If the start of 2017 is any indication, the microbiome field—which aims to turn human gut bacteria and other body microorganisms into therapies—is thriving on various levels.
On the academic front, Penn State announced Feb. 2 its creation of a new center for microbiome research, joining dozens of other academic institutions exploring the field’s potential.
On the commercial front, Janssen Human Microbiome Institute, a part of Johnson & Johnson, announced, also on Feb. 2, several new collaborations with Caelus Health, DayTwo and others in efforts to find microbial therapeutics that are able to target metabolic diseases. The aim is to learn how to leverage the microbiome for pre-diabetes and Type 2 diabetes, broadening Janssen’s microbiome portfolio beyond inflammatory bowel disease and immuno-oncology.
In January, a panel of biotech executives at the Biotech Showcase, nearby the J.P. Morgan Conference in San Francisco, discussed the value of the microbiome and the Food and Drug Administration’s work with companies in the space to develop a clearer regulatory pathway.
It appears to be part of a rapid turnaround in a field that suffered a significant setback last summer when Seres Therapeutics, the first publicly held microbiome-focused company, had a major clinical trial failure for its fecal transplant aiming to treat recurrent Clostridium difficile (C. diff.) infection. The company’s stock plummeted by 76% as a result and stirred up skepticism.
Seres, which went public in June 2015, is trying to get back on track. The Cambridge, Mass.-based company said Jan. 31 that findings from its analysis of its SER-109 phase 2 study failure suggest that misdiagnosis of some patients, and possible suboptimal dosing in others, contributed to the outcome. Seres said it is involved in ongoing discussions with the Food and Drug Administration about starting a new, redesigned clinical trial for SER-109.
While microbial cells, numbering in the trillions, represent half of the human’s biological system, research into their value only began about a decade ago, said Dirk Gevers, global head of the Janssen Human Microbiome Institute. "The past 100 years focused on a couple dozen pathogenic organisms triggering disease…but now people realize other organisms have a more subtle or even beneficial way of interacting with us," he told BioPharma Dive.
It is not only a private-sector effort. The National Institutes of Health’s National Human Microbiome Project is using its data repository to look for correlations between changes in the microbiome and human health.
"The field is very young and we’re just starting getting things into the clinic," Gevers said, adding that the ability to try fecal transplants, dietary interventions and personalized nutrition plans to leverage the microbiome makes the approach promising.
Yet Gevers said he is seeing explosive growth in the therapeutic microbiome field: By his count, more than 40 different academic institutions in the U.S. and Europe, including NYU, Penn and Stanford, are involved in interdisciplinary microbiome research. Clinical research is very active: "We counted close to 400 different clinical studies looking at the microbiome and its impact on health," he said.
With C. diff. alone, there have been at least 18 different studies backing the potential of various microbiome therapies—not necessarily in the way Seres has approached it—and showing a 90% efficacy rate, Gevers said. He added he anticipates that Seres will redo its trial, "and I think they’ll come out in a much better position."
As for microbiome-focused business initiatives, Johnson & Johnson inked a licensing agreement with Vedanta Biosciences in January 2015 to develop its lead microbiome candidate, IBD drug VE202, in a deal that could surpass $241 million.
Moreover, Janssen already has interacted with about 70 start-ups in the U.S. and Europe, Gevers said, "and it just started a few years ago. But the findings are so exciting it triggers investment…More than $1 billion is invested in [microbime] start-ups right now."
Currently, interest in the microbiome space is starting to be translated into products under clinical development, Gevers said. Numerous potential therapies are in Phase 1, with other candidates in Phase 2 and Phase 3, including multiple trials targeting C. diff. infection (which he characterizes as "one of the lowest-hanging fruit"), as well as studies into treating irritable bowel syndrome, urinary tract infections and more.
Synthetic Biologics, for example, has two phase 2 product candidates in its microbiome pipeline: SYN-004 (ribaxamase), an oral enzyme tablet, for treating C diff. infection and antibiotic-associated diarrhea; and SYN-010 for treating IBS with constipation.
When the Janssen Human Microbiome Institute was created two years ago, Gevers said, "We began with an open mind, but we decided not to limit it to our own research," instead forming external partnerships "to help accelerate entrepreneurs’ solutions."The institute also is involved in academic partnerships with Mount Sinai and others, he noted.
According to Gevers, immuno-oncology in general is "a strong area to go next."
Indeed, in November 2016 Bristol-Myers Squibb and Enterome, a French company, entered into a microbiome deal focusing on immunotherapies. A bit earlier, Bristol-Myers had announced a five-year partnership with Johns Hopkins University to evaluate, in part, how the microbiome contributes to anti-tumor activity.
And in April 2016, Pfizer and Roche led the Series B financing for microbiome research company Second Genome that totaled nearly $43 million.
Yet, while the microbiome has drawn the interest and dollars of pharma's biggest players in recent years, market analysts make it clear that most of the innovators in the field are smaller start-ups and early-stage biotech companies – and the market could reach $1 billion in the next decade or so.
Dramatic market potential
To a large extent, "it’s the small fish" doing the early-stage microbiome groundwork, said Michael Darcy, a business insights analyst with Decision Resources Group, a life sciences market research firm.
Darcy sees dramatic market potential for microbiome-based therapeutics. But he said he expects gradual growth even if microbiome products make it to the clinic because of the significant learning curve for physicians as compared to traditional drugs.
While there are hurdles even after a commercial entrance, excitement could drive the market, he added.
Darcy said microbiome-focused therapies for C diff. recurrence likely will reach the clinic sooner than other potential applications, "because so much work has been done already and it’s already been shown to work." Clinical output from products for gastrointestinal, metabolic and neurological disorders might be at least another five to 10 years out, he added.
He points to Seres, which had a market cap of $1.2 billion based on Phase 1 data only and then lost most of its market value after SER-109’s early slip-up, as showing "there’s promise, but also volatility…because nobody knows how these companies will perform."
"The market value could skyrocket if any products show promise [but] this first setback shows the sensitivity of investors," Darcy said. Venture capitalists, however, still believe in the microbiome field’s potential and are putting money behind it, he said.