The loss of two grandmothers to cancer propelled the daughter of an entrepreneurial family, Stephanie Culler, to a Ph.D. at Caltech and eventually to founding Persephone Microbiome. The VC-funded startup seeks to use gut bacteria to increase the success of cancer therapies. Persephone is also launching a probiotic for infants. Fascinating chat with a brilliant and articulate scientific founder.
Highlights:
Sal Daher Introduces Stephanie Culler, Ph.D. Co-Founder of Persephone Microbiome
Persephone’s Business Model Is to Partner with Big Pharma to Develop Products Based on Its Platform
A Probiotic for Babies and Infants Is Coming in Early 2024
Results from the Largest Study in the US of Infant Gut Microbiome Were Unsettling
Causes of Insufficiencies in the Gut Biome of Babies
“Upwards of 80% of cells of our immune system is in our gut.”
“...if you have a good microbiome, you're much more likely to respond to treatment.”
“We are wet lab and in silico.”
How Persephone Got Funded
The Importance of Enrolling Populations Previously Under-represented in Studies
The Promise of Population-Scale Data Sets
Scanning Large Patient Populations Unencumbered by Animal Studies
Why You Should Help This Podcast Get Found
Stephanie Culler, Ph.D.’s Entrepreneurial Journey
Entrepreneurial Family that Lost Two Grandmothers to Cancer
Sal’s Appreciation of Articulate Chemical Engineers Like Stephanie
Stephanie’s Experience at Y Combinator
How Stephanie Culler Connected with Leen Kawas
Stephanie’s Parting Thoughts on Biotech Winter
ANGEL INVEST BOSTON IS SPONSORED BY:
Transcript of “Cancer & the Gut Biome”
GUEST: Stephanie Culler, ph.D.
Sal Daher: I'm really proud to say that the Angel Invest Boston podcast is sponsored by Purdue University Entrepreneurship and Peter Fasse, patent attorney at Fish & Richardson.
Purdue is exceptional in its support of its faculty of its top five engineering school in helping them get their technology from the lab out to the market, out to industry, out to the clinic.
Peter Fasse is also a great sport to entrepreneurs. He is a patent attorney specializing in microfluidics and has been tremendously helpful to some of the startups which I'm involved, including a startup, came out of Purdue, Savran Technologies.
I'm proud to have these two sponsors for my podcast.
Sal Daher Introduces Stephanie Culler, Ph.D. Co-Founder of Persephone Microbiome
Welcome to Angel Invest Boston, conversations with Boston's most interesting founders and angels today. We're very privileged to have a biotech founder who is in San Diego, California. Her name is Stephanie Culler, PhD. Hi, Stephanie.
Stephanie Culler: Hi, Sal.
Sal Daher: Great. Stephanie was connected to me by Leen Kawas. Thank you, Leen, who has backed the company, Persephone Microbiome started by Stephanie Culler. I got very interested. The idea of babies having microbiomes and being important, it makes sense to me now, but that idea never occurred to me before. This is what her company does, one of the things that she's focusing on. Stephanie Culler, what problem is Persephone Microbiome solving?
Stephanie Culler: We're really focused on solving the problem of damaged microbiomes, which have an impact on causing disease, how somebody may respond to treatment to disease, specifically in cancer, which has been our focus, but a number of diseases. As well as how it can impact us before we're even born. Persephone focuses on performing real-world studies where we collect stool samples that allows us to map the microbiome of people to understand what's wrong or missing about their microbiomes.
From that, using machine learning, we're able to detect what kinds of bacteria and their functions or properties are needed for health, are needed to respond to the latest immunotherapy drug, are needed to prevent food allergies, or eczema, or other diseases that can potentially impact newborns, for example. Those are the kinds of things that we're doing at Persephone, and the kinds of problems that we're looking to solve.
Sal Daher: What is your business model?
Persephone’s Business Model Is to Partner with Big Pharma to Develop Products Based on Its Platform
Stephanie Culler: Right now, we're really B2B focused. We partner with pharma companies. We partner with consumer companies on doing two types of product development and analyses. One, as I mentioned, we have a technology platform where we're really trying to understand what's wrong or damaged about the microbiome. That has led us to developing a platform that can discover new biomarkers that pharma is interested in understanding how they can make therapeutics off of but also for us at Persephone, as we're developing therapeutics in our own right, namely in oncology, but potentially other indications moving forward.
The second area is that we partner in product development. Long term, we want to partner in co-development of therapeutics, but in the near term we're looking at partnerships to develop consumer probiotics in the infant health space.
Sal Daher: How far along is that effort, the consumer effort?
A Probiotic for Babies and Infants Is Coming in Early 2024
Stephanie Culler: We are actually going to hopefully have a product commercialized and be ready for infants early next year, so we're knee-deep in development as we speak.
Sal Daher: Is the use of that going to be under prescription? Is that just an over-the-counter product?
Stephanie Culler: It's going to be over-the-counter, over-the-counter product considered to be a supplement. We're looking at impacting not just newborns but more importantly, the first three years of life.
Sal Daher: Is this something for which you're going to be testing the babies to see if they're deficient in any way or is this just something generally healthy?
Results from the Largest Study in the US of Infant Gut Microbiome Were Unsettling
Stephanie Culler: Towards that, we conducted a very large study last year called My Baby Biome. This was the largest study ever to be done in the US to map the infant gut microbiome in a high-resolution manner. That's where we've discovered that more than 50% of babies in the US have damaged microbiomes. Of the other 50%, they're not doing that great. They could definitely improve their microbiome. They're just missing key microbes.
Part of our product offering right now is just developing the product that they need, what's missing from their microbiomes. We may eventually develop a commercial test off of our learnings, but that's something that is much more longer-term looking.
Sal Daher: I guess it's simple enough to just have a few of these microorganisms in a probiotic that is-- If you already have the full expression of the flora in your gut, it's not going to harm you-
Stephanie Culler: Exactly.
Sal Daher: -but if you're missing something, then it could be helpful. What leads to having this absence of the necessary microorganisms?
Causes of Insufficiencies in the Gut Biome of Babies
Stephanie Culler: It's a multi-generational issue. It's the fact that babies today are being born via C-section. It's the prevalence of antibiotic use that is killing off those microbes. It's poor maternal diet and it's formula use. The thing here is that babies inherit their microbes from mother, but if mother doesn't have those microbes, if mother has bad microbes, that's what they're going to get. That's what we think is the biggest issue here in addition to obviously C-sections. C-section babies are not born with those microbes.
Sal Daher: Right. You've also mentioned that if they're not being breastfed also, it deprives them of the chance of having transmission of the microorganisms from the mother.
Stephanie Culler: Yes. There's a certain component, maybe let's say upwards of 30% of the-- There's actual microbes in breast milk that help colonize the microbiome. More importantly, there are special sugars in mother's milk. It's called human milk oligosaccharides that specifically feed gut microbes. That's what the babies need. That's why there's actually infant-type microbes because those are the microbes that respond well to mothers' milk.
Sal Daher: A particular type of oligosaccharides?
Stephanie Culler: Yes, exactly.
Sal Daher: It's present in mother's milk. I didn't know that. Both my daughters, they were breastfed. I remember my wife making very particular efforts. Actually, I have a good friend who was from San Diego. She was a member of La Leche League. She was just very big on breastfeeding. [laughs] Shout out to her.
Stephanie Culler: There's so many benefits beyond that microbiome component, which is important for the immune system, but it is really on the health of the baby. The longer that the babies are breast fed, the lower risk they have for developing diseases.
Sal Daher: That's tremendous. How did you stumble on this?
How the Focus on the Microbiome of Babies Came About
Stephanie Culler: Historically at Persephone, we've been focused in oncology, a personal passion of mine, but also an area that we think that the microbiome can have one of the most greatest impacts. As we were pursuing our oncology work, a big pharma company actually approached us and said, "You should really think about solving the infant microbiome problem." I knew that there was an issue because I've heard talks at conferences about it. It was also at a time when I had a six-month-year-old baby girl. [laughs] Everything is “baby” at that point. Baby is just on my brain.
Sal Daher: Baby AI, baby-- It's just like--
Stephanie Culler: We took a look at it and we said, "You know what? Let's do a pilot study. Let's quickly look at the microbiome of every infant we know right now." The results were alarming. We found out that most of the babies had damaged microbiomes. What was even more concerning, that really got me upset, was the fact that many of these babies had the same types of bacteria that we see in advanced-age cancer patients, potentially pathogens, infectious organisms, those that are highly inflammatory.
There's no reason that a two-month-old baby should have those types of microbes instead of-- It was at that point that we said, "You know what? We're going all in. We're going to solve this problem."
Sal Daher: Wow. That is fascinating. Some really mind-opening things. I am an investor in a company called Delfina. Have you ever run across them?
Stephanie Culler: Yes, just on LinkedIn.
Sal Daher: Through that, I became aware of the fact that just how troublesome so many pregnancies are because of the health of the mother, and that there are things you can do to alleviate that. Senan Ebrahim and his co-founders are doing really wonderful work. It's basically assembling data. It's all about creating data. They're not discovering a new molecule or anything like that. It's all looking at existing data and putting it in a format that is accessible. His brother who's very much a software guy and Senan is a MD PhD from Harvard. He just went straight into starting a company because this is so compelling.
They're beginning to prove out. They don't have enough patients yet, but they have early indications that this app that they have providing information, improves outcomes for these mothers. Perhaps they will also watch their health enough so that they can have a good gut microbiome. Right now, the big thing is watching their blood sugar or watching their blood pressure, keeping track of that. This is very fascinating.
How did you get on to the microbiome connection with cancer?
Stephanie Culler: When we started the company about a little over 5 years ago, there was talk and there was scientific literature in mice only, not in patients yet. This is in 2017 around that the microbiome was associated with the response to checkpoint inhibitors, these groundbreaking amino therapy drugs that can be cures for some patients, especially they found with advanced stage melanoma cancer patients.
Sal Daher: Would you unpack checkpoint inhibitors for people who are not specialists in the area?
Stephanie Culler: Yes.
Sal Daher: ...how the checkpoint inhibitors work.
Stephanie Culler: Checkpoint inhibitors are a type of drug that essentially release the breaks off of the immune system and allow it to recognize and attack and kill cancer cells very effectively. A released-the-brake mechanism, essentially. These are powerful drugs. They have cured individuals. The challenge with them--
Sal Daher: I just want to complete the thought. What they're doing is they're getting around the defense mechanisms of the cancer because the cancer has mechanisms for shutting off our immune system.
Stephanie Culler: Exactly. It puts a blindfold. It essentially rips the blindfold off of the immune system and allows it to actually see the cancer.
Sal Daher: A cancer cell. It's a little bit like Winnie the Pooh. You know I'm a-- What is it? "I'm a raincloud. I'm a raincloud." The body's fooled by that, and so the checkpoint inhibitor says, "Ah, that signal that I'm getting not to attack the cell, it's a lie. I'm going to attack it."
Stephanie Culler: Exactly. The challenge here is while these are amazing therapeutics, they don't work for a lot of patients. Perhaps maybe upwards of 70% of patients are not responding to these curative drugs. Pharma has focused a lot recently on trying to make them work better through combinations with other therapeutics. Along the way, it was discovered that the microbiome is actually playing a huge role in how well they work, but nobody really knows how the microbiome is doing that.
“Upwards of 80% of cells of our immune system is in our gut.”
Likely, it's obviously through the immune system. One thing that I didn't have an appreciation for until I started the company was how much of our immune system is in our gut. Upwards of 80% of cells of our immune system is in our gut. The kinds of bacteria that we have, what they produce is in constant communication with our immune system. That's what's happening here. If you have a bad microbiome, you are much more likely to not respond to these groundbreaking drugs.
If you have a healthy microbiome, you're much more likely to respond. That was found out a few years after this initial finding in mice that indeed it's the case in patients, that if you have a good microbiome, you're much more likely to respond to treatment. What we have done to try to understand this better is do some large studies where we map the cancer gut microbiome to better understand what's wrong, what's missing in the case of cancer patients who are non-responders to treatment and using machine learning tools, determine what are the right bacteria functions? What do we need to repair in those patients?
“...if you have a good microbiome, you're much more likely to respond to treatment.”
Sal Daher: One note for the listeners. Machine learning just means algorithms that are really good at figuring things out with unstructured data. Just feed it a lot of data. You program it with data.
Stephanie Culler: Yes. Program with lots of data.
Sal Daher: With lots of data. It's these patterns that we human beings can't see. Then it might say, "Ah, there's a pattern here that these types of cancers, when we have these microorganisms in this state, something's happening here."
You mentioned that you're a technology platform. It is the software that you have put together, the algorithms that you put together for looking at this. It's not a wet lab technology. It is strictly in silico, or is it—
“We are wet lab and in silico.”
Stephanie Culler: We are wet lab and in silico.
Sal Daher: And in silico, okay.
Stephanie Culler: What we do is we use the really in silico to understand--
Sal Daher: I'm sorry in silico means in a computer in the silicon chip.
Stephanie Culler: Yes.
Sal Daher: Test tubes also have silicon in them [sotto voce]. It gets confusing. [laughter] The sand, you know. Okay. The making of glass.
Stephanie Culler: Not inside the laboratory. In the cloud computing laboratory-
Sal Daher: Exactly.
Stephanie Culler: -we determine what is wrong about the microbiome of these patients. Then that's where we go to the wet lab. We go to the wet lab to isolate different microbes from the stool samples we collect, namely from healthy individuals. It's these microbes that we genetically engineer with synthetic biology tools, so just recombinant DNA engineering. We engineer these microbes to produce different metabolites or chemicals that are what's essentially missing or dysregulated. We're repairing those functions, but we use genetic engineering for a variety of reasons. Is that we want that particular bacteria to work the same across an entire population of patients. These are living organisms. They may not behave equally if they're not programmed to do so.
How Persephone Got Funded
Sal Daher: Right. Excellent, excellent. The backing that you've had for Persephone has come from what sources?
Stephanie Culler: Angels but also, VC. We were Y Combinator in winter batch 2018.
Sal Daher: Hotdog. Amazing.
Stephanie Culler: More recently, a Series Seed led by Leen Kawas and Propel Bio.
Sal Daher: Go, Propel Bio.
Stephanie Culler: Yes, Propel Bio and First Bight Ventures, the synthetic biology-focused fund. We've closed $15 million to date.
Sal Daher: Congratulations.
Stephanie Culler: Thank you.
Sal Daher: Very interesting. Is there anything else that you want to touch on with regards to Persephone Microbiome?
The Importance of Enrolling Populations Previously Under-represented in Studies
Stephanie Culler: Definitely a focus on health equity. When we're doing our observational studies, we're really focused on making sure that the samples that we get really reflect the entire population. We make sure that there's representation from ethnic and racial minorities. In some cases, above what they are in our general population, especially if they have a higher incidence of a particular disease like colorectal cancer.
Sal Daher: Exactly. The case of Delfina, initial studies were in reservations where there were some particularly bad outcomes. It's the places where you can help the most. Those are the populations where you have the most chance, so you need to go where the people being afflicted are.
Stephanie Culler: Exactly, yes.
Sal Daher: Yes. It's good that you're doing that because [chuckles] in the past, as we know, we tended to make assumptions about populations that weren't always born out in the real world.
Stephanie Culler: Yes. Especially, the microbiome is influenced by these different factors. It's influenced by what we eat, where we live.
The Promise of Population-Scale Data Sets
Sal Daher: Yes. I suspect that what's going to go on in the future with the kind of computing approach to the life sciences is that we're going to be able to learn because we'll be seeing such larger data sets than your 300-400 person randomized controlled trial has in it, that you're going to be able to zero-in on problems of subpopulation. You can't do it with a 400-patient sample, but if you have 4 million patients and if you have data from 4 million people, then all these things become possible.
You could drill down to very, very specific populations, so people who live on the north side of this place and so on, they have this response and so forth. I'm very excited about this prospect of data. I'm an investor in a company called Healthjump. The founder, Martin Aboitiz, is my brother-in-law. I find it just fascinating. That's one of the reasons why I'm very involved in digital health is because of Martin and my investment in the company. In the middle of COVID, they contributed 80 million deidentified patient records in a data lake to the COVID research database.
This was the basis of, for example, The Economist wrote a very interesting feature article on all the things about COVID. They were able to discover that you couldn't tell from the existing information that you have. When you have 80 million, enough data you're getting everything is updated, and so forth, you can see so much stuff in there. We're going to be learning really tremendous stuff, really be able to figure out exactly why some checkpoint inhibitor isn't working in this person that lives somewhere, that eats this, and that has this kind of profile.
Stephanie Culler: Absolutely.
Sal Daher: That is awesome. That is really, really exciting. If there's anything else you want to say about the company and the founding of the company, what the company's doing, perhaps, I could cover it now. My thought was to do a brief promo for the podcast and then go into your personal journey to becoming an entrepreneur.
Stephanie Culler: Maybe, a little bit about the technology.
Sal Daher: Oh, please.
Microbiome Avatar Allows Rapid Prototyping
Stephanie Culler: Yes. One of the things that I'm really excited about that we've been working on at Persephone, I call it the Microbiome Avatar. When we are doing our observational studies, we collect stool samples to map and understand the microbiome, but we can use those samples on a chip to mimic the environment of the human gut. We could be able to screen thousands of different therapeutics, consumer products in the background of human microbiomes. It allows us to rapidly prototype.
For us, that's been a little bit of the holy grail because it unlocks the ability to have a drug discovery funnel. That's always been the question in microbiome is how do you screen for efficacy? Well, we can do that because we have microbiomes, and microbiome samples, and we can do it in high throughput with automation.
Sal Daher: Excellent. You're automating the process of categorizing the microbiome of individuals.
Stephanie Culler: Exactly, yes. We can evaluate our therapeutics in the context of the patients we would probably treat. It gives us a realistic setup. Then as we get into the clinic and do clinical trials, we can then use machine learning to see, hey, was our in-vitro platform predictive of the clinical trial result, where we were accurately predicting the impact of our intervention, our therapeutic on the microbiome.
Sal Daher: Okay. Basically, you take the sample and then you categorize all the microorganisms and I don't know what other indicia you have other than just the type of microorganism. Then based on that, you try to match that with different outcomes under different circumstances, different therapies, and then you'd get some knowledge out of that.
Scanning Large Patient Populations Unencumbered by Animal Studies
Stephanie Culler: Exactly. It allows us to also scan a really large space of potential patients without having to do animal studies, for example, which are very low throughput and expensive, and have a lot of issues with them because the mouse gut is very different than the human gut, for example.
Sal Daher: It's amazing. Mouse models are very, "Oh, it's good we have them," but they're also very limited.
Stephanie Culler: Exactly.
Sal Daher: Mice with diabetes, for example, you can just do very simple things to them and then they stop being diabetic. Basically, they lose weight and then they're not diabetic anymore, so their insulin resistance doesn't mimic the insulin resistance of human beings.
Stephanie Culler: Exactly.
Sal Daher: Pigs don't get certain kinds of cancers. Anyway, this is tremendous.
Why You Should Help This Podcast Get Found
Let me do a very brief promo for the podcast, which is really an invitation to people who are enjoying this really fascinating exploration of this little-discussed area of human health, the microbiome of babies, and the microbiome's relation to cancer therapy, and what cancer therapies work and don't based on the microbiome.
The way to upvote this type of content and to get it found more easily in the podcast world is to first follow us on whatever podcast app you listen to and also, please do a rating. We love five-star ratings. Please do a written review because it values your rating. It privileges your rating. Written reviews, they don't have to be very long. They don't even have to be particularly positive.
They can be very direct and frank, but the fact that you took time to write something tells the algorithm that it's content that's worth having other people listen and therefore, it'll be shown to more people. We're all playing the game of the algorithm, unfortunately. I've heard somewhere, a podcast, that algorithms are making songs shorter and simpler, pop songs.
Stephanie Culler, Ph.D.’s Entrepreneurial Journey
Stephanie Culler: Yes, makes sense.
Sal Daher: Shrinking the complexity of pop songs, those four-minute songs they'll play, they get shorter and simpler, harmonically and all sorts of ways. We're all dancing the tune of the algorithm.
Anyway, let's get into an exploration now of your entrepreneurial path. You grew up in Orange County, California. You got into science somehow. Smart kid just wanted to do science. Were there scientists in your family?
Stephanie Culler: No scientists. I'm the first. [chuckles] I'm the first to also get a doctorate.
Sal Daher: Okay. You discovered that you like science. That happens a lot. It's somebody who's smart, who's good at learning things, and who's curious. They end up in science, but the idea of starting a company is very unusual. How did that come about?
Entrepreneurial Family that Lost Two Grandmothers to Cancer
Stephanie Culler: Well, I think both go hand in hand. I do come from a long line of entrepreneurs. My mother is an entrepreneur.
Sal Daher: This is very interesting. You come from a family that no PhDs, but they're entrepreneurs.
Stephanie Culler: They're all entrepreneurs in business and various and real estate and other avenues. My mom is actually fashion designer. She had her own company in that area. From the science side, it goes back to why our initial focus at Persephone has been in oncology. I lost both of my grandmothers to cancer when I was a young teenager, within less than a year apart.
Sal Daher: Oh, that is crushing.
Stephanie Culler: That was devastating for the family. I felt really helpless. That was where I decided I wanted to become a scientist to help develop the next-generation therapeutics. What that looked like, I had no idea. [chuckles] That's why I went and got my PhD at Caltech in Pasadena. It was there I worked on gene therapy for oncology applications. At that point, I really got excited about being an entrepreneur, but I recognized I didn't know anything about starting a company. I needed to get some industry experience. That was part of the journey. I came down to San Diego, worked for a company in the industrial biotechnology space where I met my co-founder.
We had success there working with microbes similar what we have in the microbiome but engineering them to make novel products.
Sal’s Appreciation of Articulate Chemical Engineers Like Stephanie
Sal Daher: Expand that. Tell me about your co-founder and what the division of labor is.
Stephanie Culler: Yes. Well, we have a similar pedigree. We're both chemical engineers. He's actually academically related to me.
Sal Daher: Oh, I love chemical engineers. Chemical engineers are so smart. Some of the most impressive founders I've met are chemical engineers who are articulate. Sean Kevlahan, Armon Sharei. These guys are really impressive.
Stephanie Culler: He's also a chemical engineer. He is more behind the scenes, whereas I'm the face in front of the company, but he handles--
Sal Daher: A communicative chemical engineer. Okay.
Stephanie Culler: He handles all the technology development, and handling the data science computational. I'm more on the experimental side. We're very complimentary.
Sal Daher: Are you willing to reveal his name?
Stephanie Culler: Oh, yes. Steve Van Dien.
Sal Daher: Steve Van Dien. V-A-N D-I-E-N.
Stephanie Culler: Correct.
Sal Daher: You met your co-founder, so please go ahead.
Stephanie Culler: Yes, I met my co-founder at this company called Genomatica in San Diego, where we were engineering microbes to produce useful compounds, namely in chemicals, so that we can make them renewably via fermentation and bioprocesses. Under my co-founder's leadership, we commercialized our first product there. It was really after commercial success there that we started thinking, what's next? I wanted to start a company, and he was very interested. We stumbled across the microbiome space. Always been fascinated, but we were like, "Where can our skills and being experts in how bacteria function, microbes--" as well as my personal passion in human health.
We thought microbiome was the best place for our abilities to develop technology platforms. Microbiome impacts almost every disease that we know of, impacts over 50 FDA-approved drugs, how they work, and before we were even born. Nobody's really understanding the mechanism. That was the impetus for starting the company. Given that everybody in my family is an entrepreneur, I didn't really have reservations. I just jumped into it. Yes, it was scary, and took me a while to find investors. I know the best scientists in the world. I know many Nobel laureates, in fact [chuckles], but I don't know investors.
Sal Daher: You said you had angel investors backing you. Which angel groups?
Stephanie Culler: No angel groups. Just individuals and family offices.
Sal Daher: Oh family offices.
Stephanie Culler: Namely a lot of biotech, pharma pioneers, of course, friends and family. Then through Y Combinator, that was really what elevated us.
Stephanie’s Experience at Y Combinator
Sal Daher: Of course, Y Combinator? Yes. Tremendous way to connect with investors. I'm in Cambridge, Massachusetts, and I'm surrounded by life science companies. They really have a hard time getting funding. Tell me a little bit about Y Combinator. What's the experience like at Y Combinator for a life science company?
Stephanie Culler: It's an invaluable experience. I think for me, I'm a technical founder coming from the bench, and then starting a company. I didn't really know how to communicate with investors. You go through the PhD process and it's all about how you communicate your science. It's very, very highly technical, but that's not how you pitch to investors. For me, Y Combinator was so many different aspects. One, it's meeting other founders who are in my shoes. It was other technical, scientific founders who were starting companies in the biotech space, so having that camaraderie, that community. Second, it was also about how to run your startup.
What are the necessary tools as a founder to be successful? How do you pitch investors? What are the things that you need to be doing? How do you continue to raise money for your company? How do you ultimately don't need investor money? Start generating revenue? They were historically more focused in tech, but they've had a huge focus in the last five years, I would say, in biotech, and have made investments to having really good partners that have that expertise. A lot of the learnings that Y Combinators had over how long it's been around, it doesn't matter what industry you in, they still apply. The rules to having a successful startup are important.
Sal Daher: Oh, yes. Paul Graham started Y Combinator here in Cambridge.
Stephanie Culler: That's right. Yes.
Sal Daher: It moved out to the West Coast and it just grew and grew and grew. Now I understand, they have 500 startups in class. It's really-
Stephanie Culler: It's incredible, yes.
Sal Daher: -a major undertaking. Tremendous, tremendous. You come from a family of entrepreneurs. Your two grandmothers were afflicted with cancer and passed away pretty close in time to each other. That spurred you to go in the direction of discovering some kind of a cure improving the chances of their-- I have never heard people going in that direction. You've come from an entrepreneurial background, you go to science, and then you become entrepreneur. That is a first for me.
Stephanie Culler: Yes. [laughs]
How Stephanie Culler Connected with Leen Kawas
Sal Daher: That is truly amazing. [chuckles] How did you connect with Leen?
Stephanie Culler: I met Leen, I think, in 2018. We were both in a course for female CEOs. This was at the time that she was at Athira and midway through their fundraising journey prior to IPO, maybe a year or two before IPO. We were in that course together and we got to know each other there. We hadn't connected until she started the fund and it was actually through one of the connections. It was actually a third party that was associated with that CEO organization that we attended had linked us up. They said, "You really should talk to Leen."
I said, "Oh, I didn't know she had a fund. I didn't know this was what she was doing." I hadn't caught up with her, and we connected. We connected anyways when we were in that course together, but there was just so much in common and I think the kind of things that we were doing at Persephone really resonated with her investor thesis. She really lives up to what they're aspiring to be at Propel. They're trying to get you to propel to the next stage in growth of your company. She really rolls up her sleeves and is very passionate about helping founders that are in her portfolio of founders.
Stephanie’s Parting Thoughts on Biotech Winter
Sal Daher: Interesting. There is right now a very difficult environment for life science companies in public markets. Do you have a perspective on that?
Stephanie Culler: Yes. I mean, for earlier stage, it's not as impacted as some of these later stage financings, but it is still less. There are less financings, more reasonable valuations for investors. It's more difficult to find investors that are deploying active capital or capital actively, but throughout the journey of Persephone, we've always had-- There have been great times of capital was easier to acquire, and there were harder times. It doesn't surprise me.
It just means that we have to really focus on hitting our milestones and inflection points. It's just going to be tougher than usual. That's just the way it's going to be.
Sal Daher: Thank you for the very thoughtful answer on the dearth of funding for biotech and how it's affecting mostly later-stage companies but early-stage companies are also feeling it to a certain extent. This has been a really interesting interview. I'm very grateful to Leen Kawas for introducing us, and I thank you for making the time to be in the Angel Invest Boston podcast.
Stephanie Culler: Thank you for having me.
Sal Daher: Stephanie Culler, PhD, co-founder of Persephone Microbiome focusing on the connection between cancer and the microbiome and also on the deficiencies of gut microbiome organisms in babies and infants. Tremendous, very interesting conversation. This is Angel Invest Boston. I'm Sal Daher. Thanks for listening.
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I'm glad you were able to join us. Our engineer is Raul Rosa. Our theme was composed by John McKusick. Our graphic design is by Katharine Woodman-Maynard. Our host is coached by Grace Daher.