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MicroBiome Therapeutics                                                                                                                                                                                    (212) 584-2276
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—Recent Publication Shows Metformin Improves Glycemic Control by Modulating the Gut Microbiome and Triggering Specific Cellular and Immune Mechanisms—
—MBT’s Microbiome Modulator Is in a Pilot Trial as Adjunctive Therapy to Reduce Metformin- Induced GI Side Effects and Improve Blood Glucose Control—
—Data to be Presented at ICE/ENDO 2014 Show MBT’s Microbiome Modulator NM504 Improves Blood Glucose Control and Increases Insulin Levels in Prediabetes and Diabetes—

Broomfield, CO – June 17, 2014 – MicroBiome Therapeutics™ LLC, (MBT) today reported that a recently published scientific study shows that the diabetes drug, metformin, alters the bacterial populations in the gut in favor of a bacterial species that exerts specific cellular and immunological effects, resulting in improved glycemic control. This is the first study to demonstrate a link between metformin and changes in the gut microbiota and it provides insights into the possible mechanism of action of NM504 and NM505, MBT’s lead microbiome modulators in clinical development for diabetes and prediabetes. Metformin is a first-line treatment for type 2 diabetes and the seventh most prescribed drug in the US.

The new study, recently published in the journal Gut¹, showed that metformin treatment significantly improved the glycemic profile of mice that became obese after receiving a high fat diet. Researchers also showed that metformin induced a change in the composition of the GI microbiota in these mice, increasing the population of a bacterial strain known as Akkermansia. Akkermansia acts to increase the number of goblet cells in the gut. These produce protective mucous that helps keep the lining of the intestinal tract healthy and functional. In these mice, Akkermansia also affected certain immune responses, stimulating the production of regulatory T-cells that act to reduce the prevalence of fat cell-generated pro-inflammatory cytokines, which are associated with obesity and glucose intolerance.

To confirm the role of Akkermansia in producing these beneficial effects, the researchers administered Akkermansia to the obese mice in place of metformin. Akkermansia alone produced a similar improvement in glycemic control. The authors concluded that increases in Akkermansia may constitute a novel mechanism for the antidiabetic activity of metformin and that pharmacological modulation of the gut microbiome could offer new ways to treat type 2 diabetes.

“This elegant study, the first to demonstrate a link between the antidiabetic efficacy of metformin and changes in the gut microbiome, may offer insights into why the pilot study testing our microbiome modulator, NM504, in combination with metformin produced an unexpectedly large drop in blood glucose levels beyond what had been achieved with metformin alone,” noted Steve Orndorff, PhD, CEO of MicroBiome Therapeutics. “We look forward to sharing the results from our NM504/metformin clinical study, which are expected shortly.”

MBT’s microbiome modulator, NM504, is in a confirmatory proof of concept clinical study testing its ability to improve blood glucose levels and decrease gastrointestinal side effects in type 2 diabetes patients taking metformin. In a published case report², co-administration of NM504 eliminated the dose-limiting diarrhea caused by metformin in a metformin-intolerant patient with newly-diagnosed diabetes and produced additional large decreases in his highly elevated blood glucose levels. Based on its work with NM504, MBT has developed a reformulated version of metformin called NM505, which combines metformin with proprietary microbiome modulators. The company is preparing to launch a clinical study testing the ability of NM505 to improve metformin tolerability and reduce the dose-limiting GI side effects commonly associated with metformin use.

MBT is also developing microbiome modulator NM504, which alters the GI microbiome to enhance insulin sensitivity and glycemic control in individuals with prediabetes and diabetes. The company previously reported top-line results from a double-blind, randomized, placebo-controlled trial showing that oral administration of NM504 alone significantly reduced postprandial serum glucose levels and increased insulin sensitivity in subjects with prediabetes and untreated type 2 diabetes. In this study, NM504 was well tolerated. More complete data from the NM504 study will be discussed in a podium presentation at the upcoming ICE/ENDO 2014 meeting in Chicago, Illinois.

MBT’s evidence-based microbiome modulators are designed to alter bacterial populations and their environment in the GI tract to treat and prevent serious health conditions. MBT’s microbiome modulators act on multiple factors, providing selective substrates that augment the growth of targeted desirable bacterial strains and discourage the growth of others that may be harmful. These shifts in the GI microbiome have the potential to have a major impact on factors affecting metabolism and weight.

Dr. Mark Heiman, CSO, will discuss the results of the NM504 clinical study in a podium presentation at ICE/ENDO 2014, the joint meeting of the International Society of Endocrinology and The Endocrine Society.

Session: Type 2 Diabetes: Beta Cell Function and Novel Interventions
Date: Monday, June 23, 2014, McCormick Place West; 11:30 AM – 1:00 PM CT
Title: OR40-5 abstract, number 14546 – Improved Oral Glucose Tolerance in Prediabetics and Type 2 Diabetics in a Pilot Clinical Trial Testing a Novel Gastrointestinal Microbiome Modulator.

1 – An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice”, Na-Ri Shin, June-Chul Lee, Hae-Youn Lee, Min-Soo Kim, Tae Woong Whon, Myung-Shik Lee, Jin-Woo Bae, Gut 2014;63:727–735, doi:10.1136/gutjnl-2012-303839     http://gut.bmj.com/content/63/5/727.full.pdf+html?sid=e07f016c-8cd7-4f28-a422-dc9524b3b834

2 – A novel cobiotic containing a prebiotic and an antioxidant augments the glucose control and gastrointestinal tolerability of metformin: a case report, F. Greenway, S. Wang, M. Heiman, Beneficial Microbes, DOI -10.310.3920/BM2012.0063, http://wageningenacademic.metapress.com/content/FG7642372U410742

About MicroBiome Therapeutics™

MicroBiome Therapeutics LLC (MBT) is a clinical stage biotechnology company developing drug therapies that aim to improve health status by interacting with and altering the human microbiome. MBT is developing microbiome modulators for metabolic diseases. NM504 is being tested in clinical trials for the management of insulin sensitivity and blood glucose levels in prediabetic and obese individuals, and NM505 is a reformulation of metformin incorporating microbiome modulators for type 2 diabetic patients who are metformin intolerant. For more information, visit www.mbiome.com.