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FURTHER ADVENTURES IN OUR INNER SPACE

The most recent Biotech Primer WEEKLY looked at a particularly productive new area of medicine courtesy of our own tiny personal zoo: the microbiome. We considered how resetting a person’s microbiome with a fecal matter transplant (FMT) aka bacteriotherapy can heal such troubling conditions as antibiotic-resistant C. difficile infections and inflammatory bowel disease (IBD).

Thankfully for the millions suffering from these health conditions, acceptance of FMTs is growing. Now the research community is turning its attention to the specific components behind the microbiome’s healing potential. Several biotech companies are already developing more precisely-defined therapeutics. This work will foster better quality control and more comfortable formulations. Who wouldn’t prefer swallowing a capsule to undergoing an enema or colonoscopy?

SOMETIMES IT TAKES A LITTLE BITTY VILLAGE

Vedanta Biosciences (Cambridge, MA) is taking the “consortium“ approach. Their researchers are looking at specific bacterial strains or clearly defined communities of strains (i.e., consortia) that will likely benefit certain medical conditions. Vedenta will then isolate these specific “bugs” for development as standardized therapy. In broad strokes, here’s how:

  • Collect clinical data from studies that investigate the human gut microbiome
  • Identify bacterial communities associated with good clinical responses
  • Test these strains and select those with the most potent pharmacological affects
  • Assemble the selected strains in consortia that work well together
  • Use the chosen strains to make GMP-grade drugs for clinical studies

Vedanta’s lead candidate, orally-administered VE303, is in Phase I clinical testing for C. difficile infection. In addition, Finch Therapeutics (Somerville, MA) and Seres Therapeutics (Cambridge, MA) both have consortium-containing capsules targeting C. difficile infection in clinical development (Phase II and III, respectively).

MONOCLONAL MICROBIALS

Evelo Biosciences (Cambridge, MA) has coined the term “monoclonal microbials” for its somewhat different approach. Their researchers have identified one (mono) specific bacterial strain that promises to modulate patients’ immune response. The lead candidate, EDP1066, is currently in Phase I clinical studies of psoriasis and atopic dermatitis.

BACTERIAL BYPRODUCTS WITH BENEFITS

South San Francisco-based Second Genome zeros even further in, microbiomically speaking. Its scientists have isolated a bacterial byproduct—a protein or small molecule secreted by the bacterium that packs a therapeutic punch.  Their lead candidate, small molecule SGM-1019, which is preparing to enter Phase II clinical studies for both inflammatory bowel disease (IBD) and nonalcoholic steatohepatitis (NASH), a severe type of liver disease. The company also has a microbiome-derived protein in preclinical development for IBD.

CANCER VERSUS BACTERIA, VIRUSES & FUNGI?

Intriguingly, some research suggests that modulating the microbiome may even help induce the immune system to fight cancer. Seres Therapeutics and Vedanta are both conducting preclinical research in this area.

MICROBIOMIC BENEFITS FROM THE BEGINNING

Researchers clearly have their scrupulously clean hands busy exploring the health benefits that our teeny tiny zoo may someday yield.  However, some of this research provokes more controversy than others. For example, studies show that babies delivered by C-section have about 20% higher rates of asthma than do those born vaginally. C-section babies are also significantly more likely to develop allergies than their traditionally-born peers. It’s now thought that the higher risk of these health problems may stem from the fact that C-section births fail to give newborns the protective bacteria that comes from passing through the birth canal.

Of course, doctors prescribe C-sections in many cases. What’s a mother to do about her child’s microbiota? Enter a procedure called vaginal seeding, wherein the obstetrician transfers some of the mother’s microbiota (found in her vaginal fluids) to her child’s mouth, nose, and skin using a cotton swab. Preliminary studies suggest that this practice partially endows C-section newborns with some of their mother’s protective microbiota. Whether or not the post-birth swipe translates into long-term benefits remains to be seen. There are also potential risks involved, so the procedure is still considered experimental.

Most microbiomic treatments in clinical development focus on C. diff infection or inflammatory bowel diseases. However, scientists believe that the microbiome influences many other aspects of human health, including allergies, asthma, autism, Parkinson’s disease, depression and anxiety, obesity, and diabetes. For an overview of the “gut-brain axis” and its health implications, check out this past WEEKLY.  We’re eager to see what the companies exploring the body’s inner space as microbiomic treatments travel from preclinical to clinical stage research do next. Think about it—coming to a drugstore near you someday—poop in a pill!

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