Fecal transplants are most commonly used to cure infections of Clostridium difficile—a weedy bacterium that causes severe, recurring diarrhea. The idea is that a donor’s microbes would reset the recipient’s diseased community, much like re-turfing a lawn that’s overrun by dandelions.

It sounds unorthodox but it clearly works. There are hundreds of stories of miraculous recoveries. And in one clinical trial, fecal transplants cured 94 percent of C-diff patients, while a standard antibiotic cured just 27 percent. Backed with such strong evidence, the technique has become increasingly accepted—a seemingly fringe treatment that is working its way into the mainstream.

Still, there are problems. Fecal transplants are undeniably gross. They can spread pathogens, so doctors typically put potential donors through rigorous screening. And poop is a medicine unlike any other: a largely uncharacterized community of microbes, viruses, and other constituents that varies greatly from donor to donor. This variability causes headaches for regulators—how do you approve a product that comes out of human backsides rather than manufacturing plants, and so changes every time it is produced?

There are two main solutions. The first is to freeze the stools from only the healthiest of donors, store them in stool banks, and use them repeatedly. That’s the approach used by the non-profit organization OpenBiome, as well as facilities in various U.S. hospitals. The second approach is to concoct stool substitutes—cocktails of gut microbes that can replicate the benefits of a fecal transplant, but without the feces.

Several companies are going down the latter route, including Seres Therapeutics, a startup based on Cambridge, Massachusetts. Their lead product—SER-109—consists of a single capsule containing 100 million spores from 50 species of gut microbes, purified from the stools of healthy human donors. It’s designed to treat multiply recurring C-diff infections.

It seemed promising. As Nidhi Subbaraman wrote for Buzzfeed, Seres was a “favorite among a crop of young ventures making drugs containing bacteria.” In September 2014, the company announced that in an early Phase 1b trial, which focuses on safety, SER-109 had cured 29 out of 30 patients with recurring C-diff. In June 2015, the U.S. Food and Drug Administration (FDA) gave the drug breakthrough status—a label intended to accelerate the approval of especially promising therapies.

But last Friday, those early hopes were dashed when Seres revealed that SER-109 had pooped out of a phase 2 trial (which focuses on efficacy as well as safety).

The company had enrolled 89 patients with C-diff infections that had recurred at least three times, and randomly assigned them to either SER-109 or a placebo. Critically, neither doctor nor patients knew which treatment they were getting—a rarity for fecal transplant trials. If it had worked, it would have been a big milestone. But after eight weeks, the patients who got SER-109 were just as likely to have suffered another bout of C-diff as those who got the placebo, and just as likely to have experienced diarrhea, abdominal pain, and flatulence.