Finally, an IBD microbiome drug goes to clinical trial

Summary:  Seres Therapeutics began its Phase 1b placebo controlled clinical trial on Dec 14, 2015, for SER-287, which is the first drug aimed at the microbiome for a non-infectious, chronic condition, ulcerative colitis (UC).  This is the first IBD microbiome drug that actually targets the constituents of the microbiome. This approach treats chronic disease without suppressing  the body’s immune response. Instead, specific strains of bacteria are introduced that re-balance the billions of different types of bacteria that are in the digestive tract, which then increases immunity and manages the disease.  Instead of being immunosuppressive, this treatment targets the root cause of UC  which is gut dysbiosis, increasing immunity. SER-287 clinical trial is currently recruiting participants if you are interested; contact information is below.

Note:  The immune system outsmarts anti-TNF meds a lot of times — 30 to 80% of the time for IBD.  Isn’t that a crazy broad failure range?  This post speaks to some of the whys of that failure.  And… realize a lot more diseases use these immunosuppressive meds beyond IBD.

I wrote about the immunosuppressant and biologic microbiomes not looking ‘healthy’ in this post, and in fact had the opportunity to have that very question answered and confirmed by Johns Hopkins GI expert Dr. Gerard Mullin, MD at the Evolution of Health Functional Forum, called Microbiome Maximized Medicine, held in NY on October 5, 2015.  The YouTube of that dialogue can be linked to on this post.

These disease microbiome drugs are not immunosuppressive, rather their mechanism of action is to enhance and increase immunity.

Incidentally, healing diets also introduces microorganisms and food substrate matter into the gut that cause mucosal healing with increased immunity to manage chronic disease

I wrote about the microorganisms we ingest at: AVG NUMBERS AND KINDS OF MICROORGANISMS CONSUMED IN A DAY.  Interestingly, the USDA dietary pattern had the highest total microorganisms for the day, due to yogurt and cottage cheese consumption, whereas the AMERICAN and VEGAN dietary patterns had 3 orders of magnitude fewer total microorganisms primarily due to heating probiotic type food such as cheese (which kills microorganisms) or the diet lacks consumption of probiotic type foods.  I am certain the FODMAP type foods omitted or ingested also impact microbiome richness since these food substrates are food for bacteria which if provided, will accordingly bloom bacteria. See here for a FODMAP post. Healing diets contain unheated live fermented foods and tolerable FODMAPS and have been shown to increase microbiome diversity and immunity in compromised guts.  See this post for IBD: 50 IBD SCD REMISSION PATIENTS: RUSH PAPER.

“Bugs as drugs” idea for disease treatment

Startups are harnessing the trillions of bacteria inside us to eradicate chronic disease such as diabetes, obesity, arthritis, MS, autism, depression, and more. This “bugs as drugs” idea for disease treatment packages live strains of bacteria originating from a healthy donor’s microbiome to be used as therapy.

This all began as a fecal microbial transplant (FMT) which is currently approved for antibiotic resistant CDiff infection and has over 90 percent cure.  A startup that  provides FMT substrate matter originated out of a not-for-profit from MIT and is called OpenBiome.  Mark Smith is OpenBiome’s founder who considers that the oral application wouldn’t just reduce the discomfort of the FMT transplant, but that swallowing a capsule of someone else’s healthy digested material — [that’s where the live strains of bacteria are coming from] or eventually swallowing strains cultivated in a lab,—could become a maintenance therapy for sufferers of a variety of gastrointestinal disorders, and for that, “We’re in the testing and evaluation phase.”  Side bar:  Anecdotal evidence from my follow of numerous DIY groups does lean towards needing repeat FMT for some diseases. Diet impact post-FMT microbiome is not well understood (nor is it understood pre-FMT for the donor) which could impact acceptance of the transplanted microbiome sooner.

FMT are not the way of the future. They are just a transitional solution… [for OpenBiome’s capsule, the first patient to test will be] a quadruple amputee with C. diff. She’s not a good candidate for a fecal transplant, but her doctor thinks this pill might be perfect.” MIT Lab Hosts Nation’s First Stool Bank, But Will It Survive? and WHAT’S LURKING IN YOUR MICROBIOME? POSSIBLY, A CURE FOR DISEASE

Why start with IBD for “bugs as drugs”?

The short of it is, they are picking diseases with known causation being gut dysbiosis; there is a difference with correlation and causation.  “If you’re going to leverage the microbiome for drug discovery, it’s not the correlations that matter. It’s the causal relationships. How are the bacteria interacting with the host in a way that’s driving our biology? Did patients with bowel or intestinal diseases—colitis, for instance—have different gut bacteria profiles because they were ill? Or were they ill because they had different gut bacteria profiles? For example, children with autism often have significant gastrointestinal problems. Yet is that a reason for their autism, or is it just a related fact?”    -WHAT’S LURKING IN YOUR MICROBIOME? POSSIBLY, A CURE FOR DISEASE

The diseases in the right quadrant represent those with known causation as microbiome dysbiosis. Left quadrant diseases have been associated with gut dysbiosis.  DiLaura, of Second Genome, explains, “So our efforts, right now… aims to create a drug for IBD. Difficult as that sounds, it is a modest goal compared to the company’s second order of business: create a drug for metabolic diseases like type 2 diabetes. The first drug, if effective, could affect hundreds of thousands of people; the second, millions”. -WHAT’S LURKING IN YOUR MICROBIOME? POSSIBLY, A CURE FOR DISEASE

Background on Seres medicines

All of Seres’ medicines are made up of  biologically-sourced bacterial spores (which are very different from fungal spores) which can be collected in a capsule for easy administration.  

The first drug candidate from Seres to reach clinical trials is for treatment of Clostridium difficile infection (CDI) in adults; this drug. SER-109, is now in Phase 2 trials and is a mixture of bacterial spores from 50 bacterial species taken from healthy donors.  Currently, FMT is used to treat recurrent antibiotic resistant CDI with over 90 percent cure.

SER-287 is the second Seres drug joining alternative capsule treatment for FMT but this time for UC. SER-287 is a microbial cocktail capsule containing “a complex and diverse bacterial spore ecology.

I am concluding the specific microbial composition of SER-287 is sourced from healthy donors as is SER-109; the trial is looking at engraftment of SER-287 bacteria into the intestinal microbial community. Ordinarily, commercial probiotic bacteria such as in yogurt, does not engraft into the microbiome.  These bacteria are transient and repeated consumption is required to maintain and sustain benefit.  Benefit often ceases about 3 days post consumption.

If you want further detail on Seres, see Seres therapeutics website.

Clinical Trial details for SER-287, the first IBD microbiome drug that targets the microbiome

The link to the study is: A Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Ulcerative Colitis.  About 55 patients are expected to enroll; the trial is currently recruiting participants.  The drug used, SER-287, treats UC without suppressing the body’s immune response. Instead, SER-287 delivers specific strains of bacteria to re-balance the billions of different types of bacteria that are in the digestive tract, which then manages the disease.  This treatment is not immunosuppressive; instead it targets the root cause of UC which is gut dysbiosis.

The current standard of care for UC treatment uses drugs that suppress the immune system to reduce inflammation in the colon and rectum which makes patients susceptible not only to infectious diseases, but to cancers that would otherwise be killed off by the immune system.

Primary Outcome Measures of the Clinical Trial:
  • Safety and tolerability of SER-287 vs. placebo in adult subjects by analysis of AE’s, lab values, vital sign, physical exam findings, medical history, and ECG.
  • Examination of baseline composition of the intestinal microbiome to the composition. Changes in the composition of the microbiome will be characterized by rDNA 16S V4 genomic data sets. Changes will be assessed by total number of unique bacteria and microbial composition.
  • Engraftment of SER-287 bacteria into the intestinal microbial community. Microbiome will be characterized by rDNA 16S v4 Genomic Data Sets. Engraftment will be assessed as the outgrowth of bacteria that compromise the SER-287 spore ecology in the subjects GI tract post treatment.
The time frame for the study

December 2015 to June 2017.

Contact for the study

Michele Trucksis, PhD, MD at  clinicalstudies@serestherapeutics.com

Study Locations are:
  • United States, Florida.  Advanced Gastroenterology Ctr, Port Orange, Florida, United States, 32127.  Contact: AMMAR HEMAIDEN, MD    386-763-4920
  • United States, Maryland. Capital Digestive Care, LLC – Metropolitan Gastroenterology  Group (MGG), Chevy Chase, Maryland, United States, 20815. Contact: ROBERT HARDI, MD    240-737-0085.
  • United States, Massachusetts. Community Clinical Research Network, Marlborough, Massachusetts, United States, 01752. Contact: JOHN CURRAN, MD    508-320-9248
You can read more about Seres and SER-287 here:

CEO: Seres Therapeutics ‘walks into flying’ with new trial in ulcerative colitis:

As to why they are targeting UC and not a larger population affected condition such as Type 2 Diabetes or Metabolic Syndrome:  Pomerantz, CEO of Seres explained, “As someone who’s worked on eight infectious disease drugs, I know that you want to walk into flying. You don’t want to fly into flying.”  Seres intends to target metabolic diseases in addition to inflammatory and infectious ones, but other recent microbiome startups are looking even further, at fields like autism or others. Pomerantz maintains that while such diseases may be in the realm of those which can be treated by rebalancing the microbiome, “we don’t think that was smart” to start with them.

On future of Doctors getting a better sense of what’s living inside their patients

From WHAT’S LURKING IN YOUR MICROBIOME? POSSIBLY, A CURE FOR DISEASE:  In the not-too-distant future an annual physical will include not only a blood and urine test but a gut microbiome analysis, too. That could rapidly transform microbiomial testing into an enormous global business.

Current disease epidemics including obesity, diabetes, asthma—relate to how crucial parts of our gut microbiomes have been wiped out by the overuse of antibiotics or (in many cases) an over reliance on C-section births, which appear to deprive newborns of crucial bacteria.

Blaser foresees a standard medical protocol where a newborn will receive “missing” bacteria early in his life, and where any patient undertaking a course of antibiotics might also receive a bacterial remedy—or perhaps the kind of remedy Second Genome [or Seres] is creating—to mitigate the damage.

On future of biotech looking at microbiome

The typical road to success for a biotech startup is not so much an IPO as an acquisition by a large pharmaceutical company; given the complexity and expense of drug trials and marketing, it is usually too difficult to stay small and independent. Iyer believes that within a few years, there will be a consensus that “any therapeutic area, if not every therapeutic area, and every effort to understand the biological mechanism of disease, has to involve the microbiome.” When that time comes, he adds, “no pharma company will want to live without this capability.” -WHAT’S LURKING IN YOUR MICROBIOME? POSSIBLY, A CURE FOR DISEASE

lightbulb1Well.. what can I say?  You knew  disease microbiome drugs was coming.  Well… perhaps it is here.  

But, again I repeat, without diet considerations post IBD microbiome drug treatment, that microbiome likely will not sustain without repeat IBD microbiome drugs.  This is because the environmental triggers remain for relapse for chronic disease.

And… also bearing repeat:  Healing diet can modulate the chronic diseased microbiome to manage the disease.  This is always worth a first try.

Last updated: March 22, 2016 at 21:27 pm for SEO optimization.

In health through awareness,

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4 thoughts on “Finally, an IBD microbiome drug goes to clinical trial”

  1. I enjoyed reading your discussion of the IBD microbiome drug currently being tested.
    Sinusitis (especially chronic sinusitis) is another illness that will definitely be treated with bacteria in the future. Abreu et al (2012) found that chronic sinusitis sufferers had microbiomes that were “out of whack” and were missing Lactobacillus sakei (due to years of antibiotics).
    Ingesting foods with Lactobacillus sakei (found in Korean fermented kimchi and other foods) does not appear to treat sinusitis, but smearing/dabbing/snorting a Lactobacillus sakei mixture in the nostrils results in the bacteria traveling up to the sinuses and treatment of the sinusitis (this is similar to what Abreu et al did in a mice experiment). Typically a person starts to feel better within hours.

    This method successfully treated my family (4 members) of chronic sinusitis almost 3 years ago (and acute sinusitis since then), and a number of people have written me about their similar successes with Lactobacillus sakei. In fact, I initially started a site lactobacto.com to publicize my family’s results, as well as developments in microbiome (and health) research to the general public.

    It is my understanding that the original researchers (Abreu et al) are now testing in clinical trials a nasal spray containing L. sakei and other bacteria for sinusitis.

    1. Hi. I applaud your efforts! I am always interested in anecdotal evidence of the power of probiotics. I am hoping that you can share a link that shows what is in Kimchi… bacteria wise. I tried to find such on your website but could not. On a side-note: a friend just returned from Korea and reported back that kimchi was served at every meal there; sometimes it was heated. In that regard, I will note the Dr. Rob Knight, in a Reddit, spoke that probiotics, even dead, seem to help modulate the microbiome.

  2. Drugs targeting the microbiome coming so soon. This is definitely headed in the right direction but I agree with you as far as the diet goes. Diet modifications would have to made in order to sustain healing the microbiome

Now I'd like to hear your thoughts... comments are always welcome!