Overview

HUMAN MICROBIOME

The human microbiome is the community of bacteria and microorganisms that lives in association with the human body. Thought to outnumber human cells by nearly 10 to 1, the microbiota resides on human tissue or in body fluids, particularly in the gastrointestinal tract.

Although the microbiome has been poorly understood in the past, it has recently been recognized by the medical community for the vital role it plays in promoting human health. Through the significant efforts of the NIH Human Microbiome Project and the White House National Microbiome Initiative, we have begun to appreciate the multitude of beneficial roles microbes play in human health, including regulating metabolic function, stimulating the immune system, protecting against disease and more. As such, dysbiosis, or disruption of the healthy microbiota, caused by antibiotics, diet or other factors, can contribute to a variety of diseases that require novel treatments.

CLINICAL MICROBIOTA DEVELOPMENT

Crestovo is closely linked to the origins of clinical microbiota applications, which can be traced back to 1988 when our founder and scientific advisor, Dr. Thomas Borody, pioneered what is now called ‘fecal microbiota transplantation’ (FMT) to harness the human gut microbiome to treat gastrointestinal conditions. The FMT procedures originally included transplant of stool from a healthy donor to restore the microbiome in a patient suffering from a dysbiosis-driven disease whereby they lack beneficial bacteria, typically as a result of antibiotic treatments. Historically, FMT methods have involved invasive techniques, including retention enema, nasogastric tube, colonoscopy or self-administered enema. Dr. Borody’s team has performed over 12,000 FMTs since 1988.

Crestovo’s scientific collaborators, Drs. Alexander Khoruts and Michael Sadowsky, have been pioneers in moving clinical microbiome applications forward. In 2014, they invented the first orally-administered microbiota formulation and conducted a clinical study in recurrent Clostridium difficile infection (CDI),which saw the successful prevention of recurrence in 43 of 49 patients.

Crestovo’s Full-Spectrum Microbiota™ (FSM™) platform builds on these principles of microbial diversity by establishing a class of novel therapeutics that utilizes a highly refined, encapsulated pharmaceutical composition.

A 2014 proof-of-concept study led by Drs. Alexander Khoruts and Michael Sadowsky at the University of Minnesota developed a leading early-stage formulation of a Full-Spectrum Microbiota™ (FSM™) preparation.  The study demonstrated success in 43 of 49 patients with recurrent CDI (88% success rate), defined as no recurrence of CDI over two months.  Furthermore, patients’ microbial communities achieved near normalization within one month following treatment.

Crestovo’s lead, proprietary FSM™ candidate, CP101, is a capsule taken orally to deliver a healthy microbiota into a patient’s gastrointestinal tract to treat disease. CP101 is currently in a clinical trial, PRISM 3, for patients with recurrent CDI.

REFERENCES

Burden of Clostridium difficile infection in the United States. Lessa FC et al. N Engl J Med. 2015 Feb 26; 372(9): 825-34.

Clostridium difficile Infection. Leffler DA et al. N Engl J Med 2015; 372: 1539-1548.

Duodenal infusion of donor feces for recurrent Clostridium difficile. van Nood E et al. N Engl J Med. 2013 Jan 31; 368(5): 407-15.

Fecal microbiota transplant for recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience. Patel NC et al. Mayo Clinic Proc 2013 Aug; 88(8): 799-805.

Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Drekonja D et al. Ann Intern Med 2015 May 5; 162(9): 630-8.

Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Kassam Z et al. Am J Gastroenterol. 2013 Apr; 108(4): 500-8.

The Long-term Efficacy and Safety of Fecal Microbiota Transplant for Recurrent, Severe, and Complicated Clostridium difficile Infection in 146 Elderly Individuals. Agrawal M et al. J Clin Gastroenterol. 2016 May-Jun; 50(5): 403-7.