By Catherine Cheney // 19 July 2018
DAVIS, Calif. — The team at Evolve BioSystems, a privately held microbiome company in Davis, California, spends a lot of time talking about a woman named Sloane. She appears in a large cardboard poster in the corner of their offices, surrounded by stats: “85 percent of all babies are born to millennials; 17.4 hours per week on social media; $200 billion in spending power.” Evolve has been advertising Evivo, their infant probiotic product, to women such as Sloane, stating that 9 out of 10 babies born to women such as Sloane need the product now.
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While Evolve’s current target audience reflects the fact that probiotics are trendy among young, affluent people in the West, the Bill & Melinda Gates Foundation had a different customer in mind when it recently co-led a $40 million Series C round for the company. Specifically, the foundation is interested in how Evivo might help infants who suffer from severe acute malnutrition and how probiotics might help malnourished children in developing countries to absorb nutrients and avoid infection.
The financing is just one example of growing interest among investors in the human microbiome, which is made up of more than 100 trillion organisms and performs vital functions from synthesizing vitamins to aiding digestion to helping the immune system develop. Horizons Ventures, the venture arm of the Li Ka Shing Foundation in Hong Kong, led the investment together with the Gates Foundation in hopes of bringing the product from the U.S. to Asia. And as Evolve expands its work globally, it could set a precedent for how the surge of microbiome investments — often focused on addressing overnutrition and obesity — could also have implications for malnutrition.
Research has demonstrated that infant bacterial colonization is critical for immune and gastrointestinal development, and that interventions to restore the composition of the microbiome might help with the treatment and prevention of severe acute malnutrition, which affects 16 million children and kills 3 million each year.
The microbiome is an example of what Bill Gates, the billionaire co-chair of the Gates Foundation, calls a surprising convergence in the research between diseases that largely affect rich countries and those that affect poor countries, where his foundation focuses its global health efforts.
The $40 million Series C funding builds upon conversations between Gates and Evolve that began more than a decade ago, beginning with the Enteric and Diarrheal Diseases Program. In April, the Gates Foundation, Evolve, and the International Centre for Diarrhoeal Disease Research in Bangladesh announced a study to investigate how the infant probiotic could help infants suffering from severe acute malnutrition.
The most recent funding will primarily be used to expand the availability of Evivo in the United States and around the world, while also supporting efforts to develop products for age segments beyond infants, and bringing a microbiome diagnostic test to market.
The Gates Foundation is funding numerous initiatives at the intersection of gut health and global health, including a past grand challenge backing projects that alter pathogens in the microbiome to address newborn and infant gut health, and supporting partners developing microbiome solutions ranging from nutrition-based to fecal transplants.
The Gates Foundation invested in Evolve through its Program-Related Investments team, which looks for opportunities to support companies whose success is directly linked with impact.
“Seeing a company specifically focused on improving nutrition and health outcomes for kids at an early stage of life really synched well with our theory of change in this space, which is focused on really improving the microbiome of kids at an early age in developing countries, with the idea that improving that microbiome can lead to significant health impacts and improvements both in term of preventing enteric infections but also in terms of growth and development,” Ryan Kreitzer, a principal on the PRI team, told Devex.
As the Gates PRI team identifies partners for these early-stage investments, they seek out co-investors who can add value — including corporate venture arms that have advice to offer on clinical development or regulatory issues or corporate expansion. Investors from Evolve’s Series A and B rounds also joined the $40 million Series C round, and new investors in the Series C included the strategic venture capital arm of Johnson & Johnson.
But in order for probiotics to reach the populations that cannot pay, there remains a need for grant funding, said Gregor Reid, chair in human microbiology and probiotics at the Lawson Research Institute, whose work on probiotic fermented food in Africa received funding from the Gates Foundation.
“Once the $40 million is spent, how will the B. infantis [probiotic] continue to roll out for the most needy? I assume there is a plan. Indeed, given the challenges of reaching the people in developing countries who suffer the most, it is not clear to me how Evolve plan to do this and make a profit,” he said.
Reid also said he finds it hard to imagine that “a single Bifidobacterium will solve everything.”
The product that would become Evivo was dreamed up by researchers at University of California Davis studying the composition of breast milk. While studying infants in the Davis area, they found that the children weren’t absorbing 15 percent of the nutrients.
According to David Kyle, chief scientific officer at Evolve, 90 percent of Western babies now lack Bifidobacterium longum subspecies infantis, or B. infantis, which is a strain of good bacteria that protects the infant gut microbiome from pathogenic bacteria and allows babies to absorb nutrients in breast milk. He said this is due to the increased use of infant formula, the rise of Caesarean sections, and the overuse of antibiotics. Comparing data from diapers from 1913 to today, Evolve researchers determined the reason these babies were not absorbing these nutrients was due to the lack of B. infantis in their gut.
“We had the brilliant idea that if nature put it there in the first place, and now it’s gone, we should put it back,” said Kyle.
Evolve sells Evivo, which contains an activated form of B. infantis, in airtight sachets, and mothers use a small mixing bowl to mix the probiotic with their milk, providing it to their babies once daily via a feeding syringe. A study funded by the company demonstrated how the B. infantis takes over the lower intestine, allowing babies to absorb the special nutrients that are otherwise excreted, and also indicated that B. infantis remains colonized in the gut for more than 30 days after being consumed.
What remains to be seen is whether it can also reduce the risks of short- and long-term health conditions including allergies, eczema, asthma, and some cancers, which have been linked to low bacterial diversity in infancy.
“We’ve pretty well characterized our body and physiology, but this is the part that has not been understood,” Timothy Brown, chief executive officer of Evolve, said of the microbiome. “The reason that investors are really intrigued by it is they know it is intimately related with health, and they know some companies — a company, hopefully us — have figured out how to actually control it and modulate the gut, and by doing so influence health.”
On its website, Evolve points to studies that B. infantis remains the predominant colonizer of the infant gut in developing countries. Glenn Gibson, professor of food microbiology at the University of Reading, told Devex he would like to see baseline data comparing a variety of candidate strains before he is convinced B. infantis is the solution to restore the gut to its natural state. But Brown told Devex that demand for infant microbiome products like Evivo are likely to grow as the rates of C-sections, the use of infant formula, and the overuse of antibiotics expands to developing countries.
As Evolve works with the Gates Foundation, Horizon Ventures, and other partners on global expansion, the company will have to navigate what Brown describes as a patchwork of regulatory schemes for probiotics. In the U.S., Evolve used a Food for Special Dietary Use regulatory pathway.
The company will also have to figure out how to price the product, which currently costs about $75 a month, whether that means through insurance plans, ministries of health, or local health care channels and distributors.
A third challenge with global expansion is that the Evivo product must be stored in a refrigerator or freezer. Because a temperature-controlled supply chain would be prohibitively difficult in some parts of the world, Evolve hopes to work with the Gates Foundation on ways to move the product out of the cold chain so that it can sustain warmer temperatures.
The investment in Evolve may be the sign of more to come, particularly as Gates said it is becoming increasingly clear how the gut microbiome factors into the development and survival of children.
“We know that children in poor countries who are malnourished and vulnerable to enteric infections have underdeveloped microbiomes that weaken their immune system and make them more susceptible to disease and to impaired brain development that lasts a lifetime,” he said at the 2018 J.P. Morgan Healthcare Conference in San Francisco, California, in January.
Children in wealthy countries who grow up in superhygienic environments, with processed foods and antibiotics, are more susceptible to obesity, autoimmune diseases, diabetes, and hypertension due to their poor gut health, Gates continued.
“The solution in both instances is making sure that kids have the right constellation of microbes in their gut — and that they’re eating the right foods to support a healthy microbiome,” he said.
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