer experience, did it make you focus on wanting to be a scientist? Or when was that moment where you said, hey, I want to be a I want to do science? Was that in college?

Or yeah, it was definitely early for sure. I think this was a big part of it. And music actually is interesting because I was always trying to choose between the two. Like, do I want to go to conservatory or do I want to go to college? Like, the second school I was going to apply to after Williams was going to be Manhattan School of Music for their conservatory. I had written my essays and everything. I had been going there for their pre-college program. Music was always kind of the thing I would do to turn my brain off for a little while. But I find this fascinating because actually a lot of scientists are also like, virtuoso violin players or whatever it is, this like right brain, left brain connection. I think it's, it's really fascinating. And classical music, which I love, is mostly math at the end of the day anyways, right? It's like harmonic frequencies and things like that. So I always did love music and I liked music as an escape from science. But I think deep down I did know from pretty much that early age that science was what I wanted to do because music is fun for me, but science is the way that I can help other people. And so I always knew for sure I wanted to go into science, but I didn't really know what exactly. And then I can vividly remember sitting in my biology class in high school, and we saw a video of a cat that had been engineered to express green fluorescent protein. So it, like, glowed in the dark, basically. And I was like, wow, that is exactly what I want to do. I want to make glow-in-the-dark cats. This is so cool. Like, synthetic biology, you can do anything. So I became fascinated with synthetic biology. So I got to college. I was taking all these classes, right? Synthetic biology, developmental biology, evolutionary biology, game theory, like all of these things that relate and sort of like higher-order ways. And then it was around that time that at BU they started making the CAR-T cells. I believe I was like a sophomore or junior in undergrad when I first heard about CAR-T cells. And I was like, oh my gosh, wait, you can use synthetic biology, this thing that I'm absolutely fascinated with, to cure people of cancer? Like, that is exactly what I want to do. And I knew from then on I wanted to be working with like probably CAR-T cells, or so I thought. And so when I got into Stanford, I immediately fell in love with Christina Smolke. Like, talk about a superstar, brilliant woman, incredible human being. And she had been working on those RNA logic-gated CAR-T cells, which are now— I believe Penn is still working on those. And so I got here, you know, first weekend, everybody's meeting the professors, bright-eyed, bushy-tailed. I'm like, Christina, I think you're so cool. I would love to work in your lab, like, on this project. She's like, yeah, we're shutting the project down, actually. I'm just handing it off to Penn. Like, I'm going to do more of this synthetic opioid generation stuff. And I was like, now what? Right? Like, I came to Stanford being like, I'm going to be in Christina Smolke's lab. Like, one day I'm going to be Christina Smolke. Like, that's my goal in life. And I had even like during the interview weekend, Drew Endy had interviewed me and I had been asking her like, what are the tips on how to woo your wife? Right? Like, how can I get her to like me? Right? And so he was like telling me, oh yeah, compliment her sneakers, this, that, whatever. And I get there, I'm like, throwing all the moves. And she's like, yeah, we're not doing that project anymore. And she's like, shut down. It's like, okay. But at that point, luckily, the field of immunotherapy had grown beyond just CAR-T cells. Right. And there are many amazing advancements that had happened before CAR-T cells as well. Right. Tumor-targeting antibodies, this, that, the other. So luckily her lab isn't the only lab at Stanford that was like somewhere I could see myself. But that was definitely like a shock to the system for sure.

So then, okay, you're— okay, that's a really good line. Stanford science is a way to help people while music is fun. And so kind of a good framework to choose one or the other.

And I have a lot of things that you do, like you can't pour from an empty cup, right? You do have to find the things that recharge you in order to keep helping other people, I think. So I still go to concerts all the time. I love the San Francisco Symphony.

You played the violin?

No, so I played piano, clarinet, oboe, bassoon, tenor saxophone, and a little bit of guitar.

Jeez Louise.

Okay, the nerdiest possible instruments. You should see me on this.

Oboe is definitely the nerdiest. Oboe. Oboe. What a weird instrument.

If this was like a high-end podcast, at this point, instead of a commercial break, you would cut to like some archival footage you had found of like me performing my oboe solos with my husband.

I want to do that too. I think that'd be horrific. But okay, so you're at Stanford and, you know, Christina Smolke. I didn't know about that. I didn't know about that actually. Those dreams kind of vanished within a week. And then you do a bunch of rotations. You rotate, you rotated with Gary Nolan, Crystal McCall, and John Sunwoo, if I remember correctly.

And Ed Engelmann, and briefly 2 weeks in Irv Weissman's lab. So this is sort of a problem I have is like, if it's an important decision, I struggle to make it. Like, I get nervous about making these types of choices. So I really wanted to make sure I was making the right choice.

Okay, those are some heavy hitters. You know, they're all well regarded in their fields. How did you pick John Sonobu of all of them?

Yeah, yeah. So to be honest, Gary was really a left-wing choice for me. Um, I didn't know anything about microscopy or like, you know, multi-dimensional spatial imaging of higher order, whatever it is.. And I figured if I have this opportunity anyways to just spend 3 months in someone's lab picking up techniques, I might as well do something I've never done before, right? Like, what's the point? It's the first rotation. Like, why do something I already know how to do? I should do something new. And at that point, I had been doing cell culture in this orthopedics laboratory and RNA sequencing of human femoral heads, like huge chunks of bone, whatever. I was like, something with computers sounds nice, right? I should say briefly in undergrad, I researched with Joel Dudley back when he was at the Institute for Genomics and Multiscale Biology. That ends up coming full circle later. But that, that was my only experience with computational biology was like a summer in undergrad until Gary Nolan's lab. And I really wanted to like, you know, hone my computational biology skills, learn more about like tissue sectioning, staining, all of that stuff. And I realized pretty quickly that I actually don't have what it takes to be a computational biologist, but I don't think I could have learned it unless I sat in that lab. And watch those brilliant people just code away every single day, these like amazing algorithms to parse together this incredible data. So it helped me in that I knew I didn't want to be a computational biologist, but I did really pick up like his, I don't know, contagious enthusiasm for multidimensional data. And so like ever since then, I've been trying to incorporate CyTOF and CODEX into all the experiments that I do. But I knew I didn't have what it takes to actually be in Gary's lab. So then came Crystal. Crystal, just, you know, talk about someone who I would love to be. That woman is also incredible. And she, I feel like, perfectly bridges this foundational and translational gap, valley of death, whatever you want to call it, in immunotherapy research. And so I researched with her for a while and I loved her. I loved her mentorship style. I really loved her lab, but I knew exactly what I was going to be doing every week, which is like Monday, you seed your cells. Tuesday, you add the DNA. Wednesday, Thursday, Friday, you harvest the virus. The next Monday, you thaw the T cells. You put the CD3, CD28 beads, you expand them, you add the virus, and then you do your killing assay. And then you change one little thing in the DNA sequence, and then you do it again for the next 2 weeks, right? And I was really grateful that I learned how to do that. Like, I use her retroviruses still in my research. Like, that's where I learned how to make viruses and what does it actually take to, like, design a virus yourself. Still sounds like science fiction when we say it, right? I built this virus. Talk about, like, awkward timings of COVID right? I had an uncle who emailed me being like, you guys making your viruses cause this. I'm like, okay, well, I hope you never get cancer because if you do, I'm really about to rub this in your face. Like, but so I learned how to make viruses from Crystal again, like a skill that was critical for me for the rest of my graduate career, but I didn't have before. And then came Ed's lab. I love Ed. I also think he's hilarious. He has been doing immunotherapy since way before immunotherapy was cool, right?

Like, Yeah, yeah.

First one. One of the founders for sure. And this is a bad reason not to join a lab. So people who are listening on the podcast, like early in your PhDs, don't do what I did. But his lab was off campus and there was a really steep hill. I had to ride my bike up every day to get there, and I just didn't want to have to do that. If I was at Stanford, I wanted to be on campus. Like, I honestly wonder all the time, like, would Ed have the Nobel Prize by now if his lab was on campus instead of off campus? I think yes. But you really have to love Ed and his work to be able to give up Stanford and go work at the Stanford Blood Center for 5, 6 years of your life. That being said, I met Shelley Ackerman there. She's been one of my mentors to this day. She was like, yeah, her and Ed both. Ed ended up being on my reading committee. He just signed off on my dissertation 3 short days ago. Like, I have held on to him as a mentor. Absolutely. And I think dendritic cells, like, they're, they're trendy, right? Like, I think NK cells and dendritic cells work really well together. And I'm glad that I was able to study this other branch of the immune system. Firsthand, which I otherwise would not have been able to. When I was there, he was working with Shelley on the antibody drug conjugates that turned into BoltBio. And then I was sort of at a loss because I was like, I don't want to work in Ed's lab. I don't want to work in Crystal's lab. I don't think I'm good enough at coding to work in Gary's lab. Now what? And so I thought the last two people who would be really interesting were Irv Weissman, obviously, like how the name alone, people turn their heads, right? And then I had been going skiing a lot with the Stanford ski team. And this girl named Serena gave me a ride home once. And I was, you know, telling her, like, this is like in the spring. I'm like, I don't think I want to join Ed's lab, but I don't know what I want to do. And she's like, you should join John Sunwoo's lab. And I just, like everybody else, was like, who? And she's like, John Sunwoo. He's a head and neck cancer surgeon. And I'm like, he has his own lab? She's like, yeah, it's in the low-key stem cell building. I was like, okay, well, I'm here in Irvine, like trying to talk to them both anyways. They're one floor above each other. I'll say hi, see what's up. And Irv basically said, you know, the funding that I have is very restricted. For BioEs, unlike the rest of the Stanford biosciences students, you only come in with 1 year of funding and that's it. All the other biosciences get 4. So you're competing directly against these other rotation students and you're going to cost like $250,000 more at least over time. So, you know, Irv said, I have some funding, but it's restricted to this one project, which was like neuroimmunology a little bit. And it wasn't really what I wanted to be working on. And John said, yeah, I'm a head and neck cancer surgeon. I study natural killer cells, but everyone in my lab has the creative flexibility to do pretty much whatever they want. And I said, well, that sounds perfect. And I think from talking to other people who he had mentored, they said, you know, he's the right mix of supportive but not too intense. Like, there's some people in the BioE department who are known to like show up in lab and then they'll text their students like, where are you? You're not here, you know, like that type of thing. And I I wanted to have independence because I wanted to grow into like a really self-motivated, self-sufficient scientist. And I also thought the NK cell work that he was doing was really, really cool. But I started on a project joint with him and Gary trying to do multiplex imaging of T cell receptors in tumors using like tetramer staining. And I spent the first year and a half trying to get this project to work and it didn't work. And it was only then that I sort of came back to the natural killer cells and was like, oh yeah, this is why I wanted to join this lab in the first place. And I think the lesson that I learned there is just because you see it in a paper doesn't actually mean it's true. And if you can't get something to work in your hands in 4 months, you should not keep banging your head against that wall. So I think Michael Fishbach has like a really good course about like how to make good decisions when you're trying to think of like which experiments to prioritize and which questions to ask and things like that. Everybody should take a class like that. Like, I definitely pigeonholed myself way too hard into a project that was either going to work or I was going to get nothing out of it. And that's not a sustainable project for a PhD. So definitely, like, always try to have multiple projects and also try to have a project where, like, even if what you're expecting doesn't happen, you learn something from it, right? All I learned is that tetramer staining is hard. People already knew that. That's why I was doing this project to begin with. So yeah, pivoted from this T-cell project to the—

in terms of timing, this is like 2015-ish, 2016. No, no, no, no, no.

I graduated 2017. So 2016, 2017. Yeah. Early 2018. Yeah. 2018-ish.

This is when, you know, in terms of like the overall field, you know, CAR-Ts had been approved already.

And I remember asking Crystal in the tumor immunology class, do you think people are going to do CAR-NKs? And she goes, no, they're a hassle to work with. Nobody's going to do CAR-NKs.

So like, what was the kind of— so, so you had this kind of initial project that, you know, maybe a lot of scientists see a fancy paper, they go, maybe I can build on top of it. And then you realize there's always artifacts. Should probably move on, and that's a whole other conversation around project design. I'll find the link for Michael's class and that'd be kind of good to add here. But then you make the pivot towards NK cells, and maybe you can give a kind of context in terms of timing, you know, the CAR-T context, and also the context in terms of immunology, right, the two arms of the immune system, and why are NK cells interesting versus T cells in terms of GVHD, and a few other things as well.

Yeah. So, so this will sort of do both at the same time. The context within the field was CAR-Ts had shown early success, like there were some people who were alive who clearly would have been dead if it was not for this therapy. Kids who absolutely would have died of leukemia, lymphoma, whatever it was, and they were in complete remission, like they were disease-free. And they were showing those PET scans where it's like someone's body is lit up with all these metastases and then they're gone, right? But the second wave of that had now begun, which is that either people who had CD19-positive cancer and then received a CD19— anti-CD19 CAR were now coming back with CD20-positive cancer. And also there were those early clinical trials where people unfortunately died from the secondhand effects of the treatment, right? When you give T cells, they basically cause this like massive explosion of cytokines inside your body. And so at first they had been like, unequivocally a miracle. And now they were still a miracle, but there were these sort of like the small text disclaimer, right? This is going to be incredibly harsh, poorly tolerated neurotoxicity, cardiac toxicity, whatever it is. This is a single agent therapeutic. If you have more than, you know, let's say 10 million cancer cells and even 1% of those is negative for the antigen, that's going to rebound. And then starting from thousands of cells, you will now have cancer again. And so I was looking at this, you know, I had fallen in love with immunotherapy because of CAR-T cells 100%. And now people were working working on like, okay, well, so these are the problems. Maybe we can do logic gates or this or that. Right. And I think because of the way T cells work, T cells being part of your adaptive immune system, they're designed to be highly specific, which is good if you want to kill something and it's easy to find, but it's bad if you're going against an opponent, an adversary, whatever you want to call it, that's a little bit heterogeneous. And what I had learned, and I definitely had not appreciated it until I took the immunology course with the med students at Stanford, is that you have this whole other side of your immune system, the innate immune system, which is in itself very heterogeneous and is your first and second line of defense against almost anything that your body could come in contact with. Everything from like helminths through the flu. Right. And so I really started to realize like, okay, people are sort of hating on NK cells, but I think there is something here. There were like whispers going around like, oh, you can put a T-cell designed CAR in an NK cell and it will still work.. And I figured this is something that I think has a lot of potential. And the more I learned from John about the way natural killer cells work, the more I realized like we're trying to engineer all these things into T cells that NK cells are already good at. So NK cells, which stands for natural killer cells, were discovered for their natural ability to kill tumor cells. That's literally how they were discovered. T cells, most of them can't even kill tumor cells or you have to like really strongly activate them first. But NK cells with no prior activation, You culture them with tumor cells, they will kill the tumor cells. And so I realized like we're sitting on a goldmine here, but there are a lot of issues. But what I had to ask myself is like, are these issues, issues that I think other people will be able to solve in the next 5 years? Like, will we eventually be able to culture them better and expand them better and things like that? Because the NK cell field is at least 20 years behind the T cell field. We, we're not even really good at like naming the different subsets. Like T cells, it's like helper, cytotoxic, T resident memory, this, that, Th17, like NK cells are still a mess. T cells, we know exactly which little beads you throw into the culture, they'll expand like crazy. NK cells, the jury's still out on whether or not you can even expand them with beads. But I had to ask, like, if enough people have this same realization that I'm having, and if enough money is thrown at this, are those solvable problems? Yes, absolutely. And so that made me realize, like, this is time to jump ship and just like go full in on the NK cell side of things. And very soon after that is when that Katie Rezvani paper came out in New England Journal of Medicine where she gave mismatched NK cells. So not haploidentical, not from these people's like identical twins or whatever it is to patients, CAR NK cells, and showed really, really good responses at eliminating their liquid tumors.

And some good safety on the follow-up studies.

I think, uh, Oh yeah. They never still often never reach the maximum tolerated dose of these cells. And the other thing that I think is really interesting about off-the-shelf, and this is something that I care really deeply about, having seen firsthand what some of these bills look like, is that the cost of cancer therapies is far too high. I mean, for CAR T-cells, at first it was $500,000. Now we're looking at $1.25 million for some of these like glioblastoma CAR T-cells. Not that I should even be talking because like, didn't Bluebird just come out with a $2.25 million gene therapy, right? Either way, all these prices are too high and financial toxicity is real. Like, I've, I've made decisions about my own medical care. Like, do I want to spend $500 additional now or wait, shift my insurance and then try it again? Right. Like, and that's just like on a small thing. But I can't even imagine having to pay this calculus if I'm like on some antibody therapeutic, $10,000, even if you're only paying 10% of it as your copay, that's still a ton of money. So I think the cost is too high. So off-the-shelf solves a lot of these cost issues. And also the safety thing is huge. That being said, there are some things that T cells can still do that the NK cells can't do. And these are the things that I'm hoping will be solved in the future is if you give someone back their own cells, they will re-engraft in the body and they will have long-term memory against that cancer such that if they relapse again, which of course they're probably likely to do if they were genetically disposed to getting that cancer in the first place, right? It's not just a one-time thing as I've learned myself. Then they should have something already built in to protect them against it again, right? Our lifespans are increasing. Our health spans are increasing. I don't want everybody to have to go into the clinic every year and get a booster shot of their NK cells. I think we should be really prioritizing how can we get at this one thing that the autologous therapies really have, which is the true ability to re-engraft and persist long-term. How can we engineer that into these NK cell therapies as well? So I think that's gonna be like a big, big question in the field is actually, is it maybe better to just get a booster dose every so often and not have them live long-term? Or is it better to actually have them forever? But that, that I think is like sort of a down the road question. In all other facets, NK cells have T cells beat for sure. I think there's a lot of interest in both like the foundational biology, the translational biology, and the biotech side of it on investing in NK cell companies right now. And I've watched the field exploded in the last 5 years. I mean, literally 5 years ago, if you said CAR NK cells, people would laugh at you, and now everybody's talking about them.

I think totally. I think that Versailles data was really exciting in terms of showing just a simple clinical experiment of efficacy and a much better safety than CAR-T.

And also the potential for combination therapies, right? So natural killer cells also have the inherent ability to bind to antibody-coated target cells,. And we already have tons of antibodies in the clinic against various types of cancer. T cells don't interact with antibodies in any way. So you have these, like, natural synergies for combination therapies as well, which I think haven't even yet been fully exploited because it's so complicated to run a clinical trial for a combination therapy, right? Fully agree.

But you touched upon the biggest problem in NK cells. It's like characterizing the underlying biology and all these different subtypes. I think that's what John Sunwoo's lab is really well known for is really going to conferences and saying, hey, we still really don't understand NK cell biology. Full disclaimer, I took a grad school class, immunology, with Dave Rolley. So I'm a little— that's my bias here for NK cells. So just, you know, Dave Rolley is very well known in NK cell biology.

Oh, my favorite coworker in the Sun Woo lab came out of his lab from Berkeley. Yeah, her name was Gail. Gail, shout out to you if you're listening.

Shout out to Gail.

Okay, cool.

We can do shout outs. I love shout outs. Shout out to Dave Arlay. I used to play basketball with Dave before COVID He was actually pretty good. But maybe you can frame the opportunity and the high-level stuff about NK cells and you really talk about the need to map out various subtypes. You're at Stanford, you pivot to NK cell projects. Were your projects related to trying to map out— one big problem you and John map out is Studying NK cells in a solid tumor is a lot different than studying NK cells in peripheral blood. And so, kind of, what were your projects initially related to? Was it something like that or maybe something different and then you moved towards other topics over time?

Yeah. So, I think this is something that I've thought a lot about is like there's theoretically infinite subsets of every type of immune cell, right? It depends what resolution you really want. But one of the reasons that I think we haven't been so good yet at mapping those out is the lack of good techniques. So like CyTOF coming from Gary's lab, I could not have done the work that I did if I was limited to like an 8-color fluorescent antibody flow cytometry panel. So I think like as this data gets better, single-cell RNA sequencing, things like that, we've been able to identify more of these subsets just sheerly because we can look at more surface markers. But the other thing I think we've been missing for a long time is the functional data that supports this subset, right? Some people will say, oh, we found this new type of T cell and it also expresses this. And it's like, okay, well, that's really cool, but who cares? Like, can you show me when that T cell will act differently than another type of T cell that doesn't express that marker? Right? So for me, one of the things that I was working on is looking at a subset of NK cells that expresses two surface integrins on the surface. And, you know, they seemed to be a little bit more cytotoxic and things like that, but we didn't really know, like, are these really different? Like, we were calling them IEILC1-like NK cells, which means they look like this other subset of intraepithelial group 1 and 8 lymphoid cells, but they were NK cells. But then we were really saying, like, do we really need to call this something else just because it has these two surface integrins on the surface? And I said to myself, well, like, we discovered these because we found them in the tumors of head and neck cancer patients, right? So, there's two ways to get into a tumor, active targeting or passive targeting. Passive is just the circulation is like, it has a lot of holes in it. It's very leaky. People call it leaky vasculature. So they just like end up there by mistake. And the other is active targeting in which you are like looking for something that's being secreted by either the tumor cells or the other immune cells inside the tumor. And then there's a lot of other variables there, right? Like how do you extravasate? How do you get from the blood into the tumor and things like that? And so I was thinking like, we keep seeing these in the tumor and we don't see them at all in the blood. So is there some functional difference there between the way that they interact with solid tissue and the way that NK cells from the blood interact with solid tissue? So I designed this tumoroid invasion assay with the help of another woman in my lab, Chen Chen. And basically what we did was we grew miniature tumoroids in Matrigel, which is like a 3D scaffolding from single cells up to visible tumors. Like you could see them with the naked eye. And then I would add either NK cells that were just, they looked like the ones in the blood or these IL-1-like NK cells. And then 2 days later, I would look at the tumors and see which had more NK cells in it. And when I did this experiment, I genuinely was blown away. Like, I think this is probably the highlight of my entire PhD for me was sitting in the confocal microscope room, just looking at these tumors. And they were lit up like, it was like hundreds of NK cells inside the tumors.. And then I was like, well, let me check the controls, right? Like maybe they all did this. And the controls looked empty, handful of cells, 5 cells, 10 cells in the entire tumors. And I realized like this is a massive functional difference, both for foundational, just like fundamental biology and translational biology, right? These cells invade solid tumors like nothing I had ever seen before. And then I went back and I did more experiments to confirm, well, like maybe if you activate the NK cells in a different way, maybe then they do get into the tumor. And just the first time I hadn't activated them well enough. Donor after donor after donor, experiment after experiment, these cells were invading solid tumors like crazy. And so that's when I realized, like, we have markers to identify it and we have a distinct functional behavior. Like, this is a new set of NK cells that I think probably we will be seeing in the clinic. I think this is like a new— in my dissertation, I called it a new immunotherapeutic modality. But I think it speaks to something that sort of had been ignored by the field, which is like, We take these cells, T cells or NK cells, from blood, right? They're circulating immune cells. And then we give them back to patients and we scratch our heads like, oh, that's so weird that not a lot of them ended up in the tumor. Well, you were taking cells that are not designed to be tissue resident and then hoping that they magically become tissue resident, right? What if instead you manufacture them with that tissue resident capacity and then deliver them to the solid tumor? So I think that part's been really cool and it's been cool really digging into this like NK cell biology. I think it's like because the field is still so early, there's all different, like, subsets and everybody has their own names for them and their own different markers that they think they express. And you'll be reading through papers and it's just like table after table with like 17 different markers. But I think what's missing is the functional relationships that go with those. So like we know, like, group 2 innate lymphoid cells are good for helminths, right? Like the big groups we already know, but it's these like novel subsets that we're identifying with like single-cell RNA-seq and CyTOF and all these approaches. That we need to study the functional differences in order to make them useful to other scientists and of course, ideally, eventually to patients as well.

Absolutely. So, I think, yeah, the key theme here is like for any immune cell type, trying to characterize the difference between tissue resident and peripheral blood. And that's kind of something that like I learned from you and John actually, are kind of very, very pronounced prom, is blood, especially for non-T cells.

Well, for T cells as well, because now we're using CAR T cell therapy for solid tumors, right? Like, I, I think it's a parallel approach for sure. And actually, we see these same integrins expressed on the surfaces of T cells, but I think it was ignored for longer in the T cell field because everybody was just treating liquid malignancies, so it didn't really matter. I am actually hoping to see someone mimic exactly what we did with T cells, and I know that it can be done.

Yeah, I think that's also a big reason maybe why these CAR T programs for solid tumors are not seeing success so far. And so maybe we can talk more about the functional experiment we ran and the realities of it. So you talk about it and it all worked out. It's a great Disney— it's a Disney story, but it all worked out at the end. But in reality, how difficult was it to set up that functional experiment?

How many iterations?

Did it take a year? Did it take 3 years? Because that seems to be like a big need.

For every cell type, every immune cell type, how difficult was it to set up that assay? So here's how that experiment works. One month before you're ready, you have to seed your single cells of tumor suspension in Matrigel. And in that part, you have to rush like crazy because Matrigel is cold at 4°C and then liquid, but as soon as it gets warm, it solidifies. And so you have to like pre-cool everything you're going to use in the fridge. So the minute you mix your tumor cells with the Matrigel, it doesn't solidify in the Eppendorf tube. So everything has to be pre-cooled. Then you pass it to your cells. Then you mix as fast as you can. And then you just pipette as many as you can before your pipette tip gets jammed up. Take a new pipette tip. You pipette as many as you can. Yeah, the whole thing's a mess. I'm sweating profusely. Like, it's terrible. There are, I think now people are working on better ways to grow tumoroids efficiently, but this was the method that we went with. Then, so the growing of the tumoroids alone takes a month. So they go from single cells to big cells to big tumors in a month. Then about 2 weeks before you're going to run the assay, you have to isolate the NK cells from peripheral blood. And then you have to culture them in order to differentiate them across 2 passages, changing the media every 2 days. These cells don't care if it's a 3-day weekend. They don't even care if it's 2-day weekend, Saturday, Sunday, I'm in the lab. When, when the labs reopened after COVID hit, I actually had to come to lab 100 days in a row to be getting this data. Yeah, no days off, but it's fine because nothing was happening anyways because it was COVID. So then, you know, you're feeding your cells every 2 days, passaging them. Previously to this, you had to grow and irradiate your feeder cells, by the way, but that's a whole nother story. So then the day of the tumoroid invasion assay, you have to get there 6:00 AM. Start collecting your cells. You have multiple donors who have been passaged and cultured, and you have to keep them all separate. You collect all the cells, then you stain them with a viability dye to make sure they're alive. You stain them with fluorescent antibodies to check their surface marker expression. Then you sit on a cell sorter for 12 hours trying to collect sufficient numbers of each of these different populations from each of these different donors. At this point, it's already 8, 9, maybe even 10 PM. Then you come back downstairs. Then you have to spin them down, wash them in media with IL-15, count them to make sure that you actually have the exact number you need, label them with a fluorescent dye, and then add them to the tumoroids. 48 hours later, you collect all your tumoroids. And then like one by one, you have to like, you know, fix, permeabilize, DAPI stain, and mount them on slides. Then you spend the next 40 hours on the confocal microscope imaging these tumoroids section by section by section. Each tumoroid takes like 6-ish minutes to image, and these experiments were like 100+ tumoroids per experiment. And so like you said Disney princess, and I laughed because I was just picturing myself like I'd be sitting at the microscope like falling asleep, waking up, the image is done acquiring, I'm falling asleep again. I'm like trying to like write my dissertation on my laptop, but my laptop has to be over on the side because I don't want the light leaking into the like the field where the confocal is, like acquiring the images, like the opposite of Disney princess vibes, like literally sitting in a black room. Like I would go and I would sometimes be there from noon until like 6 AM the following morning and I would leave and it would be sunny out. I'd feel like a zombie, like reemerging from underground. Yeah, not Disney princess vibes. But when I realized it worked that first time and when I went and analyzed the data, it lost its tediousness. Then it became exciting because every time I went and did it again and the data looked good, I just knew that I was doing this like groundbreaking assay. Basically nobody had ever showed data like this for NK cells before. So the first one was miserable, but the next one was a little easier and a little easier, but it was massively time-consuming. And again, I could not have done it without the help of Gail, this girl who was working in my lab. Like we would alternate, you know, she would image one donor, I would image another donor, stuff like that. And then I had help as well, like writing the image analysis pipeline, as I alluded to, I'm not the best at coding, but I worked it out. Yeah, so the analysis part was actually really fun. The assay itself was miserable. Like, the two things I'm the most looking forward to are not having to kill mice with my bare hands anymore and not having to sit in a pitch-black confocal room for 12 hours at a time.

Yeah, I think, uh, when was the— what, the first was bad, second got better? What, what, what iteration of this experiment where you finally—

it worked the first time. If it hadn't worked the first time, I'm telling you, I would not even have repeated it.

That's how miserable it was.

First time it worked. Yeah, it worked because, you know, John was saying, you know, this would be cool in theory if it works. Like, John likes to be supportive. He's not going to say that's crazy, it's not going to work. Like, he wants us to sort of like make our own mistakes and things like that. And I showed it, I just like threw some in Matrigel and like just looked at them under our regular microscope that we have in our lab for checking, like, if cells have been transduced and they're fluorescent. And I was like, yeah, they look kind of different. Like, I think it's worth actually doing an experiment with this. And he was like, okay. Like, you know, he wasn't like, yeah, I think it'll definitely work, or like, no, that's not gonna work. But I came back with this set of, you know, 10 tumoroids, whatever it was, and we— he was like, wow, like, if this is real, it's huge. Go repeat it. Which was the correct thing. And then I, you know, quintupled my number of tumors, did it again. It held. And it's— yeah, really after it held the second time, like, that's when I knew.

Cool. Okay. So you have one month of prep and then, you know, how many days of hell?

Oh, a week.

A week of hell. Yeah. Hell, what a freaking— I was dizzy. I just watched Mulan in the morning, so it's Disney on my mind right now.

So yeah. And I came back with those tumor pictures. I'm like sitting on top of the pole, you know, that scene.

I'm like, I did it. You finally got up to 1. Yeah, you did. You did it. You did.

Great.

So you kind of laid out the need to do functional studies for everything, T cells and everything. And you were going to NK cells, which can be seen as like a successor to T cells for some applications. Are there other small things, other cell types that you think are interesting that are worth studying?

Maybe there's so many things that I think are interesting and worth studying.

Because they really have short half-lives?

So I'm going to give you sort of a different answer altogether. Like, so we can engineer cells in sort of 3 different ways internally, right? The cues that they pick up externally, the ways that they respond to those cues themselves, and the cues that they give other cells, right? And I think right now people are really thoroughly engineering all 3 of those things. They're adding chemokine receptors for better tumor homing. They're, they're like alternating like the intracellular domains to increase the speed of immune synapse formation, or they're doing logic gating. So like once they are activated, then they secrete this other cytokine that will in turn like activate the other immune cells. And I think all of that is great, but I still don't think we're at the place that we need to be yet for trafficking into solid tissue. And so where I think the biggest next step is, is biomaterials. Like, I think biomaterials are so cool.— it's another field where we're changing what we're even capable of doing in real time, practically. Like, we're able to fabricate new materials. We can 3D print these, like, complicated structures. And I think biomaterials is really gonna be the biggest breakthrough in, like, safe tumor delivery because you can give way more cells and you're less worried about cytotoxicity cells, by the way, or drugs or whatever it is. And you don't have to be as worried about, like, off-target effects because you're delivering directly to the tumor. So like the last project that's part of my PhD is working on hydrogel delivery of NK cells for solid tumors. And I think one of the reasons I think it's so exciting is like, I look at the people who are doing it, like Sarah Halshorn and Eric Appel, who are just like so brilliant. And like chemistry always kind of like freaked me out. Like I'm not really good at like biophysics and things like that. So maybe part of it is just that I don't get it, which is why they seem really smart, but I genuinely think they are really, really smart. And I think the biggest breakthroughs we're going to see next is not really like which cells, but how are we getting them to where they need to be to have the biggest effect.

Cool.

Okay. I didn't expect that. I hope I don't regret that when I go back and listen in 10 years, you're like neutrophils. I said no.

If someone comes and it's like, car neutrophils, just like, no, I think neutrophils are just cool to study cuz they're like, have really short half-lives.

Yeah.

Oh, they're super hard to study. Yeah. Really hard to study. And then B cells, somewhat interesting, maybe for chronic diseases. Um, but they're hard to manufacture. Um, yeah. And this is why stories, it's more important to tell your story Stories resonate for decades. The actual details of biomaterials and which cell type, you know, that future will unveil itself.

Yeah, and I really think the story of targeted drug delivery is like just beginning, and it started with like those imaging agents, right?

Like those are the first people who really did it. Totally agree. Maybe the one thing we tie it all together is like congrats on getting a PhD. It's such a long journey. And so fulfilling and arduous and so hard. When, when, how did you make the transition to business and industry? And yes, was that year 1, year 4, 1 month before? How did you, when was the spark to say, hey, maybe I should do something in industry?

And what kind of your process and your framework to ultimately, you know, landed at Mean Bridge? So it was the second half of year 6. Like, it was not an early thing. In fact, at first I really thought I wanted to be a professor. It took me getting rejected from NSF and NDSEG and like HHMI and whatever else that I realized, like, I don't like to waste my time writing grants that don't get funded. Like, I really don't like losing. It's not something that I take well. I get really frustrated. I think about all the time I could have been doing experiments and instead I was messing around in Microsoft Word trying to make my word count right and like fit this proposal onto however many pages, which has nothing to do with the science, right? And I was talking to this kid, Tim, who has a company who does— I'm going to get this wrong, but it's basically like bacteria that are better at nitrogen fixation for better crops. He's going to save us all from world hunger, probably. And he just looked at me and he goes, you could spend 3 months on an NIH proposal and it gets rejected. And you could spend 3 weeks putting a PowerPoint deck together and walk down Sand Hill Road and get $5 million. And I was like, oh, you're so right. So right. And so I entered this startup incubator program called Nucleate Bio. And basically what they do is they take people who are in the late stages of their PhDs and have compelling research, and they pair them with business students, and then they go through the program together. And at the end, there's a pitch competition. And I was paired with this girl named Denise, who's an MBA and MPH student at Berkeley Haas. She's brilliant. She knows the science inside and out, and she also knows the business world. And this is so funny now looking back, but like at our first meeting she was like saying things and I'm writing down in my notes like, what is KOL? Like I had never heard that before, right? Like I have to like Google all these things later. Like what is a KOL? What is this? What is that? Right? And she was like speaking the jargon. But once I pieced my way through the jargon, I realized like all the questions she was asking were really, really important. Like what is the regulatory process going to be like? How are, how are people going to get this reimbursed? What's the insurance mechanism? Like, all of these things I think are things that scientists don't always think about. Like, I love fundamental biology. Like, I think all the best advancements do first come from fundamental biology, but then there's this huge gap. Like, they have to eventually impact a patient somehow, and there's a lot of steps there. And so I was like, you know, going through this incubator program and we're working on our pitch deck. And then like, I had great mentors, like Zach Collins, Nick at Innovation Endeavors, Kevin at Cartography Bio. And all of them were like, you know, I actually could really see you in the, like, biotech/VC world. And I had never even considered it before. Like, it just wasn't something— like, I didn't want to— I don't like the idea of people, like, sitting around being like, how much money can we make off people suffering, right? But what I realized from going through these pitches is that actually they are really thinking, like, will this succeed and will this be good for patients? They just have this reality check of like, well, someone has to pay for a clinical trial, right? But it wasn't as bad as I had like sort of made it out to be in my head. And then I realized that I was actually really good at pitching. And then at the end of the whole thing, we won both the like grand prize and the audience choice award for the best pitch at this competition. And people came up to me right afterwards like, we want to invest, we think this technology is really great, et cetera. And that felt really good that I had been able to communicate like something that I cared about in a way that other people who had probably never thought about tissue-resident NK cells in their lives, all of a sudden were really excited about this. And my friends had always told me, you know, you're really good at explaining things. I work as a tutor on the side for a couple students. Like, I, I sort of knew I had that skill, but I hadn't really thought about the fact that that directly translates to this biotech world. And I gave a talk at like the Stanford Immunology Conference, and I won the best talk award there as well. And then I went to this conference for NK cells, and I presented my work,. And immediately afterwards, like, people are sliding into my Twitter DMs offering me postdocs. I had these two people come up to me, kind of wacky dudes. One's bald, the other had a huge beard, and they were like, we want you to come work for us. And I was like, what company is that? And they were like, ImmuneBridge. And I was like, I've never heard of you guys. Like, okay, tell me a little bit more, right? And they're like, we take cord blood stem cells and expand them and differentiate them into NK cells for cell therapy at a comparable cost to antibody manufacturing. And I was like, whoa, that would be a game changer if it worked, right? Like, first of all, just the ability to expand hematopoietic stem cells is like the Holy Grail. And then on top of that, that you could make cell therapy that's actually affordable in addition to being accessible, safe, and effective. Like, that would be huge. And so, you know, they sort of wooed me. Like, Jesse came to my thesis defense, the public session. He brought me a bottle of champagne afterwards. Perrits is messaging me like, let's do this. Like, we would love to have you work for us. And I ended up realizing, like, I could either go at it myself, try to found a company myself, but I would just end up knocking on their door a couple of weeks down the line and be like, can you manufacture these cells for me anyway? So I figured join forces with them. They're both brilliant, brilliant scientists, and they're really, really fun to work with. And so they took me on as head of research for their NK therapeutic division. But they've also, much in the same way John did, they've given me a lot of independence. So I've been leading pitches, I've been reaching out to investors. So Joel now is a partner at Innovation Endeavors who I had like worked under. It was literally 11 years ago that I had been working with him, right? And I got to pitch for him last week and it felt like such an awesome full circle moment to be like, see, you started me on this research path and now I'm actually doing something awesome. And like, by the way, can we have a couple million dollars please and thank you? Yeah, but it's been really fun. I actually think this is definitely, it's It's the Japanese concept of ikigai. Do you know this concept? It's like a Venn diagram and it's how to pick what you should do for your career. And it's like, what's— what do you enjoy doing? What's good for the world and what are you good at doing? And there are the three circles of a Venn diagram, right? It's like if you enjoy doing something and you're good at it, but it's not good for the world, that's just a hobby, right? And if you're good at it and it's good for the world, but you don't really enjoy doing it, then it's a chore, right? So I realized, like, being in this biotech world is actually right in the middle of that Venn diagram for me. It's like, I like it, I think I'm really good at it, and I know that, like, eventually I will hopefully be impacting the lives of patients. And that's really all I need at the end of the day.

That's a great way to end it. I think your— I think entrepreneurship is right up your alley. It accentuates all your skills and powers of storytelling and pitching and scientific rigor, yeah, you're gonna be a superstar like in decades to come. I think ImmuneBridge is the start and you can do really great work there. And then over time be a stalwart in the industry. I think it comes down to like storytelling and you have, in my mind, you're a role model to so many different people, children with cancer, but also scientists who wanna make that transition. And such a struggle sometimes. I think the key thing you kind of highlighted is the jargon can be a little overwhelming. You're so deep in this one way of speaking in academia, or maybe even in— you have scientists who work at GSK or Pfizer, and they're so caught up in their jargon. But then to make the leap into entrepreneurship and just business in general, kind of learning a whole different language.

It's a little tough. It really is. I mean, the first slide deck I put together, all three of my mentors were like, you need to remove— I think the amount was like, 80% of the data had to go. They were like, nobody is even going to understand what you're talking about. Like, you got to give a lot more context, right? Cancer is bad and NK cells good. Just put a couple graphs in there to really sell the point. But that's when I realized, like, I'm so used to going to lab meeting and giving a 60-slide presentation. That's 60 different graphs, right? But that's not how it works in the real world. So it has been an adjustment for sure. But I think it's exactly what you said. Like, the communication is really important. If you have a really exciting result and you don't communicate it well, it's never going to have the impact it deserves.

What are you the best at? You're the best, one of the best storytellers in biotech. I meet a lot of people, and so I think people listening to this will kind of go, oh, Nina's actually— get a little emails from this, probably. People are going to listen to— Nina is so good at explaining things and so good at keeping people engaged. Thank you. And just from my perspective, that's— you're really good at that. And so it's going to carry you forward, uh, and, and, and, and, and So last thing, any, any like final thoughts? I mean, you kind of have, you've been on this journey from childhood to now, you know, maybe the next decade, you know, anything you want to like, you know, accomplish? Do you want to like, you have something in the back of your mind? You want to make a clinical asset? You have something, you have like something you want to get off your bucket list next 10 years or so, or maybe next few years even?

Yeah. I mean, like ideally I want to have had some impact in the clinic. That's always been my goal. I think that, both excites me and scares me because we're really playing God out here with people's lives. Right. And I think that's the one thing that I hope that I can like bring sort of uniquely to this world, which as much as I know they do care, I do still think they can be a little bit disconnected from the lives of patients. I hope I can really bring with me that sense of like what we're doing matters and it's not a money game at the end of the day. It's something that can like change people's entire lives and the lives of everybody who loves them. I was talking a little bit with Thomas at Pillar about this. People are scared to run combination trials because if their drug doesn't look good enough, then they will then have failed the trial. But if they know there's another drug that they could combine theirs with that will actually have some benefit for that patient, and then maybe eventually they want it to be used as a combination therapeutic anyways, I think we do need to be thinking more about the fact that These are real people, right? It's not just a clinical trial with N of 7. Like, that's 7 human beings who have 7 families who love them and people that they love and their own goals and dreams and aspirations. And so, yeah, just hopefully to bring a little more weight to those conversations when we're looking at this, because I even see it sometimes with scientists, right? They're showing a bar graph. It's like a survival curve. And I, and I'm looking at that and I'm like, every time that goes down, that's a human being who just died. And so I really hope I can keep my experiences true to myself and bring a little bit more awareness to the rest of the people that I'm like sort of creeping into their world, that like these are big decisions that they're making and they have real impacts. And I think it's, they all kind of know that like ideally they all want to save somebody's life, right? But I think we do need to shift the calculus a little bit about like the ways that we strategize designing and carrying out these trials.

Yeah, well, that's a great way to end it, Nina. I think we're gonna do a follow-up in like a year or two, and we're gonna, you know, fingers crossed, yeah, it's all gonna work out. But thanks for doing this. I learned a lot myself, something, some new stuff here, and I think a lot of people are gonna find this really useful over the years.

Yeah, thank you for having me.

This has honestly been really fun. Cool. And then good luck with the move. I know the move's gonna be really tough, uh, and so Mugen always thinks, so, but I think it's on to new and better things and doing, starting companies and being part of companies and making drugs. So thanks for doing this again.

I really appreciate it.

Yeah, have a great day.