Episode 13: Launching a Million Rockets

Listen and Subscribe to Inside Cancer Careers

• Apple Podcasts
• Spotify Podcasts

Geraldine Ezeka, Ph.D.

Dr. Geraldine Ezeka is an Associate at Flagship Pioneering, a venture creation firm in Cambridge, MA. In this role, she works with a team of entrepreneurial scientists where she conceives, builds, and grows the science and business strategy for Flagship’s first-in-class bio-platform companies. At Flagship Pioneering, Geraldine is a member of the Founding Team and Head of Operations at a stealth biotech focusing on platform expansion, scientific strategy, innovation, and operation strategy. Geraldine additionally serves as the Director of Funding for VanguardSTEM, a nonprofit that uses STEM as a tool for social justice by creating and disseminating content that highlights women and non-binary people of color in STEM. Within VanguardSTEM, she co-manages a research funding program, titled, Hot Science Summer, where the inaugural program provided funded research grants to 7 women and non-binary persons around the world. 

Prior to joining Flagship, she served as the founding EVP of Culture for Nucleate, a non-profit organization that educates and inspires the next generation of biotech innovators. In this role, she facilitated a seminal partnership between Eli Lilly and Nucleate, initiating the Eli Lilly and Company Genetic Medicine Grand Challenge. She received her Bachelors in Biochemistry and Molecular Biology from University of Maryland, Baltimore County (UMBC) in 2016 and her PhD in the same discipline from the University of Maryland, Baltimore in the spring of 2022.

Alex Kim

Alex Kim is a M.D.-Ph.D. candidate at UCLA David Geffen School of Medicine and the Global Head, Activator at Nucleate.

 

 

 

 

 

Sonia Maryam Setayesh

Sonia Maryam Setayesh is a 4th year PhD candidate at the University of California, where she develops liquid biopsy molecular diagnostic tools for the early detection of breast cancer and multiple myeloma. Prior to joining her PhD, she worked at City of Hope Medical Center as part of a team designing novel CAR-T cell therapies for the treatment of advanced leukemia and lymphoma. Outside of the lab, she works as an investment associate for a private equity firm where she focuses on helping biotech start ups get the support they need in order to grow. She is passionate about helping educate the next generation of biotech leaders and serves as the Vice President for Biotech Connection Los Angeles (BCLA) as well as the Vice President of Partnerships for Nucleate.

 

 

 

Gleb Kuznetsov, Ph.D.

Gleb Kuznetsov is co-founder and CEO of Manifold Bio, a biotechnology company aiming to revolutionize protein therapeutics discovery through novel measurement and design technologies. The company was co-founded with Gleb’s PhD advisor George Church and is focused on creating targeting-enhanced protein therapeutics leveraging its in vivo biologics design platform powered by a novel protein barcoding technology. Gleb comes from an interdisciplinary technical background spanning computational and molecular biology. He completed a Ph.D. in the Harvard Biophysics program combining massively parallel capabilities of DNA sequencing, DNA synthesis, and machine learning technologies to engineer biological systems from the protein to the genome scale.

 

Show Notes

Sonia Maryam Setayesh, PhD candidate at USC: Vice President of Partnerships  
Geraldine Ezeka, PhD: Executive Vice President of Culture   
Alex Kim, MD-PhD candidate at UCLA: Global Head of Activator  
Nucleate 
Activator Program 
Nucleate Summit 
Genesis Program 

Ad: NanCI  

Gleb Kuznetsov, Ph.D.  
Pierce Ogden, Ph.D. 
Shane Lofgren 
Manifold Bio 
BioCurious 
George Church, Ph.D. 
Wyss Institue 

Your Turn: Guest Recommendations 

The Power Law: Venture Capital and the Making of a New Future, by Sebastian Mallaby 
Cells at Work!  
Creativity, Inc.: Overcoming the Unseen Forces That Stand in the Way of True Inspiration by Ed Catmull 
Ten Funny Science Songs that you Need to Hear on Hello Bio: Oliver's favorite "Postdoc Me Now" 

Episode Transcript

[UPBEAT MUSIC] 

OLIVER BOGLER: Hello and welcome to Inside Cancer Careers, a podcast from the National Cancer Institute. I'm your host Oliver Bogler. I work at the NCI in the Center for Cancer Training. On Inside Cancer Careers, we explore all the different ways that people join the fight against disease and we hear their stories. Today, we're talking to early career scientists who are becoming entrepreneurs. First up is Nucleate a student and fellow led organization that helps peers learn about business and what it takes to launch great science into the marketplace. Our guests are 3 members of their leadership team. After the break, we talk to the CEO of Manifold Bio, a new company that was an early participant in the Nucleate program. He took the leap from academia to biotech early in his career and tells us about how that came about. Stay to the end to hear our guests make recommendations and hear how you can take your turn.

OLIVER: In a prior episode, we spoke to Michael Weingarten of NCI's SBIR Center and heard about the programs that he and his team manage to support the early development of discoveries trying to get to market. One challenge they are working on is building a workforce capable of doing that, and it's from Michael that I learned about Nucleate and their work in this space. So it's a great pleasure to welcome three of the leaders of Nucleate to the show. We have Sonia Setayesh, a PhD candidate at the University of Southern California and Nucleate's VP of partnerships, Dr. Geraldine Ezeka, EVP of Culture for Nucleate, and Alex Kim, an MD PhD candidate at UCLA and Global Head of Activator for Nucleate. So welcome.

GERALDINE EZEKA: Thank you for having us.

ALEX KIM: Thanks Oliver. It's a pleasure.

OLIVER: So I'd like to start with learning a little bit about each of you. I'm always interested in what sparked people's interest in science and what path they took to get to where they are right now. So maybe we'll start with you Sonia.

SONIA MARYAM SETAYESH: I did my undergrad in biology, I initially wanted to pursue med school, but after just being introduced in research in my freshman year and understanding the amount of creativity that you could employ with, you know, scientific discovery, it was -- that was it for me. I knew that I was going to pursue a career in research. After finishing my master's in immunology, I went to City of Hope and worked on cancer research and developing and designing CAR T-cell therapies. So it's a type of immune cell therapy that utilizes the adaptive immune system to fight the cancer at City of Hope. And there, it really cemented my interest in pursuing oncology for my scientific career. I then came to USC to pursue my PhD. I work on the early detection of breast cancer and multiple myeloma, and in the beginning of my PhD, I really assumed that there were two types of careers you could have, you could either do research in a lab in academia or you could do the same kind of research in industry in just a much fancier building. So I was really interested in learning more about the different careers that exist, and coincidentally, during my PhD, I was able to discover a blood-based liquid biopsy platform for the early detection of breast cancer. I was very interested in learning about the journey to potentially take this scientific discovery to the clinic. So I was introduced to Nucleate through some of my colleagues and have had just the most wonderful time during the past year being part of the organization and working with partnerships.

OLIVER: Great. Geraldine, I think I, I murdered your last name in the intro. I think even though you just told me how to pronounce it. It's Ezeka, right, Dr. Ezeka. So my apologies for that. Geraldine, please tell us about your own journey to where you are today.

EZEKA: Yeah. So ever since I was a kid, I always told myself that I wanted to be someone that identifies new ways to treat diseases. Coming into undergrad, I thought that clinicians and physicians were those people. So very similar to Sonia, I came in as a biochemistry and molecular biology major thinking that I wanted to go into medical school and become a clinician. It wasn't until my junior year of undergrad that I finally had my first-ever research experience outside of actual class where I was studying HIV in a structural biology lab. And it really opened up the world of science for me. I was able to take the things that we were learning in class and directly apply it physically with the research that we were doing. And for me, that kind of solidified my decision into going into a PhD program. Since I had only had structural biology research experience, I went into a postbaccalaureate research education program after undergrad at the University of South Carolina School of Medicine, and that was where I got my first cancer research experience where we were trying to understand why certain people have a higher -- a higher likelihood of getting HPV-mediated cancer, and we were trying to understand why exactly certain people have those higher propensities for those diseases. That led me to pursue my PhD at the University of Maryland Baltimore with Dr. Richard Eckert, and my thesis project was titled Identifying Molecular Targets of Sulforaphane in Mesothelioma, and mesothelioma is a cancer of the mesothelium, which is a sticky layer that surrounds a bunch of your internal organs. But ultimately, it was super interesting because my thesis project really gave me the opportunity to kind of put to -- give molecular information to kind of ancient therapeutics, if you will, kind of pay homage to how a lot of different ancient therapies use plants and different nature-derived factors have mechanisms to suppress disease. And we were literally identifying those molecular mechanisms and really kind of putting to paper how those different therapies were actually impacting disease. So maybe my last year of grad school or my second-to-last year of grad school, I had a friend who had come. He was also in the biochemistry department, and he was really interested in entrepreneurship. My best friend and I, we created what I -- what we like to call a biocreative company our first couple of years of grad school, not necessarily cancer-related, more artistic and merging art and science kind of using science as an art form. And so, a lot of the people in my like immediate area kind of knew that we had -- knew that I had a lot of interest in entrepreneurship. So I had a really great mentor who was a senior graduate student who pretty much came to me and was like, hey Geraldine. I know that you're interested in this entrepreneurship stuff. If you only stay in the lab, you won't be able to really get to experience these things. So he connected me with some people at Nucleate. He was working at Flagship Pioneering at the time. He connected with me with some people at Nucleate, who had been working with the organization and who had been working at Flagship, as well. I literally emailed one person just to learn more information and they were like, do you want to join us, and I was like, sure. So that's actually how I ended up getting involved with Nucleate, through a really great mentor that knew that I needed to kind of just go beyond what my immediate surroundings were doing and get access to the world of entrepreneurship and the ecosystem beyond, beyond just being in the lab.

OLIVER: Connections can be so important. Alex?

KIM: Yeah, so when I was an undergrad, I studied physics. But I think even then I knew that I was really interested in medicine, and I think I saw kind of this growing vision for how health care could really be revolutionized, and I was really excited to be a part of that in some way that I didn't fully know how to define yet. I guess it went to the others who joined us today. You know, I initially thought I could study physics and really dive into kind of basic scientific thinking, and then go and just do medical school, and I would somewhere along the way, learn how to connect those two together. As I got further along, I realized, oh, maybe just a regular MD program wasn't going to give me the opportunity to do that, and it wasn't until actually my sophomore year of college that I even learned about MD/PhD programs. And I was really fortunate to have a couple of incredible mentors that were able to give me perspective on that and just show me more how research can make such a great impact even in the areas I was thinking about. So then I thought, okay, the MD/PhD program is perfect. I'm going to apply to this program and from day one, when I start, it'll just be a training camp where all the scientists who are working on, you know, bringing brand new technologies or therapies and everything else into medicine will all be working together. I pretty soon realized. Okay, actually, you probably need some more training before you're ready to do that. And the MD/PhD program in all honesty is certainly more -- feels more like you're there to learn medicine, and then you're also there to kind of step away, really do a PhD, and learn how to do science. And certainly, I wanted to learn how to do that. Ultimately, I ended up taking a very kind of basic science choice for my PhD. So I'm now studying basically developmental neurobiology. I became fascinated in cell biology and how, you know, in the future, we could use that for regenerative medicine, tissue engineering, and so on. But the lab I joined and what I'm studying is essentially how specific types of neurons know to connect with the right partners. Hopefully, one day we'll know how to actually program that, which I think would be really amazing. But I wanted to learn how the science worked, how to ask questions about it, really dive in. I've seen my PhD as, I think, an incredible opportunity to get that kind of training, and I'm certainly having a lot of fun. But still I was kind of left with this question of, you know, I did this program because I wanted to, you know, I envisioned that I wanted to work with a team of scientists who are, you know, leading some larger effort, who have a shared kind of grand vision for what can be accomplished and how that can be put into the world, and I was fortunate that I had a close friend. His name is Kevin Dong. He had just started his PhD at Harvard Medical School. I think from the very beginning, he knew what he was looking for, and he got involved with Nucleate in the very early days, and when there's a decision to essentially expand beyond Boston, he basically tapped me and convinced me over a series of phone calls that took several weeks to really get involved, and as soon as I joined, I was just totally in. It was the exact community I was looking for, and the people that I wanted to work with, and so, it's been terrific.

OLIVER: Fantastic. Thank you all for telling us how you got to where you are, into Nucleate. So what is Nucleate?

 

SETAYESH: So I think I'll start and I think everyone can jump in from --

SETAYESH: Yeah, so we are a nonprofit 501(3)(c) organization; we're an equity, free educational programming. So we like to say we are by students for students. So we're almost completely trainee led. So the leadership comprises of PhD students and such as you know, myself, Alex, and Geraldine, and many others that are, you know, come from all around the United States, and now, you know, this year we have actually three international chapters, as well, that we have launched. So, what we started noticing is that in biotech entrepreneurship, in that journey, right, you have, you know, the need for risk-tolerant capital. So there's a lot of VCs, SBIRs, for example, different kind of programs that provide that capital, and then there is you know, the need for real estate. So then there's a lot of incubators/accelerators that provide that, as well. But then there was really this gap missing in social capital. So in order to be able to really translate these projects outside of a lab and into a[JF3]  fully formed venture, teams needed to understand, you know, the pipeline, how that works, how to put a pitch deck together, how to understand not only the scientific questions that they need to phrase and ask properly, but also, putting together a comprehensive business plan. And then how do you network with different investors? How do you get connected with different people that can help you along the way? So once we saw that there was really not many resources that people could go to get equity free, you know, just education on social capital is this is kind of where Nucleate kind of was born out of and what it comes from, and then it really started with the flagship program of Activator where we pair PhD students that have a technology very early stage. Oftentimes it's still in the lab. It's early in its development, and we pair them with MBA candidates that kind of bring that business forward thinking and background to the team. And then once we have that team formation, we put them through a series of seven workshops. And each of those workshops really focus on a specific area that teams need to get feedback on to be able to put a successful pitch deck together. And then, the program culminates in a formal pitch at the end.

OLIVER: Fascinating. So I'm impressed by the fact that it's kind of by students for students. So there, I understand there are hundreds of students involved, maybe even more even in the leadership group, so to speak, kind of all across the US. How does that all work then if you're all -- how do you coordinate your programs? How do you work together?

KIM: Maybe I can touch on that. So, yeah, what Sonia, described and I think she did an excellent job, was an overview of how the Activator program works. Which again, yeah, in the early days was really all that Nucleate does. I think we've grown even larger now, and Geraldine can definitely comment on just the vision for the larger community that we have. So when I started, when I got involved, I basically helped set up the LA chapter, and our goal was to actually reproduce this program, the Activator program, in LA. And so, I led that last year. We had seven really amazing teams and then got pulled in to basically lead that effort this year across all our chapters. So, you know, I think that Zoom has been kind of a hidden blessing that really made all this possible. We work really closely and we're able to do that, you know, across all different time zones and get together because we have these kinds of tools. But really, the way that it works, I guess, is every chapter that comes into the organization that reaches kind of a certain threshold that we're looking for and has done the -- taken the time to kind of map out their ecosystem and really carefully think through how is this program going to work? Who's the network that we can lean on to bring experience into the program, you know, bring mentors into the program and so on? Where are the relationships we need to build? For instance, with our tech transfer offices to be thinking about the technologies that are going through the universities? We're now at a point where that is starting to come together. Each of those chapters starts recruiting both kind of for their leadership team as well as the actual teams that will go through it, which I'd be happy to go into the details of how the program actually operates. But I think we have a central vision, an essentially defined curriculum, and series of workshops that every chapter is going through. You're right that our leadership organization has several 100 people in it as well. I think what's made Nucleate so special and the reason why we're able to deliver this really great program, is like you said, Oliver, it’s truly kind of by students or by trainees and for trainees. And so, we have almost an equal number of people in leadership as people going through the program, because everyone in leadership is equally passionate about getting experience in this space, learning about entrepreneurship, working with, you know, budding startup teams and so on. And so, we're able to put a lot of attention into thinking who would be a great mentors for these teams? You know, who are the great people we could bring in to come and speak with each of these teams? And it's a model that I had to see first-hand to believe, but as soon as I was able to sit in on some of the workshops and see that happen in real time, it's really like magic when you get the right people in the room together.

OLIVER: It's fascinating. Geraldine, you're the EVP of Culture. I guess -- I surmise from that culture is going to be really critical to the success of these chapters and the organization as a whole, right? Can you tell me a little bit more about that?

EZEKA: Yeah. So we define culture as how we all as a unit and as a community kind of think about our values, how we think about our mission, how we think about the attitudes and beliefs that we all share to work together towards a central equal mission. And as Sonia said, an amazing introduction of Nucleate, we simply empower biotech innovators. Our ultimate goal is to empower academic trainees to feel that they can do whatever they want to do in the Biotech Ecosystem, whether it be a CEO. Whether it be a founder. Whether it's venture creation. Whether it's venture capital, and we have all of these educational tools to empower these trainees and academic students to be able to do so. We also democratize access to academic resources so that people who are at a state university or a community college can feel that they have the same exact resources as a Harvard/MIT/Yale/top-name university has to be able to produce whatever biotech interests that they have. So what we do in the culture sector is we really focus on leadership development, but also building community with the external ecosystem, and this looks like a lot of things, as we say that we are the newest innovators of the biotech ecosystem that also looks like innovating how we interact with people. We help -- so Sonia talked a little bit about how at the end of the activator program, we host -- pitch essentially -- a pitch out for all of the different activator participants that are involved in the program. And at the end, we actually held our inaugural Nucleate Summit at the end of last year. And we really innovated on how to make this program unique, inviting, welcoming, but also centering the people who matter in our community most, not the big CEOs but the actual students and the leaders that are a part of our community. So we wanted to really address and kind of speak to their hearts and what would be fun and inviting, but also exciting and still intellectually invigorating for all of the people being welcomed. So we had our summit in the club. Yeah, a 1930s theater turned club in downtown Boston. And then, we had an after party afterwards, and it was awesome, and it was great because one of the co-founders of Gingko [Bioworks], Austin Che walked up to the other Oliver [Dodd] and I and was like “whose idea was it to have this summit at this place?” And it was awesome. So we really tried to think about, try to go beyond what is understood to be normal, what is understood to be professional, what is understood to be innovative. And we try to go beyond what that is and help define who we are in this biotech ecosystem space to really newly define what innovation actually is and what it could be.

OLIVER: Yeah, I mean, why shouldn't things like this be fun as well, right?

EZEKA: Exactly. Why? Why can't things be fun? Why can't we have fun learning with each other? And it was really awesome because on our -- so we had a two-day event. On the first day, it was just a day of shared experiences where people in the biotech ecosystem got to connect with each other through kayaking. We had a beer tour at a biergarten. It was awesome. It just really allowed people the opportunity to first and foremost build communities and then get interested in science together.

OLIVER: I wanted to come back to one of the things that I thought was really intriguing about Nucleate, which is you've already touched upon, I think, Sonia, the matching of, of co-founders, right? The matching of a scientist with an MBA. I mean, that was always intriguing to me because it's not easy to bring people together in a way that works, right? Because there's lots of different axes. They have to have shared interests but also good chemistry and all these kinds of things. So how do you do that?

KIM: Yeah, I would you like me to take this, Sonia.

SETAYESH: Oh, absolutely, yeah.

KIM: The team formation, part of the activator is really crucial to taking someone who has an idea and getting them to the point where they feel like they can actually start to think about what it would look like to turn that into a company or to raise money toward bringing that out of the lab. And I think it's really important because a lot of scientists who are working on an innovative project have never even thought about these concepts. And they're looking for one other person that they need to kind of form a team before they can go into a lot of the other opportunities that are out there. So whether something like Y Combinator, et cetera, they're usually looking that you, you know, you might not have an incorporated company, but they're looking for you to already have a team, but a lot of scientists just can't look left and right and have a bunch of business students that they're already connected with who they can form a team with. So the team formation part of the program takes a couple of months, actually, it's the, it's the first part of the program before you enter essentially the full curriculum. And it's really a chance for business students, which now we've really opened that up. You don't even have to be an MBA student. You can be even a PhD student who's really interested in business. Maybe you've done a fellowship with a venture capital firm, or you have other, some other kind of background that you're really excited to bring to the table, and we have a series of events. I think that, that those networking events are some of the most fun events actually during the program where all the scientists and business track applicants actually get to meet one another, and it's almost like a speed dating event where they essentially rotate through and get to chat with one another. It's really fun, and it's a high energy event and that allows everyone to kind of get to know each other. But I think the other thing that really makes this a good program is that we're obviously totally free, and the Activator is an educational program. So you're not committing to forming a, you know, a partnership, by participating in the program. You form a team, and you are an Activator team and you're going to go through this. You're going to treat it like it's what would you do if this became a real startup, and at the end of it, many actually do go on and become real startups. But you aren't basically committing to that when you agree to go through the program. So it's a great learning opportunity that it's meant to feel kind of with no strings attached. You can really just enjoy the learning.

OLIVER: Alex, that brings another question to mind, which is from what you said, I seem to understand that you don't actually have to have a mature, commercially viable idea or concept yet. I mean, you may have an idea but you haven't tested it yet. At that early stage, you could still benefit from Nucleate.

KIM: Absolutely. I mean, this is a question we get a lot. What I often tell chapters who are newly joining and are about to run their academic program for the first time is basically as a litmus test. You know, ideally you would have patented IP, but you don't need that. Maybe you have proof of concept data, but you don't necessarily even need that. I think the litmus test that I use is we're looking for scientists who have expertise in a field and have an idea in that space. And so, if you're kind of pitching like wouldn't it be cool if we could do this, but you're not the one that actually knows how to do that, then maybe it's not for you. But if you're a scientist in the field and this is your, what you've studied and this is what you really know about and you can actually see a way that this could be done, and you have a real idea and you want to know if it has legs, then this is a great program for you.

OLIVER: Thank you. That's really -- please, Geraldine.

EZEKA: Yeah, and to kind of piggyback on Alex's point, so the Activator program is typically for people that have an expertise for some IP or an idea that has just a little bit of legs to kind of be carried off into the development of actual companies. But Nucleate has several other programs for people that maybe just have an idea that they want to be able to explore with other people. So we have the Genesis program which is like our venture creation program that allows people the opportunity to kind of pretty much ideate around a specific topic and think about innovating in novel spaces. Even if there is no data generated, this is all about ideating and being creative in different spaces that maybe is not your expertise. We also have an Insights Program which is essentially like a journal club, but like a very cool version of the journal club where you get actually sit and chat with the author of the paper who -- and the paper might be the defining paper that launched their company or launched whatever therapy that they are -- that they are pretty popular for. So that's kind of our Insights. And we also have a clinical version of the Insights Journal Club where there are different publications by different clinicians that are invited, and we get to sit and chat with those different people and talk about those publications. So there's a lot of different, while we are -- the flagship program is the activator, we have a bunch of different other educational programs that really unlock the power and the abilities and the different opportunities within the biotech ecosystem.

OLIVER: Yeah, lots to explore. Thank you. Thanks. Sonia, you touched on the fact that Nucleate is now moving beyond the borders of the United States. I'm curious to hear more. You were born in Boston, right? So that's clearly one of the hubs of biotech in the US. But there's so much out there. Tell us about your, your global strategy.

SETAYESH: Yeah, absolutely. So this year, we're actually really excited. We have launched our UK chapter. We have a chapter in France and Switzerland, as well. Actually, our UK chapter this year has been able to source 30 new technologies, I believe, so, and as I was looking through them earlier this month, they're all very exciting and very promising. So as part of our, you know, mission to really, as Geraldine touched on this beautifully, to democratize access, we don't really want to be centered around just the classical hubs where, you know, there's so much information and so many resources that students can go to and learn. But we really want to take this global, and we want to have the approach as no matter where you are, whether it's a biotech hub, whether it is, you know, located in a small rural town in the US or whether it's even overseas, our educational programming can still help you and can -- you can still benefit from it. And as a matter of fact, even beyond the international chapters that we have, we have five teams this year just as part of our global program that are not, you know, associated with any immediate chapters in the US or overseas.

OLIVER: Interesting. I believe you've already mentioned democratizing access a couple of times amongst the three of you, and I'm curious. What is Nucleate's role in diversifying the biotech space? It's not one of the more diverse sectors in the world.

EZEKA: Yeah. So I think that -- I think that it's, it's quite difficult, right? Because I think that, oftentimes, the difficulty for diversifying the biotech space means that we are targeting different institutions, HBCUs, minority -- other minority-serving institutions, community colleges, state universities, universities that you often wouldn't think have access to some of the commercializing your science efforts. Maybe they don't have a venture program within those institutions. Maybe they don't have tech transfer offices within those institutions, but really allowing ourselves to be uniquely positioned in the space so that we almost exist everywhere. So that people who are at these different institutions have the opportunity, not just to learn about other career opportunities that exist within the biotech ecosystem, but then network and connect with people who would actually be able to give them opportunities. I am from a state school in Baltimore, but I am currently an associate at Flagship Pioneering and I only know one other person at my institution who is actually even a -- who's been allotted this opportunity, and I can really say it's because of the network that I was able to build through things like Nucleate, through things like just literally getting out there and meeting people that have allotted me the opportunity to continually, to try to bring more and more people, and I think that we really tried to leave a ladder down in our pursuit. If there is someone that has been given a unique opportunity in the venture creation world, the entrepreneurship world, we're working towards bringing more and more people who look like us, whether they're women, men that are of minoritized groups, of a historically minoritized groups, by bringing them into the fold, bringing them into the new leadership opportunities, developing them as leaders, thinking about how we can develop their careers even further so that they can continue to bring more and more people in their own personal network into the fold.

But also having things like we are hosting a diversity panel. I believe it's next week with several different women of color who are founders or CEOs. Having different opportunities like that, that show that we're not just talking the talk, but we're also walking the walk. We are highlighting and centering these different people. And then also taking it a step further to think about how we can partner with other organizations that center women and non-binary people of color in STEM and thinking about how we can really bring those groups to be in what we hope to be a more diverse biotech ecosystem in the future.

OLIVER: Thank you. That's a great vision. Alex, the last question to you. I think we already sort of touched upon it, and Geraldine just mentioned, you know, trying to involve entities/institutions that, perhaps, don't have a Nucleate chapter yet. What does it take? If we --if someone is listening to us right now and thinks, oh, I really want to get involved now, if they, if they're at a place where Nucleate exists, I guess they can just reach out and connect quite easily. But what if there is no Nucleate where they are yet? How do they go about getting to be part of this amazing program?

KIM: Well, Oliver you are asking a very interesting question and at an interesting time for us as an organization, I would say, because we're really rethinking what it looks like to be a part of leadership, how to really come and join us. And the ultimate answer is that we really want this, like Geraldine and Sonia said, we really want Nucleate to be a global community that you can access and tap into anywhere, and I think there's really kind of two, two schools of thought that we have for how you can get involved. Every year, and this typically happens around the recruitment period, when we're looking for applicants to do the Activator program, we always have a question that says, oh, do you have a technology or are you interested in this but you don't have a chapter in your area? And if they say, yes, then we ask them another question. You know, are you interested in helping set this up in your region? So we are actively looking for leaders who want to step up and start to organize kind of their -- among their peers and their local community, a new chapter, and we're very -- we're very welcoming to that, I think, and we have even now many additional emerging chapters that aren't hosting a full-fledged activator program, but are already brought into the fold, and like you said, make it a little bit easier for the next person who's in that city to get involved. But at the same time, at least I personally think not every single city should be required to run a full-fledged Activator program just to be a part of our network, and we're thinking also just about how that can really be globalized and centralized. So on top of that, I think we're working to just grow our direct kind of HQ leadership community. So if you're listening and you're looking to get involved, you know, I think I can say from first-hand experience, kind of getting us -- a chapter started in your own city is just a really incredible experience. I've never done anything like it per se, and I think it opened a lot of doors, and so it's definitely something to think about, and we do basically poll for that. So look out for that. But also, if you're just looking to get involved and not necessarily take on that kind of grand-scale mission, you know, we have a leadership application, it's open year-round and we basically review it on a rolling basis, and in there listed are all the different initiatives from HQ. You know, we have partnerships which Sonia is leading. We have culture, which Geraldine is leading, we have Activator if you want to come and help me out, as well as my team, and many others. So there's plenty of opportunities to get involved. All you have to do is apply.

OLIVER: And I'm guessing that can happen through your website.

KIM: Yes. Yes. If you go to Nucleate dot XYZ, we should have the leadership application link up there.

OLIVER: Great, and we'll provide links in the show notes. Well, anything that we haven't touched upon that you'd really like our listeners to know? I'll just open it up.

SETAYESH: I think one thing that I really want to emphasize is the community that Nucleate has built. So through this community, not only have I been able to, you know, as a PhD candidate, talk to many CEOs, expand my network, and, you know, especially being part of Partnership and able to, you know, work on everything from sourcing to contracting to alliance management with some of the industry leaders. I've also been able to make friends. I've been able to make friends outside of, you know -- I'm based here in Los Angeles, and I'm very involved with, you know, several different organizations that, you know, do outreach, you know, across the community between UCLA, USC, and Caltech. But after I got involved with Nucleate, I was really able to expand and, you know, learn more about everyone, you know, across the US, and now, you know, that we've gone global even beyond borders. So I think the community that we have built, and just the amount of time and effort that we invest into each leadership member, you know, outside of, you know, our main focus is obviously, you know, our events and our, you know, activator and the different programs that Geraldine touched upon. But I think so much of our time, we also invest in each leadership member, and in cultivating these, you know, long-lasting relationships. And I think that has been just the highlight of my experience and is something I really wanted to touch on.

OLIVER: Thank you.

 

EZEKA: Couldn't emphasize the community aspect any more. I mean, we are a community of people that like to have fun but also get things done as our EVP of Operations, Mani Harb always says, and just like Sonia said, this community that we've cultivated is rich with ingenious people that love to just be creative, bring people together. I know on my team, specifically, we regularly have conversations about what people's career goals are, and how I can help them be uniquely positioned to do whatever they want to do. And if there is any way that I can specifically help or other people within the executive team have the opportunity to help them in any way, we provide those opportunities, and it's been really, really awesome just getting the opportunity very similar to what Sonia said, to get to talk to CEOs and partners at VC firms. To be completely honest, before I joined Nucleate, I didn't know what venture capital was, venture creation, business development. It really just opened my eyes to all of these different career opportunities within the biotech ecosystem. And I think that people really need to be educated on those opportunities, just so that your eyes can get -- your world, can be expanded to what you could potentially do and how you can create real breakthrough in whatever it is that you want to do in your future. So I hope that everyone listening feels empowered to do whatever it is they wanted to do, whether it be research, whether it be coming into the biotech ecosystem as a venture capitalist or a venture creator. And really be empowered to innovate and be creative with your science.

KIM: I would really echo Geraldine's comments. I think that I've made some incredible friendships at Nucleate. It's been an amazing experience and, you know, as a graduate student, it's easy to feel siloed. It's easy to -- I can say that expanding, you know, Nucleate it -- we had pushback here, you know, at times some -- it's easy to kind of be told you're a graduate student, you should just focus on your PhD, and I think it's really important to get the training that you get in graduate school, but it doesn't need to be the only experience that you get, and we're here trying to be brave, you know, really pushing that charge forward. And so, you know, come join us.

OLIVER: Fantastic. Thank you so much and thank you for sharing the great work that you're doing, and I wish you all, each of you, the best success with your, with your future. So, thanks very much for joining us today on the podcast.

KIM: Thanks so much, Oliver.

EZEKA: Thank you so much, Oliver for having us.

OLIVER: All right, we're going to take a quick break, and when we come back, we will be talking to Manifold Bio, one of the companies that has engaged with Nucleate.

[UPBEAT MUSIC] 

OLIVER:: PubMed lists over 270,000 cancer papers published in 2022 – that is a staggering 750 papers every day. It’s great that cancer research is such an active field, but it makes finding the pubs that are critical to your work a challenge. What if you had an AI that paid attention to the papers you read and suggested others as they appear in PubMed? That is exactly what the NCI is building with an app called NanCI. With me to discuss NanCI are two members of the team that are creating NanCI: Chris Perrien of Blue Pane Studios and Duncan Anderson of Humanise.ai.

Chris, you’ve been building apps for NCI for over a decade. What is new about NanCI?

CHRIS: Fundamentally NanCI represents a shift in user experience – in the prior generation of apps people had to know where to look to find things. Now, they can find the information using AI agents. I think of NanCI as a friendly research assistant who makes suggestions and answers questions. Of course, it is early days, and NanCI is still learning from their users, but they will get better and better over time. 

 

Duncan, you bring AI expertise to the project. Can you tell us what capabilities that brings to NanCI?

DUNCAN: NanCI is all about connecting scientists. Right now the focus is on connecting them to papers relevant to their interests, which NanCI does by matching vector representations of abstracts and looking at co-citations. If you tell NanCI that you find a group of papers interesting, by bookmarking them, the app will keep an eye on PubMed for you and suggest related publications. You can also share these folders with colleagues and export them to your reference manager. You can read the paper right there in NanCI, and follow any author to see when they publish preprints. Down the road we intend to help people network based on shared scientific and career interests. And much more – these are just some of the features coming to the app. 

Thanks, Chris and Duncan. Right now NanCI is available in the Apple app store, and it will be coming to android later this year. Download it and give it a try! Your feedback on NanCI is very welcome – you can send that to us here at NCIICC@nih.gov.

 

[UPBEAT MUSIC]

OLIVER: And we are back. It's a pleasure to welcome one of the cofounders of Manifold Bio to the pod, a startup that's connected with the Nucleate program we just heard about. Dr. Gleb Kuznetsov, the CEO, welcome.

GLEB KUZNETSOV: Thank you so much, Oliver, a pleasure to be here.

OLIVER: Before we hear about Manifold and the Nucleate experience, I'd like to ask you to tell us a little bit about your career path. What led you to become a scientist?

KUZNETSOV: Yeah, my career path was interesting, you know, it wasn't the standard undergraduate science degree into PhD degree, et cetera. I actually had an undergrad in computer science, believe it or not. So I went to MIT as an undergrad, came there, never, you know, I took AP Biology in high school and so had basically tested out the requirements. And believe it or not, I took all engineering computer science classes throughout, was really interested in robotics, was really interested in, had some tangential interests in hybrid vehicles, in artificial intelligence. And it was actually in my final year of undergraduate where I took a bioinformatics class as a sort of final credit. And that was actually this interesting moment for me where I realized, you know, this is 2010, we've just got 40 mammal genomes sequenced, so just to kind of date that moment in time. And part of our class, this was Manolis Kellis' class. He sort of had, we had dibs on taking a stab at what patterns we could find in these sequences. It's, for me, diving into those DNA sequences, looking for those patterns, understanding evolution through the lens of this new up and coming DNA-sequencing technology was super-exciting for me. And so for me, I started reading a lot in my spare time about biology. I went on, became a software engineer at Google for about a year and a half after undergrad. And still continued to have in the back of my mind how interesting biology was, I attended a space called BioCurious in San Francisco as part of a DIY hacker space--

OLIVER: Interesting.

KUZNETSOV: --for learning about, they'd have post docs give talks, we would do some very basic experiments like taking a green fluorescent protein gene and putting it, transforming it into E. coli and watching the E. coli turn green the next day. So these sort of assembly of experiences motivated me to do what, at the time, my parents said was quite an irrational move, which was to leave my well-paying job as a software engineer, reach out to some labs, one of them was George Church's lab, and just take this leap, where I showed up and started working helping out as the computationalist and understanding what, you know, starting to learn about biology. And there's actually a lot of transformations, I had a lot of realizations from there.

OLIVER: Yeah. And then you, in Dr. Church's lab, you switched from being, as you say, a computationalist to doing a PhD with him in synthetic biology, I guess, or something related to that.

KUZNETSOV: Yeah, exactly. It's funny, my personal hypothesis coming to George Church's lab was I could come in and help people build software, maybe I could help automate experiments, you know, maybe the naive view that some engineers have externally, I had this, which was, biology is inefficient, it's old fashioned, people are doing things manually, you know, with the power of compute and AI and whatnot, we could transform it. But the interesting thing is I came to appreciate the nuances of innovating in biology. You really have to start with low, non-scalable approaches, really understand the fundamentals of what's going on. It also opened me up to a different approach to biology and actually a different approach to engineering that's unique to biology and synthetic biology, which is this idea of multiplexing, or being able to measure many molecules, many molecules, many designs simultaneously in mixture. It's very analogous to how evolution happens at the molecular level. You have RNA, there's sort of an RNA world at some point, molecules bouncing around, the best ones survived and replicated. Eventually, proteins appeared on the scene, eventually cells. And so we kind of, in George Church's lab where the teams there, the people there were innovating in that way, leveraging DNA synthesis technologies to be able to actually build the constructs and sort of push and guide evolution and engineering. So that's, you know, synthetic biology, for example, has a lot of definitions, a lot of different ways, that's sort of the flavor that I really got into is this DNA synthesis coupled with DNA-sequencing in these sort of design-build-test cycles of experiments, so building many different protein or genome constructs, testing them, competing them, measuring what happens, and then closing the loop. So I got, you know, very interested in that kind of approach, learned experimentation, learned how to design experiments and how to execute them. And sort of my PhD was focused on everything from genome scale to protein scale. And today, there's a lot of the elements of that that's gone into the company into Manifold Bio.

OLIVER: I just wanted to probe a little bit deeper. So synthetic biology, the protein mixtures, or nucleic acid mixtures, those are not exclusively naturally occurring entities, these are also entities that are new?

KUZNETSOV: Yes, so what's so cool and what's so powerful about the kinds of technologies we have today, so, you know, we talk a lot about DNA-sequencing and, you know, in 2010, 2012, when I was starting out in the field, it was very much about reading genomes, or mostly people were thinking about reading human genomes, and how that's going to translate into health. But in George Church's lab, it was about reading the output of many different experiments. And the way you can generate those experiments is you can actually design, many specific protein sequences that you want to test. And specifically, you can order the DNA that codes for those. So already in 2010 or 2012, when I joined Church's lab, it was pretty standard, at least in his lab, to be able to send a spreadsheet with 100,000, or a million DNA sequences encoding for that many proteins you want to test. And you would start with natural sequences, but then you could introduce mutations. And already at that scale, you could potentially search the space of every single mutation or every pair of mutations to a particular protein, and really start getting at the nuances of how these systems work. And there's this approach to engineering, which was so unlike anything that's really possible anywhere else, you know, just drawing a comparison, when we build, when folks are building rockets, you sort of get one shot at a time. You have to build the one rocket, you better hope it's right. There's so many pieces that could fail. It's very expensive to launch and you have this will-it-fly [CG4] [OB5] moment. The advantage you have there is we understand the physics at that macroscale a lot better. Biology physics, it's this physics of complexity, and it's much more complicated to understand. But we don't have to build one rocket or one protein at a time, we can build a million at a time, and sort of and launch them all simultaneously very inexpensively, and see what works. that to me, is at the core of synthetic biology, just build things, try them out, and then learn from that data and then continue.

OLIVER:  See which ones make it off the launchpad, that's very, that's a really good way of thinking about it.

KUZNETSOV: Many of them blow up[CG6] [OB7] , which is fine, as long as a few go up, then you have a starting point. And you also learn from everything that didn't work.

OLIVER:  So I'm curious from a career point of view, being an engineer and a computer scientist, coming into biology, how do you think your perspective of biology sort of differs from someone? I think your CSO came a more traditional path, right? He went through a sort of biochemistry/molecular biology-type path. How do you complement each other in terms of your scientific worldviews?

KUZNETSOV: Yeah, it's very interesting. So my CSO, Pierce Ogden, we met basically the first day of graduate school, very talented, brilliant scientist. So he indeed came from a more classic molecular biology-type background and undergrad, he had spent some time in a few labs in UCSF, between Jim Wells' lab and I think Brian Shoichet, and I think the Wells' lab was about empirical high throughput automation and testing, so sort of robotic-type testing. The Shoichet lab was more about virtual screening and docking-type experiments. And Pierce's role as sort of in between undergrad and grad was to try to combine and find integration between those two sides. And the interesting thing is, he was attracted to the Church lab because he had read George Church's book, which was talking about this idea of multiplexing, where instead of doing experiments one at a time and maybe scaling them by automation and robotics, you could just build these mixtures that compete them in small reactions, again, much closer to evolution. And now to do that, you again, bring this sort of, you have to have a computational design edge. So Pierce came over to the George Church's lab, he had already started taking some bioinformatics class, and as we teamed up, I started sort of transferring knowledge to him of good robust software and computational bioinformatics practices. From him, I learned about how to think as like a molecular biologist, how to design experiments and it became this really nice relationship where, you know, I was thinking very much as an engineer of how to kind of structure experiments, testing, et cetera, while Pierce thinks a lot more like a biologist, about the fuzziness, and everything. And together, we've sort of merged in the way that we think, and continue to be very complimentary, and very productive collaboration that now almost has lasted 10 years.

OLIVER:  So take us through the moment, if you would, where you decide to launch Manifold Bio. You're finishing graduate school, correct, right? And you've chosen not to do a post-doc.

KUZNETSOV: Yeah, so I can take you through that time. I wish I can say there was an obvious moment where we woke up and said, "Let's start Manifold Bio." But you know, it's a little bit more of a journey. I think about halfway through graduate school for Pie rce and I, maybe around 2016-2017, we started working more closely together on various experiments. And critically, we were really excited about the potential of bringing these really interesting multiplexing methods that can really push the throughput and the measurement capacity of what you can do with engineering proteins. And so we were quite excited, especially about the space of antibodies. So antibodies are very useful, obviously, they are the body's natural immune system. They've been now sort of industrialized to be become both reagents as tools for measuring biology. They've also become drugs for actual therapies. So Humira was, I think, one of the first ones commercialized, very successful drug. And then, of course, many different oncology-based antibodies, a lot of those spanning, you know, the early days of Genentech. And today, of course, I think there's over 100 approved antibodies and many hundreds or even 1,000s in clinical trials. And so we're really excited about the potential going that direction. And as we were wrapping up our PhDs, we were starting to experiment with new methods of creating antibodies. So our idea was, rather than raising antibodies the traditional way, which, you know, there have been a few different approaches there, there's been, of course, immunization, so you know, taking an animal, immunizing it with an antigen, pulling out/purifying the B-cells, and ultimately, the antibodies that are reactive there. There was other methods with display technologies, phage display, use display, et cetera but all of them kind of have this approach of screening against a single target. We were quite excited about could we raise antibodies against many targets simultaneously and, specifically, not just targets but even components of those targets' specific epitopes. And we had this concept of how to do this, we started prototyping this in the lab. We are fortunate, so the Wyss Institute is set up, the Wyss Institute portion of Harvard is set up as a translational Institute. So it's actually not an unusual pattern for graduate students as they're either during the grad school or even wrapping up and sort of transitioning post-doc to sort of have a shot to try to translate some of their work, and have a little bit of extra time there. So I graduated 2018, I had an extra year or so of doing some more experimentation. Pierce, likewise, had a similar timeframe. And so, in addition to that experimentation and proof of concepts, we also had time and space to go out and talk to folks in industry, so that was really, really important. So we went out and talked to antibody engineers, leaders in the field in big pharma companies and biotechs, entrepreneurs, as well as clinicians and academics and really tried to understand the problems, the white space that was out there. And we came to appreciate that, you know, just having a new antibody discovery technology in itself was not, you know, by itself was not going to be potentially enough to set us apart. It could be something special, we could pick one target and pick one drug and go for it, it's kind of like everyone else. But in those conversations, we came to appreciate that there's actually other parts of the drug discovery approach that were pretty big bottlenecks. In fact, such big bottlenecks that folks wouldn't talk about them as maybe this is a problem you can solve but would talk about them as "Well, your technology is good, but you're going to hit these challenges that we all hit anyway." So you know, kind of "good luck" or "just FYI". And so for us, being engineers, liking to really not just, you know, we wanted to come in and were interested in therapeutic discovery but we're also interested in challenging the paradigms and really changing how things can be done, especially if we could open up new opportunities, new possibilities. So we got really excited about these bottleneck points. So some of these bottlenecks are these functional tests. So the drug discovery workflow starts broadly, you have many possible molecules early on, you start characterizing them in vitro, you funnel in further, you do optimization based on those in vitro tests. And ultimately, you have, you start to actually look like that will-it-fly moment for a rocket where you have a few molecules. You're going in vivo, you're hoping that you get the efficacy, you know, for example, shrinking a tumor in a mouse, you're hoping that you're going to get the safety, so making sure the molecule is not causing a systemic effect, is going where it needs to go. And these were very low throughput steps. And this is sort of this bottleneck, this constraint was what really started inspiring us to bring what we've always been good at, what George Church's lab has trained us to think about, which is how do we take a low throughput problem and make it high throughput, being able to test things. And here's especially for something like in vivo testing, which is a really big bottleneck, you can't really bring automation to solve this problem, because you can't just scale the number of animals you can use, both for, of course, ethical reasons and financial reasons. But what you can potentially do is you can test more molecules at a time simultaneously. So this was the sort of origin of that invention, which was the core for us, this protein bar-coding concept. And so that started ruminating in our minds and this is sort of the point of just before we had, in retrospect spun out, there's this big question facing us, do we try to build this technology in the labs sort of as post-docs, or do we spin out and  just trying to start a company and do it ourselves?

OLIVER: Interesting. So what you described just a moment ago, where you and Dr. Ogden were sort of taking a landscape survey of the field of antibody engineering and think, that sounds almost like moving into business, into entrepreneurship, right? Was Nucleate a component of that? Did they help you with that? Is that an experience you have that helped you plan those activities?

KUZNETSOV: Yes, so Nucleate was a really important catalyst for our sort of transformation from scientist into entrepreneurs. So the timing for Nucleate came around, we did it in early 2019, so Pierce was finishing his PhD, I had just finished a few months ago. And the interesting, so this is going to be the first year of Nucleate and at the time, it was called Activate. And so it was a very small program, it had just been created by Soufiane Aboulhouda from George Church's lab, and Marissa Pettit, who was an MBA student at the Harvard Business School. And basically, Soufiane came to us, he was working a few benches away, and asked us, "Hey, we're going to do this program, you guys should do it. It sounds like you have this company idea." And our response was, "I don't know, we want to sort of keep tinkering in the lab, we were not really sure what we will do." So credit to Soufiane, he kept coming back every few days and saying, "You know you guys should really do this program. I think it'd be good for you, you'll have some reps of, you know, creating a slide deck, will bring you in front of folks, you know, experienced biotech company-builders and entrepreneurs and give you some feedback." So, you know, we warmed up to the idea. We thought, "Okay, maybe we're a little early here, we don't really have our science ready. But you know, let's do it, it can't hurt." And again, Soufiane, you know, to his credit, this is why this organization has become so big and successful is Soufiane is a very talented, persistent person. And of course, working with Marissa, Marissa's super-talented, organizational person and, you know, sort of the history speaks for itself what happened there. But yeah, so we joined Nucleate. It really provided the pressures and the education to go through all of those first reps, our first slide deck, our first operational budget plan, our first sort of mapping out therapeutic indication areas and all of these were done with feedback from really talented folks, you know, folks from RA Capital. We had, I think, we had a chance to speak with investors, one from 5AM, Jamil Beg, another one from Atlas Venture, Kevin Bitterman, so, you know, folks that have built, you know, very impressive companies. And so really, you know, got a lot of feedback and sort of closed the loop there. And by the end, we had an initial story for Manifold. And, you know, that was really is the foundation, you know, our deck a year later, when we raised our seed was not, you know, tremendously different, the core story had been formed there.

OLIVER: So the science and this entrepreneurial component kind of came together in a great way. And is that, the timing of that seems to have given you the confidence not to go the traditional post-doc route, staying in the lab, but actually taking another leap here into the private sector. What was that like? How did that feel?

KUZNETSOV: Yeah, so I think, after doing that, it was really exciting, because all of a sudden, we started to see by starting some of these business development-type activities earlier, they started influencing and driving our science in a good way. We started realizing which experiments to prioritize, how to think about risks, how to communicate those risks and so that was quite important. So sort of the second half of 2019, we kept, I don't think we had the full concept of what Manifold would become but now we had sort of different kinds of de-risking on our mind. And also, it sort of did start to reduce to practice, what were the pieces that we needed to put together. We had a sense of what investors were going to be thinking about, so those, yeah, all those key pieces, were there. It also motivated even further customer development, going out and talking to folks, getting feedback and closing the loop, you know, a pattern that continues to this day. That's kind of part of my role is part on the science and part going out and continuing to stay engaged with potential pharma partners, with experts in the fields and prioritizing what we're working on internally and what we could be doing together with folks outside, and that all started there with Nucleate.

OLIVER: So give us a snapshot of the Manifold Bio today. It's how old, four years, three, four years?

KUZNETSOV: Yes, so we officially spun out of Harvard in May 2020--

OLIVER: Oh.

KUZNETSOV:  --so at the time, that was basically myself and Pierce and our other co-founder, who had just joined us, Shane Lofgren, so he heads business development, he'd previously been a bioinformatics scientist who sourced and built a company with Atlas Venture. So he brought a little more of that deep therapeutic experience, especially in the oncology space and that really, you know, brought us into some of our old core internal initial applications in cancer. And so that fundraise happened, believe it or not, right as COVID was setting in, we were still debating "Do we want to do more de-risking and maybe stay longer as post-docs at Harvard? Or do we want to spin out and take a…, see what we can do?" We were leaning towards spinning out because the conception of what it would be required to do was more of a engineering-type risk set and we were very confident and had a good track record as engineers and so we were less concerned that there would be sort of some biology that would appear and trump us. And so we started that momentum, still not sure. And then in March 2020, of course, the world shut down, the labs shut down. So all of a sudden, we had nothing to do except sit there and think and talk to people on Zoom, as we all did for a while. So in that moment, we started, you know, continued conversation with investors, and spoke to a number of folks and sort of pushed through the inertia and confusion that was happening in that time, and found some really supportive early investors who liked the concept, liked the team, and we raised a $5.4 million seed, and sort of gave us a shot. So that was the beginning there, you know, and, you know, fast forward today, it's now about three years later, we recently raised a $40 million Series A.

OLIVER: Congratulations.

KUZNETSOV: Thank you. We are 24 people growing, you know, another, continue to grow the team very carefully and gradually, importantly, to maintain that long horizon and continue to make really good progress. And, yeah, we have a beautiful lab here in Fenway, not too far from, actually the Wyss Institute is going to move in, they've had to change buildings, so they're going to move into the same building as us. So that's going to be really fun.

OLIVER: So when you say, Fenway, are you close to Fenway Park?

KUZNETSOV: We are close to Fenway Park. Today is the opening day of Red Sox as well, so we can actually see the, we can actually see the Jumbotron and almost into the park, so it's a beautiful lab for folks ever come visit us.

OLIVER: That sounds great.  What can you tell us about the work that Manifold Bio is doing and you've had M code, this is the bar-coding technology, you're selecting active proteins in a variety of assays. You mentioned oncology, is that an area of focus for you?

KUZNETSOV: Yep, so for Manifold, so ultimately we're making antibody-type therapeutics, so not just monoclonal antibodies, but also more complex format multi-specifics and drugs that have been very interesting but challenging from an engineering standpoint. And what our many advantages and many different places we're investing from a technology and platform perspective, our core platform is this protein bar-coding approach. So this is where we overcame, this was our invention that addressed that bottleneck we saw in the field, which is that low throughput fixed state that all drug programs reach when they get to sort of further functional or in vivo testing. And the insight that we had was for many drugs, you know, especially in oncology, but for many different indications, the challenge is how do you get a drug or a, you know, a very toxic payload to deliver specifically just to the tissues and cells that are cancerous, and avoid all the other healthy tissues, so really getting at the core of a key aspect of that therapeutic window, you know, having action only where you want it or more pithy way we like to describe it as getting the drugs to go where they should and not where they shouldn't.

OLIVER: It's important.

KUZNETSOV: And so, yeah, and so if you have a way to have a quick feedback cycle of testing a molecule actually in that complex in vivo environment, of not just getting to see how well it gets to a target, but how well it overall navigates that complexity of a 3D mammalian environment, you know, that's something that's really hard to replicate in any kind of in vitro system. And so critically, you want to do that for many molecules at a time, since every in vivo test is quite precious. So we built this protein bar-coding technology. And the way to think of it is it's an extra bit of protein, like a protein tag, think of like a FLAG-tag that folks might be familiar with, with some of their assays. And that tag, all of a sudden, makes the antibody or drug trackable. And now given a mixture of these tags embedded in tissue, or sorry, mixture of these tagged drugs embedded in some tissue and sampled from the animal or embedded in or in the blood sample, we can take that sample, we can, with our proprietary platform, quantify the relative and absolute abundance of those different drug entities, and basically get a snapshot for hundreds of drugs in parallel, which ones are specifically ending up where they need to be, as well as which ones are ending up in other areas where they should not be or which ones are just having poor compatibility with the sort of challenging environments of in vivo.

OLIVER: So will this technology enable you to target proteins, for example, that have historically been hard to target?

KUZNETSOV: So where we actually focus, and this is sort of from our kind of customer business development knowledge and strategies, is we're actually thinking about areas where these are targets that have been well known. We know if we target them, they can be very efficacious, the tumors will definitely shrink. But the challenge has always been one of toxicity. These are often targets that are very prevalent elsewhere. And so we've seen tests in clinic, where it's really challenging. We start to see high toxicity, sometimes even patient deaths, when you start to increase to a dose, when you start to see that efficacy. And so by really focusing on that challenge that those molecules, those targets that have had these clinical challenges, and bringing our approach and then bringing novel protein designs paired with our measurement approach, this gives us, what we believe, is a really big advantage to take on some of these targets that, classically, many of them basically have been labeled as intractable and our goal is  to make them tractable and do that through our technology edge.

OLIVER: So the biology of the target is well enough understood to make it validated but you're going to be in a position to actually take advantage of that.

KUZNETSOV: Yeah, exactly. And that's sort of the first version, you know, as an entrepreneur, you have to be disciplined in terms of the applications and the staging. You know, we're also thinking about targets that are less understood, and, or even new targets. So we're also quite good and have a team of folks that can do bioinformatics and target discovery-type work. And so we have lists of targets that are less well understood. And again, where our technology comes in is, it could be risky as a new entire program to invest in. But because we can reduce it to some of those critical tests, as you know, into the most translational systems, we can get into short of humans and we can do that quickly and efficiently with relatively low capital, all of a sudden, we have an edge as well to try to attain some of these more novel targets as well.

OLIVER: A quicker point of failure, if you will, for something that is a new target, unexplored target.

KUZNETSOV: That's right and that's super important. As a startup, you want to really learn quickly and make decisions as quickly as possible.

OLIVER: Yeah, it makes total sense. Well, thank you very much. I did wonder, your career path is so interesting, what advice would you give to our listeners who are fascinated, not only by the science that you do, but also by your decision and that of your colleagues to sort of go into the entrepreneurial space?

KUZNETSOV: Yeah, there's, you know, it's one of those things that, in retrospect, it seems like maybe you've made some of the right paths and decisions and maybe it's clear where things can be more efficient. You know, I just reflect on my own experience. I think there's a common pattern of following my curiosity was one key pattern. So just if I, you know, I became really interested in biology. I sort of thought "Wow, this really could be transformational, kind of this new DNA-based lens into the natural world." And so I think just recognizing if something makes you super-excited, and you're also positioned, you have some resonance there, I was a computational, trained as a computationalist, so I could immediately start playing with computational data as sort of a low barrier to entry in that way for me. I think that was important. I think a second thing is also erring on the side of when you have sort of an option between more of an engineering or applied-type opportunity, whether it's a job or an academic program, versus something that takes you more down the path of business, like unless you feel saturated on the engineering and the science and learning, I tell people to err on the side of choosing that path, staying more hands-on. Even before I took my job at Google, I had one job offer that was more of a product manager that would have been less technical at an exciting startup or the opportunity was to go to Google learn from the best to how to be a really good computer scientist, good software engineer and I chose that path. And I chose that path when I chose to go into biology and even as a computationalist in the lab, I chose the path of learning to do experiments and I kept sort of choosing the more technical path until almost the opportunity, the need from a business perspective became such that it had to shift to other things, I had to start thinking about the business, start thinking about operational. But now so I have so much knowledge and experience coming from my time as a technical contributor, as a scientist, as an engineer, that it gave me the context and credibility to be able to do that work and to build teams. And the last piece of advice is really to be looking around at people around you and constantly trying to find the best people to work with. So I've been very fortunate, maybe the most intentional thing of my path was paying attention to people around me so when I chose to come to George Church's lab, it's because I'd spoken to a few really talented scientists there, Mark Lajoie and Jon Goodman and I could just tell they had a good vision of what they wanted to do. They had a clear vision of how I could help them and they would be really good mentors to me and also, eventually, really good colleagues and teammates. And then likewise, I started working with Pierce Ogden and Pierce Ogden, you know, is one of the best collaborators I've had in my life, obviously, and just the resonance there and the complimentarily has been super-important. So those three things, I think, are the key, you know, follow your curiosity, err on the side of doing and engineering science as long as possible and really pay attention to teams around you and curate that and, you know, keep seeking that, never turn that off.

OLIVER: Well, thank you so very much, Dr. Kuznetsov, that's fantastic advice and I wish Manifold Bio all possible success. You seem to be on a very exciting journey and as a cancer survivor, myself, I hope you develop all kinds of fantastic new agents to help patients.

KUZNETSOV: Thank you so much. Yeah, this was really a pleasure to be here and I'm excited to share some of our story and, you know, it's just the beginning of the story. It continues, you know, we obviously are continuing to take on new problems and continue to grow the team, so I'd love to hear from folks if they're interested to team up.

OLIVER: Of course and we'll put a link to your company website in our show notes, so people can find you easily. Thank you.

KUZNETSOV: Great, thanks so much.

[UPBEAT MUSIC] 

OLIVER: Now it's time for a segment we call Your Turn because it's a chance for our listeners to send in a recommendation that they would like to share. If you're listening, then you're invited to take your turn. Send us a tip for a book, a video, a podcast, or a talk that you found inspirational or amusing or interesting. You can send those to us at NCIICC@NIH.gov. Record a voice memo and send it along. We may just play it on an upcoming episode. Now, I'd like to invite our guests to take their turn. Let's start with our guests from Nucleate, Sonia.

SONIA MARYAM SETAYESH: Awesome. Thank you so much for the opportunity. So, I would love to recommend the book The Power Law: Venture Capital and the Making of a New Future, by Sebastian Mallaby. It is definitely an incredible read. It really will be worth your time, and it really highlights how the Silicon Valley came to be as a marker of innovation in the US.

OLIVER: Sounds like an inspirational story. Of course, we'll put links in the show notes, Geraldine.

GERALDINE EZEKA: Oh Sonia, I'm so glad that you did something educational because now I feel less bad about doing anime. So preface, I'm a super anime nerd, and we were just talking about this anime last week at one of our company's Happy Hours. So there's this anime called Cells at Work. There's two main protagonists, a red cell blood cell and a white blood cell. And it's a really cute kind of humanized version of cells that were kind of going through a bunch of different ordeals. It's kind of like Osmosis Jones but a little bit more anatomically and cellularly correct. So, it's really fun, a really fun show if you're into immunology.

OLIVER: And can you see this on YouTube or where?

GERALDINE EZEKA: I think you can actually watch it on Netflix.

OLIVER: Oh, okay, Netflix.

GERALDINE EZEKA: If you don't have Netflix, you can also watch it at Crunchy Roll. That's where a bunch of anime shows are on.

OLIVER: Okay. We'll try to dig out those links if we can. We'll be emailing you, Geraldine.

GERALDINE EZEKA: Awesome.

OLIVER: Alex.

ALEX KIM: All right. That sounds great. I think I'm going to defer there. I think we have some great recommendations.

OLIVER: All right.

---

OLIVER:  Dr Kuznetsov, go ahead your recommendation, please.

GLEB KUZNETSOV: Oh great. So, one of my most influential books for me, personally, has been a book called Creativity Inc, and it's written by Ed Catmull. And why I love this book so much is it's been something that's been so important to me throughout my career. It's so important to us here at Manifold is the importance of team and culture and doing really hard things. So the story of this book, Creativity Inc, it's about Pixar. It's about the -- you know, the very transformational company that originally created Toy Story and then sort of started a whole field of these kind of next generation of animated stories. And what's really interesting is the challenge they faced is they started with a really strong technical team, really next-generation high-performance compute, could generate these really powerful renderings. But the product was a story, was something of in many ways of a fundamentally different nature. So you have the great technologists and working on cutting-edge technology and you have the product and you have great storytellers that are trying to tell an amazing story, and you need to combine those two types of folks and get them to work quite well together. And so, what Creativity Inc talks about is, how do you build that culture? How do you motivate folks to, you know, both harness creativity but also drive it towards something that ultimately has a very finite end. So for me personally, as CEO of Manifold Bio, you know, we are trying to do something analogous. We use cutting-edge technology to invent new ways of engineering biology, and our product is ultimately a drug. It's something that's going to impact and save the lives of patients. So there's slightly different ways of thinking, and it's important to both harness creativity and innovation. But ultimately, keep it focused towards solving that core problem of creating that drug or creating it. That's something that's going to work, be safe, and ultimately something we can, we can give to a patient.

OLIVER: Great. Thank you. That's a fantastic recommendation. Really appreciate it, and I'd like to make a recommendation as well. This is something lighthearted. "Ten Funny Science Songs that you Need to Hear." They're gathered on one page by Hello Bio, a newsletter. My favorite is actually the first one on that list, "Post-Doc Me Now." I can't sing. So I won't but be careful, one viewing and you might be humming it to yourself for the next few days, and we'll, as always, put a link in the show notes.

[UPBEAT MUSIC] 

 

That’s all we have time for on today’s episode of Inside Cancer Careers! Thank you for joining us and thank you to our guests.  

We want to hear from you – your stories, your ideas and your feedback are always welcome. And you are invited to take your turn to make a recommendation we can share with our listeners. You can reach us at NCIICC@nih.gov.  

Inside Cancer Careers is a collaboration between NCI’s Office of Communications and Public Liaison and the Center for Cancer Training.  

It is produced by Angela Jones and Astrid Masfar and Edited by Janette Goeser. 

A special thanks to Lakshmi Grama and Sabrina Islam-Rahman. 

Join us every first and third Thursday of the month when new episodes can be found wherever you listen – subscribe so you won’t miss an episode. I'm your host Oliver Bogler from the National Cancer Institute and I look forward to sharing your stories here on Inside Cancer Careers.  

If you have questions about cancer or comments about this podcast, email us at NCIinfo@nih.gov or call us at 800-422-6237. And please be sure to mention Inside Cancer Careers in your query. 

We are a production of the U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Thanks for listening.