What’s going on in that gastrointestinal tract of yours? Well, we have a general idea, but there is mounting evidence that the gut and the microbes that live there play an important role in a wide variety of health problems. Persephone is a biotech startup that — with the help of $15 million and a lot of poop – builds a library of the human microbiome and compiles a best-of list of beneficial life forms that can do everything from ease digestion to fight serious disease.
The democratization of once exclusive and expensive tools such as rapid genetic sequencing has nurtured a new generation of biotech companies and therapeutic approaches. This case takes a closer look at how everyone’s microbiome – the often unique set of microorganisms that live in and on our bodies and perform different tasks for mutual benefit – differs and what those differences mean for our health.
Co-founder Stephanie Culler came from a background of genetics work at Geomatica, where they worked to produce chemicals normally extracted from petroleum by modifying bacteria to make it through fermentation.
“It took 5 years of genetic engineering, but it worked — it allowed us to build a blueprint of how to manipulate a bacterium,” she said. “Now we are doing something similar with the same tools. But we used to map a single microbe, and now we’re doing that with multiple microbes, and we’re building an accurate map of the entire gut biome.”
There is a lack of fundamental understanding in this area, she explained. Despite the evidence that it is involved in many processes, there is historically insufficient data to answer questions such as how the microbiome influences disease progression, the effectiveness of therapies, the development of the immune system, even things like allergies. Part of the reason is the difficulty of collecting enough raw research material.
The company has trained machine learning models on large datasets it has compiled itself by painstakingly collecting stool samples from a large number of people, both healthy and suffering from various conditions.
“It’s not easy to give poop samples — there’s a stigma,” Culler explained. “So we focused on how we can easily make it happen. The initial funds we received through Y Combinator [one of our favorites in 2018] set us up to develop that infrastructure, to get large amounts of patient data.”
The microbes in the samples were isolated, sequenced, and cataloged, then that data was combined with a host of other health records — blood tests, behavior, medications, and so on. Machine learning is an efficient way to sift through those kinds of noisy data sets, and it identified both patterns worth investigating and what Culler called “superheroes” among the microbes.
For example, in the years preceding the diagnosis of colon cancer, a certain strain or functional type of bacteria in the intestine may become extinct. Why? No one knows but not you to have to know for that kind of early marker to save lives. And what if his presence could be restored? This could very well have a positive therapeutic or preventive effect.
“You and I may have different strains of the same bacteria, but there’s a consensus about good functions you want,” Culler said. “But in disease studies, they may be completely missing, or they have other, scary strains.”
“As we get older, our diet changes, we get sick, we take antibiotics…and the microbiome starts to disappear,” she continued. “We’re trying to collect all the right microbes: a one size fits all, trained on our data, consensus set of organisms that everyone needs — one super pill that is a new category of probiotic.”
It’s a little more complicated than that, though, Culler explained. Different age groups and circumstances would likely have different needs, although a set of superheroes would probably be helpful (and certainly not harmful) to everyone.
You may be wondering how these differ from the probiotic pills and potions out there already. Well, those may be helpful to some, but the truth is, they’re not really our local microfauna.
“A lot of what we have on the market are ancient strains that were discovered over 100 years ago, a lot of it from milk-based products – these are not true members of the gut microbiome. We analyzed 150 products and there were only 29 strains that overlapped.” having a healthy microbiome,” Culler said. (And no superheroes.)
Compare that to the thousands of candidates they’ve identified, all of which come directly from humans, and recently, so they reflect, among other things, a modern diet. Instead of a critter someone found in milk a century ago, you could have the best of the breed from real people.
There are two major avenues for Persephone, both of which the company hopes to realize in the coming year. The easier of the two is the probiotic supplement, which just needs to be tested and is “generally recognized as safe” by the FDA. This is the same designation that every other supplement is given that suggests general health benefits, but no therapeutic claims, such as that it cures something.
These supplements would be primarily intended for pediatric use as more and more babies are born with incomplete gut microbiomes due to things like c-sections, antibiotics and formula feeding. As helpful as those things are, they seem to work to the detriment of the gut — possibly contributing to the massive increase in allergies, among other things. A shelf-stable liquid probiotic additive could be a standard addition to any new parent’s baby bag.
More testing of the infant gut biome is needed, and Persephone will announce a major new partnership in infant health and a new nationwide study to be launched very soon. Fortunately, “collecting baby poop is super easy,” Culler said. If anything parents have too many monsters.
The company would scale to older ages and adults over time, while investigating specific applications such as alleviating IBS, inflammation and other problems these microbes can cause.
The other way forward, which Persephone is pursuing at the same time, is therapeutically applying microbes to cancer treatment, which is believed to enhance the effect of immunotherapy drugs. This is the kind of thing that needs more serious FDA approval through clinical trials.
“We want to be in the clinic in a year and a half; We will definitely be there in 2024 for lung cancer,” Culler said, referring to part of a collaboration with Johnson & Johnson. “Besides oncology, we are very interested in the gut-brain axis; these superbugs [i.e. the superhero microbes, not viruses] are important for any disease.”
There is also a new collaboration with Ginkgo Bioworks on new synthetic biotechnology and ARGONAUT, a large-scale study of the gut-immune axis looking for biomarkers for the detection and treatment of cancer. There’s plenty on the company’s board, so don’t be surprised if you see Persephone-powered studies popping up with some regularity.
The advancement attracted this $15 million seed round co-led by First Bight Ventures and Propel Bio Partners, with participation from Y Combinator, Fifty Years, Susa Ventures, American Cancer Society’s BrightEdge Fund, Pioneer Fund and ZhenFund.