Persephone CEO Stephanie Culler discusses the potential of understanding gut microbes for truly equitable precision medicine.
When you look up at the night sky, it can be mind-boggling to think of all the distant stars that occupy the visible universe. If we could look within ourselves, we would see another universe inside our digestive system filled with trillions of single-celled aliens that possibly outnumber our own cells.
This unique underworld—the gut microbiome—has been the subject of intense research into their role in human health and disease as well as attracting interest as a potential Trojan horse for personalized medicine.
Persephone Biosciences, aptly named after the Greek goddess of vegetation and queen of the underworld, is poised to unlock the potential of the gut microbiome to improve patient treatment responses. The San Diego company’s goal is to develop personalized medicine by the implementation of population-scale clinical trials, advanced genomics and immunology techniques, and machine learning to decrease global mortality and suffering.
To wield the potential of the gut microbiome for the development of precision medicine for large numbers of patients, Persephone is conducting one of the largest clinical study programs ever pursued in the gut microbiome space. Persephone is collaborating with leading community and academic medical centers to conduct studies enrolling thousands of people to develop precision medicines. That includes the indelible research program “Poop for the Cure,” where Persephone’s team of scientists study donated stool samples to learn more about the gut and develop ways to fight cancer better.
GEN Edge sat down with Stephanie Culler, PhD, CEO and co-founder of Persephone Biosciences, to discuss the challenges of sampling and studying the microbiome at the population level and what they are doing to overcome them.
GEN Edge: What was the impetus for founding Persephone Biosciences?
CULLER: Both myself and my co-founder Steve Van Dien are chemical engineers, and we were fascinated by the role of the microbiome in human health and the fact that virtually every disease that we know of is impacted by the gut in some way. The gut is the largest immune organ, which is much forgotten. Not only does the gut microbiome impact disease, but it also affects how well drugs work, both in terms of efficacy and toxicity.
We founded the company three years ago with the mindset of development and technology platform that we’ve since built. It brings together real-world patient data, where we analyze thousands of stool samples, reflecting the gut microbiome. We extensively profile the immune system using multi-omics techniques. We not only sequenced the gut, but we want to understand the microbial functions important for immune responses to drugs.
We believe in developing equitable precision medicine—we want precision medicine to work for everybody. What we have seen in our own data set as well as published data sets is that patient populations aren’t accurately represented. We know, for many diseases like cancer, that racial and ethnic minorities have significant death rates or are most impacted by some of these diseases. Yet they represent a small fraction of publicly available data sets.
One of the big missions of the company is precision medicine that truly works for all. With the ARGONAUT study that we launched recently, the goal is to extensively profile the cancer microbiome and how it impacts treatment response in a variety of cancers but also amongst ethnic and racial groups. Since they have high death rates for many of those cancers, we want them to be incorporated in these data sets to be sure that the therapies we develop will work for them.
GEN Edge: How does Persephone Biosciences run these population-scale projects, including several clinical trials?
CULLER: We have multiple sites across the country recruiting patients for us, but what we have found is flexibility in decentralized trials. We’re working with CROs that have sites across the United States that are responsible for helping recruit our patients. Everything we need can be done at home. They get to produce their sample at their convenience and call FedEx when it’s ready. It then gets shipped overnight to us. For blood, we have a mobile phlebotomist that comes to their house at their convenience.
We find that the best method for doing our studies is at the patient’s home and by taking this decentralized approach. That flexibility is paramount. This is especially true in the era of COVID-19 where we recognize that the populations that we’re most interested in studying are those that are severely immunocompromised and at risk for COVID-19.
By using a decentralized approach, we can take control of how we access electronic health records as well with an easy consent process. There are many companies where, once a patient consents, we can easily access the full electronic health record and the data that we need for our machine learning models. That becomes a very streamlined, straightforward process and makes the challenge really on us to recruit patients.
GEN Edge: What directions are you trying to grow into as a company?
CULLER: We see this technology platform for oncology as the first frontier for us. We’ve already applied our technology to COVID-19, where we’re developing a novel microbiome medicine to enhance the efficacy of COVID-19 vaccines as well as other respiratory viral vaccines.
We see this platform being able to develop medicines, not just for the microbiome, but for traditional modalities as well for virtually any disease. We want it to work for not just everybody, but for every cancer. We are envisioning a microbiome therapeutic that can work for many indications. That’s really our driving goal—that in any space, doing this population-scale approach, we can develop medicines that can work broadly and for multiple indications or multiple disease stages. For example, we have eyes set on working in neurodegenerative disease, where the microbiome has been shown to have a profound impact on Parkinson’s and Alzheimer’s disease.
In terms of the future trajectory, we want to go public given the amount of capital raises that are needed for these other programs. Oncology was a proof of concept, and now we’re raising significant funds to enable us to get into the clinic with our therapies. But for these other programs, we’re going to need a lot more capital. The work that we do and the way our drug development platform works could be palatable to the public markets. Maybe in the next three to four years, we could be on the trajectory of going public!
GEN Edge: How do you choose which areas of research to move into?
CULLER: Oncology is a passion-driven mission for me. Losing my grandmothers to cancer was the ultimate inspiration for me to become a scientist and dedicate myself as well as many of our team members. It also makes sense from a market standpoint and the impact that the microbiome can have because the links have been pretty clear in terms of the drugs that we work on specifically like checkpoint inhibitors.
In these other spaces, we’ve been approached by potential partners for other disease indications. Why so much of our research is basic is because we’re trying to demonstrate and establish a foundation for our science, but also a mechanism for some of these other diseases. The mechanisms are not really well elucidated. That is a technical risk that we as a small company take on. That has to be weighed when considering moving into these other spaces.
GEN Edge: What is the story behind “Poop for the Cure,” and how has the public reacted to it?
CULLER: It’s been incredible! To preface, one thing that I did not recognize when we started in this space is the stigma associated with giving a stool sample. It’s difficult and an industry-wide barrier to the microbiome space and our research because we do such extensive analysis. While children may be excited about pooping, adults aren’t, especially those that are severely ill.
Several things led to “Poop for the Cure.” We did some pilot studies with currently available commercial kits to collect stool samples. What happened was, we had a clinical collaboration and we were using these kits to understand the user experience but also to establish our technology. Cancer patients were refusing to get stool samples because of the stigma but also the kit we were using was difficult to use. Many of them are physically challenged and said, “I’m not going to participate in your study. I’d rather get poked by a needle to give you blood, which I’m doing, but I’m not going to give you stool.”
At that point, our research basically stopped, and we had to go back to the drawing board. I thought that we have to empower people and make this easier. We have to take into account this user feedback. We came up with “Poop for the Cure,” which is really a call to action campaign for anybody with cancer or in remission and loved ones who have cancer, to educate them about why microbiome and stool analysis is so important. Not just for colorectal cancer, as many people think, but for all cancers and, furthermore, all disease.
The kit itself is really a game-changer. We designed it to look like a luxury handbag. The kit is easy to use: no mess, minimal handling. It has an easy to use stool bracketing container that can go on any toilet, especially those that might be in the hospital setting and take all the concerns from the patient out of the way. To ship it back to us, all they have to do is call FedEx, and FedEx comes to the door and picks it up. In return, we give the patients the t-shirt that says “Poop for the Cure,” a $50 gift card, and also some thank you notes.
This has been wildly successful. We interact a lot with the donors from “Poop for the Cure” because it is a citizen scientist type effort. It is IRB approved, but it allows us to have access and communicate with donors. Once we launched our ARGONAUT study, over 50 donors with cancer said that they wanted to support our research and emailed me asking how they can help us. It is incredibly touching to hear these cancer patients who are struggling and fighting so hard, and they are huge advocates for research and science. For us, the learnings have been that these grassroots efforts do work.
That’s how we have continued to campaign and educate the public on the importance of stool donation and analysis. We hope that what comes out of our research not only helps us develop therapies that can help cancer prevent cancer in the long run. We’re thinking about that diagnosing cancer as well, but also to be part of everybody’s physical exams or part of your health communication with your physician to date. I can tell so much about a person’s health and potential diseases they may get from a stool sample. That technology is just not available to the masses.
GEN Edge: Have you thought about creating an at-home testing kit for the microbiome?
CULLER: In the future, we would like to be more potentially consumer-facing or have a product that is clinically approved so that it can be in the context of working with a physician. We want to be able to make this technology accessible to the masses.
GEN Edge: What do Persephone Bioscience’s 1-, 5-, and 10-year plans look like?
CULLER: In the immediate 1–2 years, it’s developing the largest clinical gut immune database that exists to be able to rapidly develop oncology therapeutics. In the next five years, I can see that database expanding ten to a hundredfold where we can then apply it to many diseases. In a decade, we’ll have multiple therapeutic approvals for many indications as well as applications of our technology for the broad masses.
We founded the company with the mission of precision medicine. We want to develop a new drug development paradigm. We believe that it’s going to develop groundbreaking medicines, but it’s how we develop our medicines and design our therapeutics based on patient data that is truly unique. Most people don’t understand that biospecimen collection is very challenging. When you combine it with severely ill people it’s even more difficult. We’ve developed an infrastructure nationwide and a way to communicate with the patients and work with them on gathering this data.
What I want people to take from what we do is that passion for patients. Taking this patient-centric approach to do drug discovery, they need to be included in the conversation early on. Data from diverse populations need to be there. You shouldn’t have to wait till after a drug is approved before you test it in a diverse patient population. You should know the data right upfront. We believe in profiling patients first, prior to the drug discovery drug development portion. We’ll be having drug targets in hand that are important for human disease and for a diverse population.